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.
Lina Ma, Hongfei Mi, Yunxin Xue, Dai Wang, Xilin Zhao
. The mechanism of ROS regulation of antibiotic resistance and antimicrobial lethality[J]. Hereditas(Beijing), 2016
, 38(10)
: 902
-909
.
DOI: 10.16288/j.yczz.16-157
[1] Cohen ML. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science , 1992, 257(5073): 1050-1055.
[2] Livermore DM. Discovery research: the scientific challenge of finding new antibiotics. J Antimicrob Chemother , 2011, 66(9): 1941-1944.
[3] Marshall DA, McGeer A, Gough J, Grootendorst P, Buitendyk M, Simonyi S, Green K, Jaszewski B, MacLeod SM, Low DE. Impact of antibiotic administrative restrictions on trends in antibiotic resistance. Can J Public Health , 2006, 97(2): 126-131.
[4] Guo W, He Q, Wang ZY, Wei M, Yang ZW, Du Y, Wu C, He J. Influence of antimicrobial consumption on gram- negative bacteria in inpatients receiving antimicrobial resistance therapy from 2008-2013 at a tertiary hospital in Shanghai, China. Am J Infect Control , 2015, 43(4): 358-364.
[5] Bergman M, Huikko S, Pihlajamäki M, Laippala P, Palva E, Huovinen P, Seppälä H. Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997-2001. Clin Infect Dis , 2004, 38(9): 1251-1256.
[6] Bergman M, Nyberg ST, Huovinen P, Paakkari P, Hakanen AJ, the Finnish Study Group for Antimicrobial Resistance. Association between antimicrobial consumption and resistance in Escherichia coli . Antimicrob Agents Chemother , 2009, 53(3): 912-917.
[7] Malik M, Li LP, Zhao XL, Kerns RJ, Berger JM, Drlica K. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics. J Antimicrob Chemother , 2014, 69(12): 3227-3235.
[8] Long QX, Du QL, Fu TW, Drlica K, Zhao XL, Xie JP. Involvement of Holliday junction resolvase in fluoroquinolone- mediated killing of Mycobacterium smegmatis. Antimicrob Agents Chemother , 2015, 59(3): 1782-1785.
[9] Kohanski MA, DePristo MA, Collins JJ. Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol Cell , 2010, 37(3): 311-320.
[10] Alekshun MN, Levy SB. The mar regulon: multiple resistance to antibiotics and other toxic chemicals. Trends Microbiol , 1999, 7(10): 410-413.
[11] Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell , 2007, 130(5): 797-810.
[12] Rajendran M. Quinones as photosensitizer for photodynamic therapy: ROS generation, mechanism and detection methods. Photodiagnosis Photodyn Ther , 2016, 13: 175-187.
[13] Huang XW, Zhao Q, Chen DZ, Zhang LS. Mutations in the D-loop region of mitochondrial DNA and the ROS level in the tissue of Hepatocellular Carcinoma. Hereditas ( Beijing ), 2005, 27(1): 14-20. 黄学文, 赵琪, 陈道桢, 张丽珊. 肝癌组织中线粒体DNA D-Loop区碱基变异与ROS水平. 遗传, 2005, 27(1): 14-20.
[14] Sakai A, Nakanishi M, Yoshiyama K, Maki H. Impact of reactive oxygen species on spontaneous mutagenesis in Escherichia coli . Genes Cells , 2006, 11(7): 767-778.
[15] Dwyer DJ, Kohanski MA, Collins JJ. Role of reactive oxygen species in antibiotic action and resistance. Curr Opin Microbiol , 2009, 12(5): 482-489.
[16] Korshunov S, Imlay JA. Detection and quantification of superoxide formed within the periplasm of Escherichia coli . J Bacteriol , 2006, 188(17): 6326-6334.
[17] Seaver LC, Imlay JA. Are respiratory enzymes the primary sources of intracellular hydrogen peroxide? J Biol Chem , 2004, 279(47): 48742-48750.
[18] Lobritz MA, Belenky P, Porter CBM, Gutierrez A, Yang JH, Schwarz EG, Dwyer DJ, Khalil AS, Collins JJ. Antibiotic efficacy is linked to bacterial cellular respiration. Proc Natl Acad Sci USA , 2015, 112(27): 8173-8180.
[19] Goswami M, Mangoli SH, Jawali N. Involvement of reactive oxygen species in the action of ciprofloxacin against Escherichia coli . Antimicrob Agents Chemother , 2006, 50(3): 949-954.
[20] Goswami M, Mangoli SH, Jawali N. Effects of glutathione and ascorbic acid on streptomycin sensitivity of Escherichia coli . Antimicrob Agents Chemother , 2007, 51(3): 1119-1122.
[21] Seaver LC, Imlay JA. Alkyl hydroperoxide reductas
