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This report is written by MaltSci based on the latest literature and research findings

How do bacteria develop biofilm formation? ​

Abstract ​

Biofilm formation is a prevalent phenomenon in various bacterial species, marked by the aggregation of cells within a self-produced extracellular matrix comprising polysaccharides, proteins, and nucleic acids. This structure enables bacteria to adhere to surfaces and form stable communities, which provide significant advantages, such as increased resistance to environmental stressors and enhanced tolerance to antimicrobial agents. Biofilms are implicated in numerous critical issues across multiple domains, including medicine, industry, and environmental science, particularly in chronic infections associated with antibiotic resistance. Understanding the mechanisms of biofilm development is crucial for addressing these challenges. Research indicates that biofilm formation occurs in distinct stages: initial attachment, maturation, and dispersion. The initial attachment phase involves the adhesion of planktonic bacteria to surfaces, influenced by physicochemical factors and surface properties. Maturation leads to complex three-dimensional structures that enhance nutrient exchange and communication among cells. The dispersion phase allows cells to leave the biofilm and colonize new environments, perpetuating infection cycles. Recent advancements in molecular biology and bioinformatics have shed light on the genetic and environmental factors that govern biofilm development, highlighting the roles of key regulatory genes and environmental conditions. This review synthesizes existing literature on biofilm formation mechanisms, genetic regulation, environmental influences, and implications for infection control and treatment. By identifying gaps in knowledge and emerging technologies, this review aims to contribute to the advancement of biofilm research and its applications in medicine and beyond.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Mechanisms of Biofilm Formation
    • 2.1 Initial Attachment
    • 2.2 Maturation of Biofilm Structure
    • 2.3 Dispersion of Biofilm Cells
  • 3 Genetic Regulation of Biofilm Development
    • 3.1 Key Genes Involved in Biofilm Formation
    • 3.2 Role of Quorum Sensing in Biofilm Regulation
  • 4 Environmental Factors Influencing Biofilm Formation
    • 4.1 Nutrient Availability
    • 4.2 Surface Properties and Topography
    • 4.3 Physical and Chemical Stressors
  • 5 Implications for Infection Control and Treatment
    • 5.1 Challenges in Treating Biofilm-Associated Infections
    • 5.2 Strategies for Biofilm Disruption
  • 6 Future Directions in Biofilm Research
    • 6.1 Emerging Technologies for Biofilm Study
    • 6.2 Potential Therapeutic Approaches
  • 7 Summary

1 Introduction ​

Biofilm formation is a widespread phenomenon observed in various bacterial species, characterized by the aggregation of cells within a self-produced extracellular matrix composed of polysaccharides, proteins, and nucleic acids. This complex structure enables bacteria to adhere to surfaces and establish stable communities, which confer numerous advantages, including enhanced resistance to environmental stressors and increased tolerance to antimicrobial agents. Biofilms are implicated in a range of critical issues across multiple domains, including medicine, industry, and environmental science. In clinical settings, biofilms are notorious for their role in chronic infections and their association with antibiotic resistance, leading to significant challenges in treatment and patient management [1][2]. Therefore, understanding the mechanisms underlying biofilm development is of paramount importance.

The significance of biofilm research extends beyond mere academic interest; it is vital for addressing pressing public health concerns. Infections caused by biofilm-forming bacteria, such as Staphylococcus aureus and Pseudomonas aeruginosa, are particularly difficult to treat due to their enhanced resistance to both the immune response and conventional antibiotics [3][4]. These infections can result in prolonged hospital stays, increased healthcare costs, and in severe cases, mortality. Additionally, biofilms are prevalent in various industrial applications, leading to equipment fouling and loss of efficiency, thereby necessitating effective management strategies [1].

Current research indicates that biofilm formation occurs in distinct stages, including initial attachment, maturation, and dispersion [5]. Initial attachment involves the adhesion of planktonic bacteria to a surface, followed by the formation of microcolonies and the production of the extracellular matrix. Maturation leads to the development of complex three-dimensional structures that facilitate nutrient exchange and communication among cells [6]. Finally, the dispersion phase allows cells to leave the biofilm and colonize new environments, thereby perpetuating the cycle of infection and resistance [7].

Recent advancements in molecular biology and bioinformatics have significantly enhanced our understanding of the genetic and environmental factors that influence biofilm development. Key regulatory genes, such as those involved in quorum sensing and cyclic di-GMP signaling, play critical roles in the transition from a planktonic to a biofilm lifestyle [8][9]. Environmental factors, including nutrient availability and surface properties, further modulate biofilm formation, highlighting the dynamic interplay between bacteria and their surroundings [10].

This review aims to provide a comprehensive overview of the current understanding of biofilm formation in bacteria. The following sections will be organized as follows: first, we will delve into the mechanisms of biofilm formation, discussing the stages of initial attachment, maturation, and dispersion. Next, we will explore the genetic regulation of biofilm development, focusing on key genes and the role of quorum sensing. We will then examine the environmental factors influencing biofilm formation, including nutrient availability and surface characteristics. The implications for infection control and treatment will be discussed, addressing the challenges posed by biofilm-associated infections and potential strategies for biofilm disruption. Finally, we will outline future directions in biofilm research, highlighting emerging technologies and therapeutic approaches that may pave the way for more effective management of biofilm-related issues.

In summary, understanding the intricacies of biofilm formation is crucial for developing targeted interventions to combat biofilm-associated infections and improve clinical outcomes. By synthesizing existing literature, this review will highlight key findings and identify gaps in knowledge that warrant further investigation, ultimately contributing to the advancement of biofilm research and its applications in medicine and beyond.

2 Mechanisms of Biofilm Formation ​

2.1 Initial Attachment ​

Bacterial biofilm formation is a complex process characterized by several distinct phases, with the initial attachment phase being crucial for the establishment of biofilms. This phase involves the adhesion of planktonic bacteria to biotic or abiotic surfaces and is influenced by various physicochemical factors, as well as biological interactions.

The initial attachment is often reversible and can be dictated by the physicochemical and electrostatic interactions between the bacterial cells and the surface they encounter. Depending on the nature of these interactions, attachment can either be transient or lead to more permanent adhesion. To achieve irreversible attachment, bacteria utilize a variety of surface adhesins, which promote specific or nonspecific adhesion under different environmental conditions. Gram-negative bacteria, for instance, employ fimbrial, nonfimbrial, and polysaccharide adhesins to facilitate this process [11].

During this initial phase, the reversible adhesion of bacteria is typically time-consuming and unstable. Studies have shown that the time required for this process can be significantly reduced by increasing the initial concentration of bacteria, primarily due to a higher deposition rate at elevated concentrations [12]. Additionally, environmental factors such as shear stress can affect the stability of this attachment, with higher shear stress leading to improved reversibility of unstable bacterial attachment [12].

The transition from reversible to irreversible attachment is a critical step that often involves the production of extracellular polymeric substances (EPS). These substances, which are primarily composed of polysaccharides, proteins, and occasionally DNA, play a significant role in strengthening the attachment of bacteria to surfaces and facilitating the formation of mature biofilms [13]. The synthesis of EPS is closely linked to the overall biofilm development cycle and is regulated by complex genetic networks and post-transcriptional mechanisms [5].

