Glutathione Reductase Encoding Gene (gor) is Associated with Oxidative Stress and Antibiotic Susceptibility in Pseudomonas aeruginosa
Annual Research & Review in Biology,
Pseudomonas aeruginosa is a major causative agent of the hospital- and community-acquired infections. These infections are often antibiotic resistant and difficult to treat. Several intrinsic and acquired resistance mechanisms to antibiotics have reported in P. aeruginosa. Recently, oxidative- stress-scavenging-systems have suggested as a possible intrinsic resistance mechanism to antibiotics because oxidative stresses induced by bactericidal antibiotics contribute to bacterial killing effects. However, this remains controversial such that further clarification is required. Glutathione reductase is a key enzyme in the maintenance of the optimum level of intracellular glutathione-redox potential to ensure normal functioning of cellular processes including the detoxification of oxidative stress. In this study, the role of a glutathione-reductase-encoding gene (gor) in oxidative stress and antibiotic susceptibility was determined in P. aeruginosa. Results showed that a gor-mutant strain was more susceptible to hydrogen peroxide (but not superoxide) than the parental strain and 100% of cells were killed with 0.01% hydrogen peroxide while the parental strain survived at the same concentration of hydrogen peroxide. The gor-mutant strain was also more susceptible to carbenicillin, chloramphenicol, ciprofloxacin, and tetracycline than the parental strain, which was confirmed by bacterial killing-kinetics. These results suggest that the gor gene is associated with oxidative stress and susceptibility to bactericidal as well as bacteriostatic antibiotics and that the oxidative-stress-scavenging-systems may be a possible drug-target for multidrug resistant P. aeruginosa.
- Glutathione reductase
- oxidative stress
- antibiotic susceptibility
- Pseudomonas aeruginosa
How to Cite
Matta R, Hallit S, Hallit R, Bawab W, Rogues AM, Salameh P. Epidemiology and microbiological profile comparison between community and hospital acquired infections: A multicenter retrospective study in Lebanon. Journal of Infection and Public Health. 2018;11:405-411.
Zavascki AP, Carvalhaes CG, Picao RC, Gales AC. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy. Expert Review of Anti-infective Therapy. 2010;8:71-93.
Cerceo E, Deitelzweig SB, Sherman BM, Amin AN. Multidrug-resistant gram-negative bacterial infections in the hospital setting: Overview, implications for clinical practice, and emerging treatment options. Microb Drug Resist. 2016;22:412-431.
Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv. 2019;37:177-192.
Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007;130:797-810.
Albesa I, Becerra MC, Battan PC, Paez PL. Oxidative stress involved in the antibacterial action of different antibiotics. Biochemical and Biophysical Research Communications. 2004;317:605- 609.
Van Acker H, Coenye T. The Role of Reactive Oxygen Species in Antibiotic-Mediated Killing of Bacteria. Trends in Microbiology. 2017;25:456-466.
Green J, Paget MS. Bacterial redox sensors. Nature reviews Microbiology. 2004;2:954-966.
Smirnova GV, Oktyabrsky ON. Glutathione in bacteria. Biochemistry Biokhimiia. 2005;70:1199-1211.
Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biology & Medicine. 2016;95:27-42.
Jiang F, Hellman U, Sroga GE, Bergman B, Mannervik B. Cloning, sequencing, and regulation of the glutathione reductase gene from the cyanobacterium Anabaena PCC 7120. The Journal of Biological Chemistry. 1995;270:22882-22889.
Perr ACF, Bhriain NN, Brown NL, Rouch DA. Molecular characterization of the gor gene encoding glutathione reductase from Pseudomonas aeruginosa: determinants of substrate specificity among pyridine nucleotide-disulphide oxidoreductases. Molecular Microbiology. 1991;5:163-171.
Kwon DH, Lu CD. Polyamines induce resistance to cationic peptide, aminoglycoside, and quinolone antibiotics in Pseudomonas aeruginosa PAO1. Antimicrobial Agents and Chemotherapy. 2006;50:1615-1622.
Kwon DH, Hekmaty S, Seecoomar G. Homeostasis of glutathione is associated with polyamine-mediated beta-lactam susceptibility in Acinetobacter baumannii ATCC 19606. Antimicrob Agents Chemother. 2013;57:5457-5461.
Kanagaratnam R, Sheikh R, Alharbi F, Kwon DH. An efflux pump (MexAB-OprM) of Pseudomonas aeruginosa is associated with antibacterial activity of Epigallocatechin-3-gallate (EGCG). Phytomedicine. 2017;36:194-200.
Falagas ME, Rafailidis PI, Matthaiou DK, Virtzili S, Nikita D, Michalopoulos A. Pandrug- resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients. International Journal of Antimicrobial Agents. 2008;32:450- 454.
Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radic Biol Med. 2014;66:75-87.
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