Biofilm Dynamics and Therapeutic Interventions: Recent Advances and Future Directions (2020-2024)

Introduction

Bacterial biofilms, structured communities of microorganisms encased in a self-produced matrix, pose significant challenges in various fields, including medicine, food safety, and environmental science. Their inherent resistance to antimicrobial agents and host immune responses necessitates continuous research into understanding their formation, composition, and mechanisms of persistence, as well as developing novel therapeutic strategies. This mini-review summarizes recent advancements in biofilm research over the past five years, focusing on biofilm formation and matrix composition, biofilm-associated infections and resistance, and emerging therapeutic interventions.

Biofilm Formation and Matrix Composition

Understanding the initial stages of biofilm formation and the composition of the extracellular matrix is crucial for developing effective prevention and disruption strategies. Geelsu Hwang's research group has investigated the influence of surface properties, bacterial motility, and hydrodynamic conditions on bacterial surface sensing and initial adhesion, highlighting the complex interplay of factors governing early biofilm development (Sherry Li Zheng et al., 2020, Front. bioeng. biotechnol.). The importance of the biofilm matrix has been repeatedly emphasized by Stefan Wuertz's group, describing it as a multitasking shared space (Hans‐Curt Flemming et al., 2020, Nature Reviews Microbiology; Hans‐Curt Flemming et al., 2021, Nature Reviews Microbiology; Hans‐Curt Flemming et al., 2022, Nature Reviews Microbiology). Thomas Thurnheer's laboratory has focused on the biofilm matrixome, detailing the extracellular components within structured microbial communities (Lamprini Karygianni et al., 2020, Trends in Microbiology). Ákos T. Kovács's team has explored the social interactions and biofilm formation of Bacillus subtilis (Sofia Arnaouteli et al., 2020, Nature Reviews Microbiology; Sofia Arnaouteli et al., 2021, Nature Reviews Microbiology). Furthermore, Nicholas S. Jakubovics's research has specifically addressed the composition and function of the dental plaque biofilm matrix (Nicholas S. Jakubovics et al., 2021, Periodontology 2000). More recently, Kang Xiao's group has used spectroscopic fingerprints to profile the architecture of extracellular polymeric substances (EPS) in activated sludge, providing insights into the complex structure of biofilms in environmental settings (Jinlan Yu et al., 2023, Water Research). Hannah Dayton's team has shown that cellular arrangement impacts metabolic activity and antibiotic tolerance in Pseudomonas aeruginosa biofilms (Hannah Dayton et al., 2024, PLoS Biology).

Biofilm-Associated Infections and Resistance

The role of biofilms in promoting antibiotic resistance and contributing to persistent infections has been a major focus of research. Jesús Arenas's group has reviewed the mechanisms by which biofilms enhance bacterial antibiotic resistance and tolerance (Cristina Uruén et al., 2020, Antibiotics (Basel)). Several studies have focused on specific pathogens, including Acinetobacter baumannii (Alemu Gedefie et al., 2021, Infection and Drug Resistance), Pseudomonas aeruginosa (Felipe Francisco Tuon et al., 2021, Pathogens; Felipe Francisco Tuon et al., 2022, Pathogens), Staphylococcus aureus (Muhammad Mubashar Idrees et al., 2020, International Journal of Environmental Research and Public Health; Muhammad Mubashar Idrees et al., 2021, International Journal of Environmental Research and Public Health; Qi Peng et al., 2022, Antibiotics (Basel)), Klebsiella pneumoniae (Maria Eduarda Souza Guerra et al., 2022, Front. cell. infect. microbiol.; Lifeng Li et al., 2024, Front. cell. infect. microbiol.), and Candida albicans (Rafael Pereira et al., 2020, Journal of Applied Microbiology; Nicole O. Ponde et al., 2021, Critical Reviews in Microbiology; Z. Malinovská et al., 2023, J. Fungi (Basel)). Ashwani Kumar's group has investigated biofilm formation in Mycobacterium tuberculosis and its contribution to virulence and drug tolerance (Poushali Chakraborty et al., 2021, Nature Communications). Elisabeth Grohmann's team has focused on horizontal gene transfer of antibiotic resistance genes within biofilms (Claudia Michaelis et al., 2023, Antibiotics (Basel)). Mai M. Zafer's group has provided a comprehensive exploration of biofilm-mediated infections by multidrug-resistant microbes (Mai M. Zafer et al., 2024, Archives of Microbiology). Sara A. Alshaikh's research has shown the correlation between antimicrobial resistance, biofilm formation, and virulence determinants in uropathogenic Escherichia coli (Sara A. Alshaikh et al., 2024, Annals of Clinical Microbiology and Antimicrobials).