Furthermore, the initial bacterial adhesion process can be influenced by the physical and chemical properties of the surface. For example, the hydrophobicity or hydrophilicity of the surface can significantly affect bacterial attachment rates. Bacteria such as Escherichia coli and Pseudomonas aeruginosa demonstrate different attachment behaviors on hydrophilic versus hydrophobic surfaces, which can be explained by the interaction energies involved [14].

In summary, the development of bacterial biofilms begins with the initial attachment phase, which is governed by a combination of reversible adhesion, surface properties, and the production of EPS. Understanding these mechanisms is essential for controlling biofilm formation, particularly in healthcare settings where biofilms can lead to persistent infections and complications associated with medical devices [15].

2.2 Maturation of Biofilm Structure ​

Biofilm formation in bacteria is a multifaceted process characterized by several stages, leading to the development of a mature biofilm structure. Initially, planktonic bacteria attach to a surface, which marks the beginning of biofilm formation. This attachment is followed by bacterial replication and cell-to-cell adhesion, resulting in the formation of microcolonies. As these microcolonies develop, they produce an extracellular matrix composed of polysaccharides, proteins, and extracellular DNA, which is essential for the structural integrity of the biofilm [5].

The maturation of biofilm structure involves a complex interplay of genetic and environmental factors. During this phase, the biofilm develops into a three-dimensional structure characterized by increased cell density and metabolic heterogeneity. This maturation process is facilitated by the synthesis of extracellular polymeric substances (EPS), which serve to encapsulate the bacterial cells and provide protection against environmental stresses, including antibiotic exposure [8]. The transition from the initial attachment phase to a mature biofilm is regulated by a variety of signaling molecules, including cyclic dinucleotides such as cyclic-di-GMP, which play a crucial role in the switch between motile and sessile lifestyles [5].

As the biofilm matures, it becomes more resilient, exhibiting enhanced resistance to antibiotics and immune responses. This resilience is partly due to the presence of gradients of nutrients and oxygen within the biofilm, which creates different metabolic states among the bacterial cells. Cells located deeper within the biofilm often exhibit slower metabolic rates, which contribute to their increased tolerance to antimicrobial agents [16].

Moreover, biofilms are dynamic systems that can undergo disassembly, leading to the release of planktonic cells that can spread to new environments. This dispersal mechanism is an integral part of the biofilm lifecycle and contributes to the persistence of bacterial infections, particularly in clinical settings [17].

In summary, the maturation of biofilm structure is a complex process that involves initial attachment, microcolony formation, extracellular matrix production, and the establishment of a protective environment that enhances bacterial survival and resistance. Understanding these mechanisms is critical for developing strategies to combat biofilm-associated infections and improve treatment outcomes.

2.3 Dispersion of Biofilm Cells ​

Biofilm formation by bacteria is a complex process that involves several stages and mechanisms, ultimately leading to the establishment of structured communities embedded in an extracellular matrix. Bacterial biofilms develop through a series of sequential steps characterized by the initial attachment of free-floating (planktonic) bacteria to a surface, followed by growth, maturation, and eventual dispersion of cells into the environment.

The initial phase of biofilm formation begins when planktonic bacteria adhere to a surface. This attachment is influenced by various environmental factors, including surface properties, hydrodynamic conditions, and the presence of signaling molecules such as quorum sensing signals. Once attached, bacteria undergo physiological changes that enable them to grow and multiply, forming microcolonies. This growth is accompanied by the production of an extracellular polymeric substance (EPS) matrix, which serves to protect the bacterial cells and enhance their resistance to environmental stresses, including antimicrobial agents and host immune responses[6].

As biofilms mature, they develop complex three-dimensional structures characterized by heterogeneous cell populations and varying microenvironments. This maturation phase is crucial for the biofilm's resilience and functionality, as it allows for enhanced intercellular communication and nutrient exchange among the bacteria[18]. The biofilm matrix, composed of polysaccharides, proteins, and extracellular DNA, not only provides structural integrity but also plays a role in the regulation of biofilm dynamics[18].

Dispersion of biofilm cells is a critical process that enables bacteria to colonize new environments and facilitates the spread of infections. Dispersion can occur through two primary mechanisms: stimuli-induced dispersal and disassembly due to degradation of the biofilm matrix. Environmental triggers, such as changes in nutrient availability, shear stress, or the presence of certain chemicals, can induce bacteria to exit the biofilm. For instance, in a study involving Pseudomonas aeruginosa, chemical-induced dispersal (CID) was shown to rely on specific genetic and motility factors, allowing bacteria to leave the biofilm as single cells[19].

Alternatively, enzymatic disassembly (EDA) of the biofilm matrix can lead to the release of clusters of cells, which can then migrate to new surfaces for colonization. This process is facilitated by the degradation of key components of the biofilm matrix, such as polysaccharides, which may enable the bacteria to recolonize more efficiently and establish new infections[19]. The distinction between these two dispersal mechanisms highlights the complex dynamics of biofilm behavior and the adaptive strategies employed by bacteria to survive and proliferate in diverse environments[20].

Overall, the mechanisms of biofilm formation and dispersion are intricate and involve a variety of signaling pathways, environmental cues, and structural adaptations. Understanding these processes is crucial for developing strategies to combat biofilm-associated infections, which pose significant challenges in clinical and industrial settings[1].

3 Genetic Regulation of Biofilm Development ​

3.1 Key Genes Involved in Biofilm Formation ​

Bacterial biofilm formation is a complex process regulated by various genetic and physiological factors, allowing bacteria to transition from a planktonic lifestyle to a sessile, surface-associated mode of growth. This transition is not only critical for survival in hostile environments but also plays a significant role in pathogenicity and antibiotic resistance.

Biofilms are characterized by assemblages of bacteria embedded within a matrix of extracellular polymeric substances (EPS), which are crucial for attachment and protection. The regulatory networks governing biofilm formation involve multiple signaling pathways, including quorum sensing (QS) and the action of secondary messenger molecules such as cyclic adenosine monophosphate (cAMP) and cyclic dimeric guanosine monophosphate (c-di-GMP) [8][21].

Key genes involved in biofilm formation vary among different bacterial species, but several common themes emerge across studies. For instance, in Vibrio fischeri, the biofilm formation is tightly regulated by two-component signaling (TCS) regulators that control the production of symbiosis polysaccharide (Syp-PS), a major component of the biofilm matrix [22]. The regulators BinK, SypE, and SypF have been identified as critical negative regulators of biofilm formation; disruption of these genes leads to enhanced biofilm development [22].

Additionally, studies on Aeromonas hydrophila have revealed that the transcriptional regulator UidR plays a significant role in biofilm formation. Deletion of uidR resulted in increased biofilm formation, with proteomic analyses identifying 220 differentially expressed proteins associated with this regulatory mechanism [23]. Furthermore, Bacillus methylotrophicus research highlighted the role of the GntR family regulator BmfR, which activates genes responsible for extracellular polysaccharide synthesis, thereby promoting biofilm formation [24].

