The Three Bacterial Lines of Defense against Antimicrobial Agents

Abstract

Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their spatially distinct sites of action and distribution of location, antimicrobial resistance mechanisms of bacteria were categorized into three groups, coined the three lines of bacterial defense in this review. The first line of defense is biofilms, which can be formed by most bacteria to overcome the action of antimicrobial agents. In addition, some other bacteria employ the second line of defense, the cell wall, cell membrane, and encased efflux pumps. When antimicrobial agents permeate the first two lines of defense and finally reach the cytoplasm, many bacteria will make use of the third line of defense, including alterations of intracellular materials and gene regulation to protect themselves from harm by bactericides. The presented three lines of defense theory will help us to understand the bacterial resistance mechanisms against antimicrobial agents and design efficient strategies to overcome these resistances.

Keywords: action sites; antimicrobial agents; defense lines; new theory; resistance mechanism.

Figure 1

Simplified diagram summarizing the mechanisms of the three defense lines of resistance to antimicrobial agents for bacteria. There are three lines of defense for bacterial cells to overcome death by antimicrobial agents. The first defense line is bacterial biofilms, which limits the penetration of antimicrobial agents. The cell wall, cell membrane and the encased efflux pumps construct the second defense line to limit the absorbance or elevate the excretion of antimicrobial agents. When antimicrobial agents enter the bacterial cells, they meet the third line of defense, involving the alteration of target sites, regulation of gene expression and production of certain enzymes.