Emerging Therapeutic Interventions

The development of novel strategies to combat biofilms is a critical area of research. Vincent M. Rotello's group has reviewed the use of nanomaterial-based therapeutics for antibiotic-resistant bacterial infections (Jessa Marie Makabenta et al., 2020, Nature Reviews Microbiology). Peng Liu's and Kaiyong Cai's teams have explored near-infrared light-triggered nitric-oxide-enhanced photodynamic therapy for biofilm elimination (Yuan Zhang et al., 2020, ACS Nano). Abraham Joy's laboratory has demonstrated that peptidomimetic polyurethanes can inhibit bacterial biofilm formation and disrupt established biofilms (Apoorva Vishwakarma et al., 2021, Journal of the American Chemical Society). Lianhui Wang's group has investigated potentiating hypoxic microenvironments for antibiotic activation using photodynamic therapy (Weijun Xiu et al., 2022, Nature Communications). Yu Cai's, Heng Dong's, and Dongliang Yang's teams have explored biofilm microenvironment-responsive nanoparticles for treating bacterial infections (Yanling Hu et al., 2022, Nano Today). Shiyuan Fang's, Jiaxing Wang's, Xianlong Zhang's, and Chen Zhu's groups have developed photothermal nanozyme-based microneedle patches for refractory bacterial biofilm infections (Wanbo Zhu et al., 2022, Advanced Materials). Xiaochen Dong's laboratory has reviewed recent nanotechnologies to overcome bacterial biofilm matrix barriers (Xinyi Lv et al., 2022, Small). Wanbo Zhu's, Ming Ye's, Jiaxing Wang's, and Chen Zhu's teams have developed biofilm microenvironment-responsive self-assembly nanoreactors for biofilm-associated infections (Jiawei Mei et al., 2023, Advanced Materials). Fu‐Jian Xu's group has explored Janus nanoparticles targeting extracellular polymeric substances for biofilm elimination (Zhiwen Liu et al., 2023, Nature Communications). Huaping Li's, Fan Huang's, Xiaoli Hu's, and Yong Liu's laboratories have developed antimicrobial hybrid amphiphiles for bacterial biofilm dispersal and eradication (Yizhou Zhan et al., 2023, Advanced Functional Materials). Yang Wang's, Linqi Shi's, and Yong Liu's teams have created two-tailed dynamic covalent amphiphiles to combat bacterial biofilms (Xiaowen Hu et al., 2023, Advanced Materials). Qiuning Yu's group has focused on biofilm dispersal enzymes as a strategy to combat biofilms (Shaochi Wang et al., 2023, npj biofilms microbiomes). Ashok Kumar Yadav's laboratory has reviewed quorum sensing inhibitors as therapeutics for bacterial biofilm inhibition (Aditi Vashistha et al., 2023, Bioorganic Chemistry). Martin Pumera's team has explored chemical multiscale robotics for bacterial biofilm treatment (Carmen C. Mayorga‐Martinez et al., 2024, Chemical Society Reviews). Xianwen Wang's group has developed CuCo2O4 nanoflowers with multiple enzyme activities for treating bacterium-infected wounds via cuproptosis-like death (Wenqi Wang et al., 2024, ACS Nano). Xu Lin Chen's and Xianwen Wang's teams have created a metal natural product complex with quadruple enzymatic activity to combat infections from drug-resistant bacteria (Jie Shan et al., 2024, Acta Pharmaceutica Sinica B). Kelei Zhao's group has discovered psoralen as a quorum sensing inhibitor to suppress Pseudomonas aeruginosa virulence (Fulong Wen et al., 2024, Applied Microbiology and Biotechnology). Ronit Vogt Sionov's laboratory has shown the anti-bacterial and anti-biofilm activities of arachidonic acid against Streptococcus mutans (Manoj Chamlagain et al., 2024, Front. microbiol.). Baolin Guo's team has developed a bacteria-responsive programmed self-activating antibacterial hydrogel to remodel the regeneration microenvironment for infected wound healing (Yutong Yang et al., 2024, National Science Review). Duan Wang's group has used ultrasound-activated piezo-hot carriers to trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections (Yanli Huang et al., 2024, Nature Communications).

Conclusion

Recent advancements in biofilm research have significantly enhanced our understanding of biofilm formation, composition, and the mechanisms underlying biofilm-associated infections and resistance. Emerging therapeutic interventions, particularly those involving nanomaterials, quorum sensing inhibitors, and biofilm dispersal enzymes, hold promise for combating persistent biofilm infections. Future research should focus on translating these findings into clinically effective strategies for preventing and treating biofilm-related diseases.

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