In Staphylococcus aureus and Staphylococcus epidermidis, the intercellular adhesion locus, primarily regulated by the icaADBC operon, is essential for biofilm formation. The expression of this operon is influenced by several global transcriptional regulators, indicating a complex regulatory network governing biofilm development [25].

The genetic regulation of biofilm formation is also influenced by small non-coding RNAs (sRNAs), which fine-tune regulatory networks by modulating the expression of proteins that either promote or inhibit biofilm formation in response to environmental cues [26].

In summary, the genetic regulation of biofilm formation involves a multifaceted network of genes and regulatory elements that interact dynamically in response to environmental stimuli. This intricate regulatory landscape not only facilitates the initial attachment of bacteria to surfaces but also governs the structural integrity and resilience of biofilms, ultimately impacting bacterial survival and pathogenicity in various contexts. Understanding these genetic mechanisms is crucial for developing strategies to control biofilm-related infections and improve bioremediation practices.

3.2 Role of Quorum Sensing in Biofilm Regulation ​

Bacterial biofilm formation is a complex process that involves coordinated behaviors among bacterial communities, primarily regulated by a mechanism known as quorum sensing (QS). QS is a cell-to-cell communication system that enables bacteria to monitor their population density and regulate gene expression accordingly. This process is mediated by small signaling molecules called autoinducers (AIs), which play a critical role in the initiation and maturation of biofilms.

The development of biofilms begins with the initial adhesion of bacterial cells to a surface, which is influenced by various environmental factors and the presence of specific signaling molecules. Once attached, bacteria communicate through QS to coordinate the production of extracellular polymeric substances (EPS), which form the structural matrix of the biofilm. This matrix not only provides physical stability but also enhances the bacteria's resistance to antimicrobial agents and environmental stresses, contributing to their survival in hostile conditions [27].

The regulation of biofilm formation through QS involves a series of genetic and molecular mechanisms. In many bacterial species, QS pathways consist of multiple components, including the synthesis and detection of AIs, which can be species-specific or involve interspecies communication. For instance, the production of N-acyl homoserine lactones (AHLs) and autoinducer-2 (AI-2) are common signaling molecules that facilitate these interactions. The binding of AIs to specific receptors triggers changes in gene expression that lead to biofilm maturation, virulence factor production, and metabolic adaptations [28].

Moreover, the role of small regulatory RNAs (sRNAs) in QS pathways has been increasingly recognized. These sRNAs can modulate the expression of QS-related genes, thereby influencing biofilm development and dispersal. They may act by enhancing or repressing the synthesis of AIs or their receptors, thus fine-tuning the bacterial response to environmental cues [29].

The intricate relationship between QS and biofilm formation also involves feedback mechanisms where biofilm cells can release signaling molecules that further promote biofilm stability and expansion. This process is critical for the pathogenicity of many bacteria, as biofilms are often associated with chronic infections and increased resistance to antibiotics [30].

In summary, the genetic regulation of biofilm development is significantly driven by quorum sensing, which orchestrates the collective behaviors of bacterial populations. This regulation encompasses the synthesis and detection of signaling molecules, the expression of genes involved in biofilm matrix production, and the modulation of various physiological processes essential for bacterial survival and virulence. Understanding these mechanisms offers potential avenues for developing novel strategies to disrupt biofilm formation and combat antibiotic resistance [27][28][30].

4 Environmental Factors Influencing Biofilm Formation ​

4.1 Nutrient Availability ​

Biofilm formation by bacteria is a complex process influenced significantly by environmental factors, particularly nutrient availability. Nutrients play a crucial role in the development and stability of biofilms, impacting both the quantity and quality of the biofilm produced.

Studies have shown that the presence of specific nutrients can enhance biofilm formation. For instance, in a study focusing on avian pathogenic Escherichia coli (APEC), it was observed that biofilm formation was strongest in M9 medium supplemented with glucose at 37°C, indicating that glucose serves as a critical nutrient that promotes biofilm development. In contrast, the biofilm formation was inhibited under acidic conditions, suggesting that the pH level, which can affect nutrient availability, also plays a significant role in biofilm dynamics [31].

In another study on Listeria monocytogenes, it was found that the addition of sodium chloride and glucose generally increased biofilm formation across various strains. The relationship between nutrient concentration and biofilm formation was strain-dependent, indicating that different bacterial species may respond uniquely to nutrient availability [32]. This highlights the importance of specific nutrient types and concentrations in influencing biofilm development.

Furthermore, in the context of water conveyance systems, research demonstrated that increased nutrient levels promoted biofilm growth but also led to greater instability within the biofilm structure, increasing the risk of secondary contamination. Nutrient escalation beyond a certain threshold had diminishing returns on biofilm community composition, suggesting that while nutrients are necessary for biofilm formation, there is a delicate balance that must be maintained [33].

The modulation of biofilm formation by nutrient availability can also be linked to the mechanical properties of the biofilm. The composition of the extracellular matrix, which provides structural integrity to biofilms, is influenced by the nutrients available. Different nutrients can alter the physical characteristics of the biofilm, including its viscosity and elasticity, thereby affecting its overall stability and resistance to environmental challenges [34].

In summary, the development of bacterial biofilms is significantly influenced by nutrient availability. The presence of specific nutrients, such as glucose and sodium chloride, can enhance biofilm formation, while their concentrations must be carefully managed to prevent instability. The interplay between nutrient availability and other environmental factors, such as pH and temperature, further complicates the biofilm formation process, necessitating a comprehensive understanding for effective management and control of biofilm-related issues in various settings.

4.2 Surface Properties and Topography ​

Bacterial biofilm formation is a complex process influenced by various environmental factors and the physicochemical properties of surfaces. The development of biofilms begins with the initial attachment of bacterial cells to a surface, which is a critical step that can be affected by surface properties such as roughness, stiffness, and chemical composition.

  1. Environmental Factors: The conditions under which bacteria grow play a significant role in biofilm development. Factors such as temperature, pH, and nutrient availability can either promote or inhibit biofilm formation. For instance, a study indicated that neutral pH and temperatures around 37°C are conducive to biofilm formation in Listeria monocytogenes, while varying concentrations of glucose and sodium chloride have strain-dependent effects on biofilm production[32]. Similarly, Stenotrophomonas maltophilia clinical isolates produced more biofilm at 32°C compared to other temperatures, highlighting the importance of environmental conditions[35].

  2. Surface Properties: The physicochemical characteristics of the surface to which bacteria attach significantly influence biofilm formation. Surface properties such as hydrophobicity, roughness, and chemical composition can dictate the extent of bacterial adhesion. For example, the study on polydimethylsiloxane surfaces demonstrated that topographical patterns, rather than the stiffness of the material, had a more pronounced effect on Escherichia coli adhesion and biofilm formation[36]. Moreover, the study found that the topography at the micron and submicron scales could impart unique properties to the surface, which are crucial for controlling bacterial behavior[36].

