Mechanisms and Control Strategies of Antibiotic Resistance in Pathological Biofilms

Bacterial Biofilms Structure and Characteristics of Bacterial BiofilmThe physical scaffold of a biofilm is the matrix of extracellular polymeric substances (EPSs), self-secreted substances that keep bacterial cells in a contained structure and attach them to surfaces [8].Most of the biomass of the biofilm is hydrated EPS rather than bacterial cells, which only make up between 2% to 15% of the total biofilm mass [9].EPS is mostly composed of polysaccharides, proteins, lipids and extracellular DNA (eDNA) (Fig. 1) [9].Enhanced antimicrobial resistance, nutrient capture and social cooperation are three main characteristic features of biofilms, and the EPS matrix underlies these important properties [2].The structures of biofilms somewhat resembles tissues of higher organisms, which are structurally complex and highly heterogenous in gene expression [10], both contributing to the resistance mechanisms of biofilm. Life Cycle of Bacterial BiofilmsThe transition from planktonic growth to biofilm is a complex and highly regulated process that follows a few steps (Fig. 1).The first step is the initial attachment of planktic bacterial cells to a surface, which often happens when cells are under environmental stress.The propelling structures, such as appendages, fimbriae and sex pili, Bacterial biofilm is a community of bacteria that are embedded and structured in a self-secreted extracellular matrix.An important clinical-related characteristic of bacterial biofilms is that they are much more resistant to antimicrobial agents than the planktonic cells (up to 1,000 times), which is one of the main causes of antibiotic resistance in clinics.Therefore, infections caused by biofilms are notoriously difficult to eradicate, such as lung infection caused by Pseudomonas aeruginosa in cystic fibrosis patients.Understanding the resistance mechanisms of biofilms will provide direct insights into how we overcome such resistance.In this review, we summarize the characteristics of biofilms and chronic infections associated with bacterial biofilms.We examine the current understanding and research progress on the major mechanisms of antibiotic resistance in biofilms, including quorum sensing.We also discuss the potential strategies that may overcome biofilm-related antibiotic resistance, focusing on targeting biofilm EPSs, blocking quorum sensing signaling, and using recombinant phages.