title: 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.
authors.affiliation: Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China. zgbees@gdim.cn.|State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070, Guangdong, China. zgbees@gdim.cn.|Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou 510070, Guangdong, China. zgbees@gdim.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China. shiqingshan@hotmail.com.|State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070, Guangdong, China. shiqingshan@hotmail.com.|Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou 510070, Guangdong, China. shiqingshan@hotmail.com.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Shi
authors.affiliation: Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China. xmhuang@gdim.cn.|State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070, Guangdong, China. xmhuang@gdim.cn.|Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou 510070, Guangdong, China. xmhuang@gdim.cn.
authors.forename: Xiao-Mo
authors.initials: XM
authors.lastname: Huang
authors.affiliation: Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China. xiaobaoxie@126.com.|State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070, Guangdong, China. xiaobaoxie@126.com.|Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou 510070, Guangdong, China. xiaobaoxie@126.com.
authors.forename: Xiao-Bao
authors.initials: XB
authors.lastname: Xie
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D042541:Intracellular Space / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents
keywords: action sites; antimicrobial agents; defense lines; new theory; resistance mechanism