  3. Topography and Bacterial Adhesion: The arrangement and structure of surface features also play a critical role in bacterial attachment. Research has shown that specific topographical patterns can either enhance or reduce bacterial adhesion and biofilm formation. For instance, spatially organized microtopographic surface patterns have been found to significantly reduce bacterial adhesion and biofilm formation by 40-95% depending on the surface characteristics[37]. The geometry of these features influences how bacteria contact and settle on surfaces, with bacteria often preferring to adhere to corners and edges of textured surfaces[37].

  4. Cell Properties and Interaction: The inherent properties of bacterial cells, such as motility and surface hydrophobicity, also affect biofilm formation. Bacteria with higher motility and hydrophobic surface characteristics tend to form biofilms more effectively. For instance, the expression of motility-related genes was found to be higher in biofilm cells compared to planktonic cells, indicating a link between motility and biofilm development[32].

  5. Chemical Communication and Biofilm Organization: Bacteria also engage in chemical communication, which influences biofilm organization and community dynamics. Quorum sensing signals can modulate the growth and organization of bacterial communities, affecting the overall structure and functionality of the biofilm[38].

In summary, bacterial biofilm formation is a multifaceted process influenced by a combination of environmental factors, surface properties, and the physical and chemical characteristics of the bacteria themselves. Understanding these interactions is essential for developing strategies to control biofilm formation in various settings, particularly in clinical and industrial contexts.

4.3 Physical and Chemical Stressors ​

Bacterial biofilm formation is a complex process influenced by a variety of environmental factors, including physical and chemical stressors. The development of biofilms involves a series of stages where bacteria transition from a planktonic (free-floating) state to a sessile (attached) state, ultimately forming structured communities embedded in an extracellular polymeric substance (EPS) matrix.

The physical properties of surfaces play a critical role in the initial attachment of bacterial cells. Factors such as surface roughness, hydrophobicity, and charge can significantly affect how bacteria adhere to surfaces. For instance, Renner and Weibel (2011) emphasize that "physical properties of surfaces regulate cell attachment and physiology and affect early stages of biofilm formation" [38]. Once attached, the bacteria begin to proliferate and produce EPS, which not only aids in adhesion but also provides protection against environmental stressors.

Chemical properties, including the presence of nutrients and signaling molecules, also influence biofilm development. Silvestre et al. (2020) conducted a study on Streptococcus agalactiae and found that optimal biofilm assembly conditions were reached at pH 7.6 in the presence of glucose and inactivated human plasma, highlighting how specific chemical environments can enhance biofilm formation [39]. Furthermore, the study indicated that the composition of the extracellular matrix was primarily protein-based, suggesting that nutrient availability is crucial for the synthesis of biofilm components.

Environmental stressors such as temperature, pH, and nutrient availability can further modulate biofilm formation. For example, Silva et al. (2022) demonstrated that various environmental factors significantly influenced biofilm production in Staphylococcus species, with higher biomass observed at specific concentrations of sodium chloride and glucose, and under optimal temperature conditions [40]. Similarly, Hu et al. (2022) reported that avian pathogenic Escherichia coli exhibited the strongest biofilm formation at 25°C in Luria-Bertani medium, and the presence of glucose at 37°C enhanced biofilm development [31].

Mechanical stressors, such as hydrodynamic forces, also play a vital role in biofilm formation. Research by Jara et al. (2020) showed that hydrodynamic stress could lead to an increase in both cell density and matrix production in Pseudomonas fluorescens biofilms, suggesting that physical forces can stimulate biofilm development by enhancing nutrient diffusion and promoting the incorporation of planktonic bacteria into established biofilms [41].

Moreover, the interaction between different bacterial species within biofilms can influence their development. Madsen et al. (2016) found that social interactions among co-cultured bacteria led to increased biofilm formation, particularly among species that had coexisted in their natural environments, indicating that ecological factors also play a significant role in shaping biofilm communities [42].

In summary, bacterial biofilm formation is a multifaceted process regulated by an interplay of physical and chemical environmental factors, including surface properties, nutrient availability, and mechanical stresses. Understanding these factors is essential for developing strategies to control biofilm formation in various settings, including medical and industrial environments.

5 Implications for Infection Control and Treatment ​

5.1 Challenges in Treating Biofilm-Associated Infections ​

Bacterial biofilm formation is a multifaceted process that involves several stages, ultimately leading to the establishment of complex microbial communities encased in an extracellular polymeric matrix. This process is characterized by the adherence of bacteria to surfaces, where they aggregate and proliferate to form microcolonies. The biofilm matrix, composed of polysaccharides, proteins, and extracellular DNA, serves as a protective barrier, significantly enhancing the bacteria's resistance to antibiotics and the host immune system, thus complicating infection control and treatment strategies.

The development of biofilms typically progresses through several key stages: initial attachment to a surface, microcolony formation, maturation of the biofilm, and eventual dispersal of cells. During the initial attachment phase, bacteria utilize various adhesion mechanisms to adhere to surfaces, which can be biotic or abiotic. Once attached, they multiply and begin to produce the extracellular matrix, which is essential for the structural integrity and function of the biofilm. As the biofilm matures, it develops into a three-dimensional structure that can exhibit complex signaling networks and chemical gradients, further enhancing its resilience against antimicrobial agents [2][43][44].

The implications of biofilm formation for infection control are profound. Biofilms are implicated in a wide range of infections, including device-related infections, chronic wounds, and persistent infections in various body sites such as the respiratory tract, urinary tract, and cardiovascular system [2]. The protective nature of biofilms allows bacteria to evade the immune response and persist in hostile environments, making infections difficult to eradicate. The presence of biofilms is associated with increased morbidity and mortality, necessitating innovative treatment approaches that go beyond conventional antibiotic therapies [4][44].

Challenges in treating biofilm-associated infections stem primarily from the inherent resistance exhibited by biofilm-embedded bacteria. These bacteria are often significantly more tolerant to antibiotics compared to their planktonic counterparts, which complicates standard treatment regimens [45]. The development of antibiotic resistance within biofilms can occur through various mechanisms, including the presence of persister cells that are inherently tolerant to antibiotics, and the ability of biofilm bacteria to acquire and disseminate resistance genes [46][47].

To effectively combat biofilm-associated infections, a multifaceted approach is required. This includes the development of novel therapeutics that target different stages of biofilm formation, such as anti-quorum sensing agents, biofilm dispersal agents, and alternative treatment modalities like CRISPR/Cas9 gene editing technology [4][45]. Additionally, strategies that modify the surfaces of medical devices to prevent biofilm adhesion, such as antibacterial coatings and surface modifications, are also critical in preventing biofilm-related infections [45][48].

In conclusion, the intricate process of biofilm formation poses significant challenges for infection control and treatment. Understanding the mechanisms underlying biofilm development and the factors contributing to their resistance is essential for developing effective strategies to prevent and treat biofilm-associated infections. Ongoing research is crucial to unravel the complexities of biofilms and to enhance therapeutic options for affected patients [2][44].

