The mechanism of ROS regulation of antibiotic resistance and antimicrobial lethality.
Misuse and overuse of antibiotics have led to serious resistance problems that pose a grave threat to human health. How to solve the increasing antibiotic resistance problem is a huge challenge. Besides the traditional strategy of developing novel antimicrobial agents, exploring ways to enhance the lethal activity of antibiotics currently available is another feasible approach to fight against resistance. Recent studies showed that ROS plays an important role in regulating both antibiotic resistance and antimicrobial lethality. ROS produced by sublethal levels of antibiotic induces antibiotic resistance through activating drug efflux pumps via MarR(Multiple antibiotic resistance repressor)-MarA(Multiple antibiotic resistance activator), triggers the protective function against stress via SoxR (Superoxide response transcriptional regulator)-SoxS (Superoxide response transcription factor), and promotes mutagenesis by induction of SOS system. On the contrary, ROS triggered by lethal levels of antibiotic promotes bacterial killing and suppresses resistance. In addition to the concentration of antibiotic, the role of ROS in mediating antimicrobial resistance and bacterial killing is also regulated by a series of genetic regulators (e.g. MazEF, Cpx, SoxR, MarRAB). Thus, how ROS contribute to antimicrobial resistance and bacterial killing is complex. In this review, we summarized the mechanism of ROS in regulating antibiotic resistance and antimicrobial lethality, which may provide references and guidance for finding new ways to enhance antimicrobial lethality of currently available antimicrobials and battling antibiotic resistance.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
Li-na
LN
Ma
1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China; 2. School of Public Health, Fujian Medical University, Fuzhou 350108, China.
Hong-fei
HF
Mi
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
Yun-xin
YX
Xue
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
Dai
D
Wang
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
Xi-lin
XL
Zhao
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D001424:Bacterial Infections / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017382:Reactive Oxygen Species