The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

Abstract

Microbial biofilms demonstrate a decreased susceptibility to antimicrobial agents. Various mechanisms have been proposed to be involved in this recalcitrance. We focus on two of these factors. Firstly, the ability of sessile cells to actively mediate efflux of antimicrobial compounds has a profound impact on resistance and tolerance, and several studies point to the existence of biofilm-specific efflux systems. Secondly, biofilm-specific stress responses have a marked influence on cellular physiology, and contribute to the occurrence of persister cells. We provide an overview of the data that demonstrate that both processes are important for survival following exposure to antimicrobial agents.Microbial biofilms are surface-attached communities, consisting of cells embedded in an extracellular polymeric matrix that is at least partially composed of polymers produced by the microorganism themselves (1). Biofilms are omnipresent in natural and man-made environments (1, 2), and biofilm-associated bacteria are involved in a wide range of infections, including respiratory tract infections in cystic fibrosis (CF) 2 patients, chronically infected wounds, and device-related infections (3, 4). One of the hallmarks of these biofilm-associated infections is the frequent failure of antimicrobial chemotherapy. Although it is often postulated that sessile cells are more resistant to antimicrobial agents, these cells typically do not grow better than planktonic cells in the presence of antibiotics; for example, biofilm-associated and stationary-phase planktonic Burkholderia cepacia complex bacteria showed similar susceptibilities to antibiotics (5). However, it is much more difficult to kill biofilm-associated cells than planktonic cells (6), and various mechanisms that potentially could be involved in this have been described in the literature (see Refs. 7 and 8 for recent reviews as well as Refs. 9 and 10 in this minireview series). Avoiding exposure to (sufficiently high concentrations of) antibiotics, and the presence of a small population of specialized survivor cells that are tolerant toward particular antimicrobial agents (i.e. they are not killed upon exposure to the product) are two important mechanisms that will be discussed in this review.

Exogenous fatty acid metabolism in bacteria

“…Biofilms are made of primarily polysaccharides, DNA, and peptides. Biofilm formation promotes bacterial persistence and antibiotic resistance by forming dense matrices that allow the cells in the outer layer to protect the cells in the matrix [99]. Biofilm formation also promotes lateral gene transfer and cooperation between different bacterial species within the matrix [100].…”

The Effect of Quorum-Sensing and Efflux Pumps Interactions in Pseudomonas aeruginosa Against Photooxidative Stress

“…Twelve pump-encoding operons have been discovered in the genome of this bacterium. 22,23 These pumps are genetically and structurally similar; however, they are different in their substrate specificity and regulation. 24 Efflux pumps in P. aeruginosa contribute to reduced susceptibility toward most antibiotics and antibacterial agents.…”

Baicalin Inhibits Biofilm Formation and the Quorum-Sensing System by Regulating the MsrA Drug Efflux Pump in Staphylococcus saprophyticus

“…Recently, several studies have provided evidence to show that genetic inactivation and chemical inhibition of efflux pumps resulted in transcriptional inhibition of biofilm matrix components and a short biofilm formation (Baugh et al, 2014;Van Acker and Coenye, 2016;Sabatini et al, 2017). Biofilm formation is regulated by the quorum-sensing (QS) system.…”