5.2 Strategies for Biofilm Disruption ​

Bacterial biofilm formation is a complex process that plays a significant role in the persistence and pathogenicity of bacterial infections. The development of biofilms involves multiple stages, characterized by the adherence of bacterial cells to surfaces, aggregation, and the production of an extracellular polymeric substance (EPS) that encapsulates the cells. This protective matrix enhances bacterial survival against antibiotics and the host immune system, thereby facilitating chronic infections.

The biofilm formation process typically begins with the initial attachment of planktonic bacteria to a surface, which can be biological (e.g., tissue) or abiotic (e.g., medical devices). Following this initial adhesion, bacteria multiply and form microcolonies, leading to the production of the EPS, which consists of polysaccharides, proteins, and extracellular DNA (eDNA) [2]. This matrix not only protects the bacteria from external threats but also creates a microenvironment that fosters bacterial growth and resilience [44].

The implications of biofilm formation for infection control are profound. Biofilms are notoriously difficult to treat due to their inherent resistance to conventional antibiotics. Bacterial cells within biofilms exhibit altered phenotypes, making them significantly more tolerant to antimicrobial agents and immune responses [4]. This resistance can lead to persistent infections that are challenging to eradicate, especially in clinical settings where medical devices are involved [45]. As such, biofilm-associated infections represent a critical concern in public health and require innovative strategies for effective management [49].

Strategies for disrupting biofilms and combating biofilm-associated infections are diverse and evolving. Current approaches can be categorized into several key strategies:

  1. Targeting Biofilm Formation: This involves disrupting the initial adhesion of bacteria to surfaces or interfering with the signaling pathways that promote biofilm development. Techniques such as using agents that inhibit quorum sensing or disrupt the production of EPS components are under investigation [50].

  2. Physical Disruption: Methods such as ultrasound, light, or magnetic fields can be employed to disrupt the biofilm matrix, making the bacteria more susceptible to antibiotics [50]. This physical approach aims to dismantle the biofilm structure, thereby releasing embedded bacterial cells and enhancing their exposure to antimicrobial agents [51].

  3. Enzymatic Treatment: Utilizing enzymes such as DNases, proteases, and polysaccharide hydrolases can degrade the EPS, which is crucial for maintaining biofilm integrity. This enzymatic approach targets the structural components of biofilms, promoting their disassembly [52].

  4. Nanotechnology: The development of nanomaterials has opened new avenues for biofilm disruption. Nanoparticles can be designed to penetrate biofilms and deliver therapeutic agents more effectively, or they can function to disrupt biofilm architecture [53].

  5. Combination Therapies: Combining traditional antibiotics with anti-biofilm agents or using multiple strategies in tandem is gaining traction. Such multi-faceted approaches aim to overcome the challenges posed by biofilm-associated infections by targeting different aspects of biofilm physiology [43].

  6. CRISPR/Cas9 Technologies: Emerging research indicates that CRISPR/Cas9 gene editing may provide novel avenues for combating biofilm-associated infections by targeting specific genes responsible for biofilm formation and antibiotic resistance [4].

In summary, the formation of bacterial biofilms is a sophisticated process that enhances bacterial survival and complicates infection treatment. Effective strategies for biofilm disruption are essential for improving clinical outcomes and controlling biofilm-associated infections. Ongoing research and innovation in this field hold promise for developing more effective therapeutic interventions against these resilient microbial communities.

6 Future Directions in Biofilm Research ​

6.1 Emerging Technologies for Biofilm Study ​

Bacteria develop biofilm formation through a complex and multifaceted process that involves several stages and regulatory mechanisms. Initially, bacterial cells adhere to a surface, which is a critical first step in biofilm development. This adhesion is influenced by various physico-chemical factors, including surface properties and environmental conditions. Once attached, bacteria proliferate and form microcolonies, which further develop into a mature biofilm embedded in an extracellular polymeric substance (EPS) matrix composed of polysaccharides, proteins, and extracellular DNA [1][5].

The transition from initial attachment to mature biofilm formation is regulated by intricate signaling networks, including quorum sensing (QS) and the involvement of secondary messenger molecules such as cyclic dimeric guanosine monophosphate (c-di-GMP) [8]. These regulatory systems allow bacteria to communicate and coordinate their behavior in response to environmental cues, promoting the formation of biofilms as a survival strategy, especially in hostile conditions [1].

Emerging technologies are playing a crucial role in advancing our understanding of biofilm formation. Microfluidic approaches, for instance, enable researchers to manipulate hydrodynamic conditions and chemical gradients in real-time, allowing for high-throughput studies of biofilm development [54]. This technology can help elucidate the effects of various environmental factors on biofilm dynamics and gene expression.

Moreover, the use of advanced imaging techniques and transcriptomics has provided insights into the spatial organization and metabolic activity within biofilms, revealing the heterogeneity of bacterial communities and their responses to treatments [55]. These innovations are vital for developing new therapeutic strategies to combat biofilm-associated infections, which are notoriously resistant to conventional antibiotics [4].

In summary, the development of bacterial biofilms is a highly regulated process influenced by multiple environmental and cellular factors. The integration of emerging technologies into biofilm research is essential for uncovering the underlying mechanisms of biofilm formation and for devising effective strategies to prevent and control biofilm-related infections. Future research will likely focus on the application of these technologies to explore biofilm behavior in more complex environments and to identify novel targets for intervention [18].

6.2 Potential Therapeutic Approaches ​

Bacterial biofilm formation is a complex process characterized by the adherence of bacteria to surfaces and the subsequent production of an extracellular polymeric substance (EPS) that encases the cells. This process typically unfolds in several stages, which include initial attachment, microcolony formation, maturation, and dispersion. Each of these stages is regulated by various environmental factors and signaling mechanisms.

Initially, bacteria attach to a surface through weak van der Waals forces and then establish more permanent adhesion through specific interactions, often involving surface structures such as pili or fimbriae. Once attached, the bacteria begin to multiply and form microcolonies, during which they produce EPS composed of polysaccharides, proteins, and extracellular DNA (eDNA) [1]. The EPS serves multiple functions, including providing structural integrity, protecting against environmental stresses, and facilitating nutrient acquisition [4].

As biofilms mature, they develop into complex three-dimensional structures, which enhance their resilience against antimicrobial agents and host immune responses [47]. This structural complexity is a key factor in the persistence of biofilm-associated infections, as the biofilm matrix can significantly reduce the penetration of antibiotics, leading to treatment failures [49].

Future directions in biofilm research focus on understanding the intricate signaling networks that govern biofilm development, including quorum sensing and other regulatory pathways. Advances in bioinformatics, transcriptomics, and proteomics are expected to provide deeper insights into the molecular mechanisms of biofilm formation and maintenance [4]. These technologies can help identify novel therapeutic targets, as well as small molecules that could disrupt biofilm formation or enhance the efficacy of existing antibiotics [56].

