Biofilm Formation and Antibiotic Resistance in Pathogenic Bacteria: Molecular Mechanisms, Clinical Significance, and Emerging Therapeutic Strategies; A Review Article

Abstract

Bacterial biofilms are highly structured microbial communities that contain bacterial cells that bind to biotic or abiotic surfaces and are enclosed in a matrix of extracellular polymeric substance (EPS) secreted by the bacteria themselves. The ability of pathogenic bacteria to form biofilms is one of the most crucial strategies that allow these bacteria to survive and is strongly linked to persistent, recurring, and difficult-to-treat infections. The ability to resist antimicrobial agents and host immune response is significantly greater for biofilm-associated cells than for planktonic bacteria. This increased tolerance is the result of several interacting mechanisms, such as low levels of antibiotic uptake, binding to extracellular matrix, lowered metabolism, the development of persisters, activation of efflux pumps, alteration of antibiotic targets, stress response, quorum-sensing regulation and horizontal transfer of antimicrobial-resistance genes. Biofilms play a significant role in medical device-associated infections, chronic wounds, urinary catheter infections, respiratory infections, prosthetic implants and chronic lung disease. Biofilm forming organisms are important pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Enterococcus faecium and pathogenic Escherichia coli. However, recent evidence has shown that conventional genetic antibiotic resistance is not the only contributor to resistance that is biofilm associated, as there is also a significant contribution from phenotypic tolerance and physiological heterogeneity within the biofilm that is responsible for treatment failure. This is why anti-bacterial and antibiofilm approaches have become a growing part of the conventional antibiotic treatment, focusing on bacterial adhesion, quorum sensing, EPS degradation, persister cells and biofilm specific regulatory pathways. New strategies include the use of bacteriophage therapy, bacteriophage derived enzymes, anti-microbial peptides, nanoparticles, quorum-sensing inhibitors, matrix-degrading enzymes, drug delivery systems, and CRISPR based technologies. This review briefly outlines what is known about biofilm formation, mechanisms of antibiotic resistance, clinically relevant biofilm producing pathogens, and new biofilm prevention and treatment techniques. Advances in understanding the biology of biofilms could enable the development of new therapies that target bacteria and enhance treatment for chronic and multidrug-resistant bacterial infections.