Potential therapeutic approaches to combat biofilm-related infections are increasingly diverse and innovative. Strategies include the development of biofilm inhibitors that target specific stages of biofilm formation, such as disrupting initial adhesion or interfering with the EPS matrix [52]. Additionally, the use of nanotechnology has emerged as a promising avenue, with nanoparticles being designed to enhance antibiotic delivery, disrupt biofilm structures, or modulate bacterial metabolism [57]. Other approaches include the use of phage therapy, antimicrobial peptides, and bioactive compounds derived from natural sources [58].

Overall, addressing biofilm-associated infections requires a multifaceted approach that combines understanding the fundamental biology of biofilms with innovative therapeutic strategies. The ongoing research in this field holds the potential to significantly improve treatment outcomes for infections that are currently difficult to manage due to the resilience of biofilms.

7 Conclusion ​

The formation of bacterial biofilms represents a significant challenge in both clinical and industrial contexts, due to their complex structure and inherent resistance to antimicrobial treatments. This review highlights key findings regarding the mechanisms of biofilm formation, including initial attachment, maturation, and dispersion, as well as the genetic and environmental factors that influence these processes. Key regulatory genes and quorum sensing pathways have been identified as critical components in the transition from planktonic to biofilm lifestyles, emphasizing the need for further research in this area. Current treatment strategies for biofilm-associated infections face significant obstacles due to the protective nature of biofilms, necessitating innovative approaches such as targeting biofilm formation and employing combination therapies. Future research directions should focus on the application of emerging technologies to better understand biofilm dynamics and the development of novel therapeutic strategies aimed at disrupting biofilm integrity and enhancing treatment efficacy. The insights gained from this review can guide future investigations into biofilm management, ultimately contributing to improved patient outcomes and reduced economic burdens associated with biofilm-related infections.

References ​

  • [1] Xinyu Wang;Ming Liu;Chuanjiang Yu;Jing Li;Xikun Zhou. Biofilm formation: mechanistic insights and therapeutic targets.. Molecular biomedicine(IF=10.1). 2023. PMID:38097907. DOI: 10.1186/s43556-023-00164-w.
  • [2] Damini Thakur;Lokender Kumar. Biofilm-associated Escherichia coli infections: pathogenesis, clinical implications, and treatment strategies.. Critical reviews in microbiology(IF=5.1). 2025. PMID:40832759. DOI: 10.1080/1040841X.2025.2548490.
  • [3] Qi Peng;Xiaohua Tang;Wanyang Dong;Ning Sun;Wenchang Yuan. A Review of Biofilm Formation of Staphylococcus aureus and Its Regulation Mechanism.. Antibiotics (Basel, Switzerland)(IF=4.6). 2022. PMID:36671212. DOI: 10.3390/antibiotics12010012.
  • [4] Azna Zuberi;Nayeem Ahmad;Hafiz Ahmad;Mohd Saeed;Irfan Ahmad. Beyond antibiotics: CRISPR/Cas9 triumph over biofilm-associated antibiotic resistance infections.. Frontiers in cellular and infection microbiology(IF=4.8). 2024. PMID:39035353. DOI: 10.3389/fcimb.2024.1408569.
  • [5] Luary C Martínez;Viveka Vadyvaloo. Mechanisms of post-transcriptional gene regulation in bacterial biofilms.. Frontiers in cellular and infection microbiology(IF=4.8). 2014. PMID:24724055. DOI: 10.3389/fcimb.2014.00038.
  • [6] Daniel López;Hera Vlamakis;Roberto Kolter. Biofilms.. Cold Spring Harbor perspectives in biology(IF=8.4). 2010. PMID:20519345. DOI: 10.1101/cshperspect.a000398.
  • [7] Rui Guo;Xialin Luo;Jingjing Liu;Haitao Lu. Mass spectrometry based targeted metabolomics precisely characterized new functional metabolites that regulate biofilm formation in Escherichia coli.. Analytica chimica acta(IF=6.0). 2021. PMID:33453877. DOI: 10.1016/j.aca.2020.12.021.
  • [8] Kumari Uma Mahto;Swetambari Kumari;Surajit Das. Unraveling the complex regulatory networks in biofilm formation in bacteria and relevance of biofilms in environmental remediation.. Critical reviews in biochemistry and molecular biology(IF=6.4). 2022. PMID:34937434. DOI: 10.1080/10409238.2021.2015747.
  • [9] Nira Rabin;Yue Zheng;Clement Opoku-Temeng;Yixuan Du;Eric Bonsu;Herman O Sintim. Biofilm formation mechanisms and targets for developing antibiofilm agents.. Future medicinal chemistry(IF=3.4). 2015. PMID:25875875. DOI: 10.4155/fmc.15.6.
  • [10] Vera Carniello;Brandon W Peterson;Henny C van der Mei;Henk J Busscher. Physico-chemistry from initial bacterial adhesion to surface-programmed biofilm growth.. Advances in colloid and interface science(IF=19.3). 2018. PMID:30376953. DOI: 10.1016/j.cis.2018.10.005.
  • [11] Cécile Berne;Adrien Ducret;Gail G Hardy;Yves V Brun. Adhesins Involved in Attachment to Abiotic Surfaces by Gram-Negative Bacteria.. Microbiology spectrum(IF=3.8). 2015. PMID:26350310. DOI: 10.1128/microbiolspec.MB-0018-2015.
  • [12] Jinfeng Wang;Qiuju Liu;Deyuan Dong;Haidong Hu;Bing Wu;Hongqiang Ren. In-situ monitoring of the unstable bacterial adhesion process during wastewater biofilm formation: A comprehensive study.. Environment international(IF=9.7). 2020. PMID:32474216. DOI: 10.1016/j.envint.2020.105722.
  • [13] Kanchana Chathoth;Louis Fostier;Bénédicte Martin;Christine Baysse;Fabrice Mahé. A Multi-Skilled Mathematical Model of Bacterial Attachment in Initiation of Biofilms.. Microorganisms(IF=4.2). 2022. PMID:35456739. DOI: 10.3390/microorganisms10040686.
  • [14] Hua Wang;Maysam Sodagari;Yajie Chen;Xin He;Bi-min Zhang Newby;Lu-Kwang Ju. Initial bacterial attachment in slow flowing systems: effects of cell and substrate surface properties.. Colloids and surfaces. B, Biointerfaces(IF=5.6). 2011. PMID:21715146. DOI: 10.1016/j.colsurfb.2011.05.053.
  • [15] Chanchan Yu;Di Zhang;Xueyan Feng;Yahong Chai;Pan Lu;Qilong Li;Feng Feng;Xiuyu Wang;Yao Li. Nanoprobe-based force spectroscopy as a versatile platform for probing the mechanical adhesion of bacteria.. Nanoscale(IF=5.1). 2019. PMID:30720812. DOI: 10.1039/c8nr10338k.
  • [16] Niels Høiby;Thomas Bjarnsholt;Michael Givskov;Søren Molin;Oana Ciofu. Antibiotic resistance of bacterial biofilms.. International journal of antimicrobial agents(IF=4.6). 2010. PMID:20149602. DOI: 10.1016/j.ijantimicag.2009.12.011.
  • [17] Katrin Schilcher;Alexander R Horswill. Staphylococcal Biofilm Development: Structure, Regulation, and Treatment Strategies.. Microbiology and molecular biology reviews : MMBR(IF=7.8). 2020. PMID:32792334. DOI: 10.1128/MMBR.00026-19.
  • [18] Evita Balducci;Francesco Papi;Daniela Eloisa Capialbi;Linda Del Bino. Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens.. International journal of molecular sciences(IF=4.9). 2023. PMID:36835442. DOI: 10.3390/ijms24044030.
  • [19] Yeping Ma;Yanlin Deng;Haojun Hua;Bee Luan Khoo;Song Lin Chua. Distinct bacterial population dynamics and disease dissemination after biofilm dispersal and disassembly.. The ISME journal(IF=10.0). 2023. PMID:37270584. DOI: 10.1038/s41396-023-01446-5.
  • [20] Qiuhong Zhang;Zhen Luo;Weiyao Han;Lu Peng;Hao Tang;Jiajia Xu;Yufan Sun;Rui Zhou;Lu Li. Ammonia-induced dispersion and proliferation of Actinobacillus pleuropneumoniae biofilms.. Microbial pathogenesis(IF=3.5). 2025. PMID:40885293. DOI: 10.1016/j.micpath.2025.108010.
  • [21] Nefise Akçelik;Mustafa Akçelik. What makes another life possible in bacteria? Global regulators as architects of bacterial biofilms.. World journal of microbiology & biotechnology(IF=4.2). 2022. PMID:36229744. DOI: 10.1007/s11274-022-03376-4.
  • [22] Cecilia M Thompson;Anne E Marsden;Alice H Tischler;Jovanka Koo;Karen L Visick. Vibrio fischeri Biofilm Formation Prevented by a Trio of Regulators.. Applied and environmental microbiology(IF=3.7). 2018. PMID:30030225. DOI: 10.1128/AEM.01257-18.
  • [23] Xiaoyan Li;Feng Tian;Binghui Zhang;Lishan Zhang;Xiaomeng Chen;Xiaoke Lin;Yuqian Wang;Xiangmin Lin;Yanling Liu. Quantitative proteomics analysis reveals an important role of the transcriptional regulator UidR in the bacterial biofilm formation of Aeromonas hydrophila.. Frontiers in cellular and infection microbiology(IF=4.8). 2024. PMID:38585655. DOI: 10.3389/fcimb.2024.1380747.
  • [24] Shanshan Xu;Zengzhi Liu;Pengfei Ren;Yang Liu;Fei Xiao;Wenli Li. BmfR, a novel GntR family regulator, regulates biofilm formation in marine-derived, Bacillus methylotrophicus B-9987.. Microbiological research(IF=6.9). 2024. PMID:39098095. DOI: 10.1016/j.micres.2024.127859.
  • [25] David Cue;Mei G Lei;Chia Y Lee. Genetic regulation of the intercellular adhesion locus in staphylococci.. Frontiers in cellular and infection microbiology(IF=4.8). 2012. PMID:23061050. DOI: 10.3389/fcimb.2012.00038.
  • [26] Jacob R Chambers;Karin Sauer. Small RNAs and their role in biofilm formation.. Trends in microbiology(IF=14.9). 2013. PMID:23178000. DOI: .
  • [27] Edyta Juszczuk-Kubiak. Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination.. International journal of molecular sciences(IF=4.9). 2024. PMID:38473900. DOI: 10.3390/ijms25052655.
  • [28] Yingsong Wang;Zeran Bian;Yan Wang. Biofilm formation and inhibition mediated by bacterial quorum sensing.. Applied microbiology and biotechnology(IF=4.3). 2022. PMID:36089638. DOI: 10.1007/s00253-022-12150-3.
  • [29] Sine Lo Svenningsen. Small RNA-Based Regulation of Bacterial Quorum Sensing and Biofilm Formation.. Microbiology spectrum(IF=3.8). 2018. PMID:30003870. DOI: 10.1128/microbiolspec.RWR-0017-2018.
  • [30] Kinga Markowska;Ksenia Szymanek-Majchrzak;Hanna Pituch;Anna Majewska. Understanding Quorum-Sensing and Biofilm Forming in Anaerobic Bacterial Communities.. International journal of molecular sciences(IF=4.9). 2024. PMID:39684519. DOI: 10.3390/ijms252312808.
  • [31] Jiangang Hu;Xiaolong Lv;Xiangpeng Niu;Fangheng Yu;Jiakun Zuo;Yinli Bao;Huifang Yin;Cuiqin Huang;Saqib Nawaz;Wen Zhou;Wei Jiang;Zhaoguo Chen;Jian Tu;Kezong Qi;Xiangan Han. Effect of nutritional and environmental conditions on biofilm formation of avian pathogenic Escherichia coli.. Journal of applied microbiology(IF=3.2). 2022. PMID:35343028. DOI: 10.1111/jam.15543.
  • [32] Yun Fan;Jiaju Qiao;Zhaoxin Lu;Zhiyang Fen;Yang Tao;Fengxia Lv;Haizhen Zhao;Chong Zhang;Xiaomei Bie. Influence of different factors on biofilm formation of Listeria monocytogenes and the regulation of cheY gene.. Food research international (Ottawa, Ont.)(IF=8.0). 2020. PMID:33233092. DOI: 10.1016/j.foodres.2020.109405.
  • [33] Yifan Hu;Ruiting Li;Kaiqin Bian;Qing Zhou;Yang Pan;Lin Ye;Aimin Li;Peng Shi. Biofilm formation dynamics in long-distance water conveyance pipelines: Impacts of nutrient levels and metal stress.. Water research(IF=12.4). 2025. PMID:39461210. DOI: 10.1016/j.watres.2024.122672.
  • [34] Marwa Tallawi;Madeleine Opitz;Oliver Lieleg. Modulation of the mechanical properties of bacterial biofilms in response to environmental challenges.. Biomaterials science(IF=5.7). 2017. PMID:28276541. DOI: 10.1039/c6bm00832a.
  • [35] G Di Bonaventura;S Stepanović;C Picciani;A Pompilio;R Piccolomini. Effect of environmental factors on biofilm formation by clinical Stenotrophomonas maltophilia isolates.. Folia microbiologica(IF=3.1). 2007. PMID:17571802. DOI: 10.1007/BF02932144.
  • [36] Sandra L Arias;Joshua Devorkin;Ana Civantos;Jean Paul Allain. Escherichia coli Adhesion and Biofilm Formation on Polydimethylsiloxane are Independent of Substrate Stiffness.. Langmuir : the ACS journal of surfaces and colloids(IF=3.9). 2021. PMID:32255642. DOI: 10.1021/acs.langmuir.0c00130.
  • [37] Virginia Vadillo-Rodríguez;Ana Isabel Guerra-García-Mora;David Perera-Costa;María Luisa Gónzalez-Martín;María Coronada Fernández-Calderón. Bacterial response to spatially organized microtopographic surface patterns with nanometer scale roughness.. Colloids and surfaces. B, Biointerfaces(IF=5.6). 2018. PMID:29800909. DOI: 10.1016/j.colsurfb.2018.05.038.
  • [38] Lars D Renner;Douglas B Weibel. Physicochemical regulation of biofilm formation.. MRS bulletin(IF=4.9). 2011. PMID:22125358. DOI: 10.1557/mrs.2011.65.
  • [39] Inês Silvestre;Maria José Borrego;Luísa Jordão. Biofilm formation by ST17 and ST19 strains of Streptococcus agalactiae.. Research in microbiology(IF=3.4). 2020. PMID:32896574. DOI: 10.1016/j.resmic.2020.08.001.
  • [40] Vanessa Silva;José Eduardo Pereira;Luís Maltez;Patrícia Poeta;Gilberto Igrejas. Influence of Environmental Factors on Biofilm Formation of Staphylococci Isolated from Wastewater and Surface Water.. Pathogens (Basel, Switzerland)(IF=3.3). 2022. PMID:36297126. DOI: 10.3390/pathogens11101069.
  • [41] Josué Jara;Francisco Alarcón;Ajay K Monnappa;José Ignacio Santos;Valentino Bianco;Pin Nie;Massimo Pica Ciamarra;Ángeles Canales;Luis Dinis;Iván López-Montero;Chantal Valeriani;Belén Orgaz. Self-Adaptation of Pseudomonas fluorescens Biofilms to Hydrodynamic Stress.. Frontiers in microbiology(IF=4.5). 2020. PMID:33510716. DOI: 10.3389/fmicb.2020.588884.
  • [42] Jonas S Madsen;Henriette L Røder;Jakob Russel;Helle Sørensen;Mette Burmølle;Søren J Sørensen. Coexistence facilitates interspecific biofilm formation in complex microbial communities.. Environmental microbiology(IF=4.0). 2016. PMID:27119650. DOI: 10.1111/1462-2920.13335.
  • [43] Ronni A G da Silva;Irina Afonina;Kimberly A Kline. Eradicating biofilm infections: an update on current and prospective approaches.. Current opinion in microbiology(IF=7.5). 2021. PMID:34333239. DOI: 10.1016/j.mib.2021.07.001.
  • [44] Ailing Zhao;Jiazheng Sun;Yipin Liu. Understanding bacterial biofilms: From definition to treatment strategies.. Frontiers in cellular and infection microbiology(IF=4.8). 2023. PMID:37091673. DOI: 10.3389/fcimb.2023.1137947.
  • [45] Panxin Li;Rui Yin;Juanli Cheng;Jinshui Lin. Bacterial Biofilm Formation on Biomaterials and Approaches to Its Treatment and Prevention.. International journal of molecular sciences(IF=4.9). 2023. PMID:37511440. DOI: 10.3390/ijms241411680.
  • [46] Jose Luis Del Pozo. Biofilm-related disease.. Expert review of anti-infective therapy(IF=3.8). 2018. PMID:29235402. DOI: 10.1080/14787210.2018.1417036.
  • [47] Ramanathan Srinivasan;Sivasubramanian Santhakumari;Pandurangan Poonguzhali;Mani Geetha;Madhu Dyavaiah;Lin Xiangmin. Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections.. Frontiers in microbiology(IF=4.5). 2021. PMID:34054785. DOI: 10.3389/fmicb.2021.676458.
  • [48] Zohra Khatoon;Christopher D McTiernan;Erik J Suuronen;Thien-Fah Mah;Emilio I Alarcon. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention.. Heliyon(IF=3.6). 2018. PMID:30619958. DOI: 10.1016/j.heliyon.2018.e01067.
  • [49] Sadeeq Ullah;Yong Chen;Chunyan Wu;Yasir Abbas;Yangqing Zhong;Xiaohui Chen;Junyin Tan;Hefa Cheng;Lu Li. Mechanistic insights and therapeutic innovations in engineered nanomaterial-driven disruption of biofilm dynamics.. RSC advances(IF=4.6). 2025. PMID:40626069. DOI: 10.1039/d5ra01711d.
  • [50] Yaping Liu;Ran Chen;Shangpeng Liu;Jing Chen;Min Sun;Zhen Fan;Jianzhong Du. Eradicating Biofilms: Decoding Persistent Mechanisms and Combating Therapeutic Strategies.. Advanced healthcare materials(IF=9.6). 2025. PMID:41178163. DOI: 10.1002/adhm.202502707.
  • [51] Miao Yu;Song Lin Chua. Demolishing the great wall of biofilms in Gram-negative bacteria: To disrupt or disperse?. Medicinal research reviews(IF=11.6). 2020. PMID:31746489. DOI: 10.1002/med.21647.
  • [52] Ruixiang Ma;Xianli Hu;Xianzuo Zhang;Wenzhi Wang;Jiaxuan Sun;Zheng Su;Chen Zhu. Strategies to prevent, curb and eliminate biofilm formation based on the characteristics of various periods in one biofilm life cycle.. Frontiers in cellular and infection microbiology(IF=4.8). 2022. PMID:36211965. DOI: 10.3389/fcimb.2022.1003033.
  • [53] Jiahe Wu;Bo Zhang;Nengming Lin;Jianqing Gao. Recent nanotechnology-based strategies for interfering with the life cycle of bacterial biofilms.. Biomaterials science(IF=5.7). 2023. PMID:36723075. DOI: 10.1039/d2bm01783k.
  • [54] Junghyun Kim;Hee-Deung Park;Seok Chung. Microfluidic approaches to bacterial biofilm formation.. Molecules (Basel, Switzerland)(IF=4.6). 2012. PMID:22895027. DOI: 10.3390/molecules17089818.
  • [55] Alejandra L Ibáñez de Aldecoa;Olga Zafra;José E González-Pastor. Mechanisms and Regulation of Extracellular DNA Release and Its Biological Roles in Microbial Communities.. Frontiers in microbiology(IF=4.5). 2017. PMID:28798731. DOI: 10.3389/fmicb.2017.01390.
  • [56] Yogesh Dutt;Ruby Dhiman;Tanya Singh;Arpana Vibhuti;Archana Gupta;Ramendra Pati Pandey;V Samuel Raj;Chung-Ming Chang;Anjali Priyadarshini. The Association between Biofilm Formation and Antimicrobial Resistance with Possible Ingenious Bio-Remedial Approaches.. Antibiotics (Basel, Switzerland)(IF=4.6). 2022. PMID:35884186. DOI: 10.3390/antibiotics11070930.
  • [57] Beiliang Miao;Dianhong Wang;Li Yu;Xiangfei Meng;Shiyi Liu;Mengqi Gao;Jiatong Han;Zeliang Chen;Ping Li;Shiwei Liu. Mechanism and nanotechnological-based therapeutics for tolerance and resistance of bacterial biofilms.. Microbiological research(IF=6.9). 2025. PMID:39642765. DOI: 10.1016/j.micres.2024.127987.
  • [58] Meng Chen;Qingsong Yu;Hongmin Sun. Novel strategies for the prevention and treatment of biofilm related infections.. International journal of molecular sciences(IF=4.9). 2013. PMID:24018891. DOI: 10.3390/ijms140918488.

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