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http://dx.doi.org/10.15616/BSL.2021.27.2.59

Relationship between AdeABC Efflux Pump Genes and Carbapenem in Multidrug-resistant Acinetobacter baumannii  

Ju, Yeongdon (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
Kim, Yoo-Jeong (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
Chang, Chulhun L. (Department of Laboratory Medicine, Pusan National University Yangsan Hospital)
Choi, Go-Eun (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
Hyun, Kyung-Yae (Department of Clinical Laboratory Science, Dong-Eui University)
Abstract
Multidrug-resistant strain of Acinetobacter baumannii (MDRAB) is an emerging pathogen in health care facilities, preventing MDRAB is a public health concern. We conducted this experiment on a clinical isolate of A. baumannii with two main goals: the role of the efflux pump system in the stress provision of carbapenem and the response to the transcription level of the efflux pump gene. A total of 34 strains of A. baumannii was isolated from the Yangsan Hospital of Pusan National University. First, when we compared and observed the expression of the efflux pump gene and antibacterial resistance to carbapenem, a strong correlation was observed between carbapenem resistance and overexpression of adeB (P=0.0056). Second, a correlation between the efflux pump and concentration gradient and tolerance to carbapenem stress at the AdeABC efflux pump genes transcription level was confirmed. Our results revealed that the expression of the AdeABC efflux pump is an important resistance determinant in obtaining antibiotic resistance of the carbapenem group in A. baumannii.
Keywords
Acinetobacter baumannii; Carbapenem; Drug-resistance; Efflux pumps; AdeABC; adeB;
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1 Peleg AY, Adams J, Paterson DL. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2007. 51: 2065-2069.   DOI
2 Roca I, Marti S, Espinal P, Martetinez P, Gibert I, Vila J. CraA, a major facilitator superfamily efflux pump associated with chloramphenicol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother. 2009. 53: 4013-4014.   DOI
3 Shi WF, Jiang JP, Xu N, Huang ZM, Wang YY. Inhibitory effects of reserpine and carbonyl cyanide m-chloro-phenylhydrazone on fluoroquinolone resistance of Acinetobacter baumannii. Chin Med J. 2005. 118: 340-343.
4 Srinivasan VB, Rajamohan G, Gebreyes WA. The role of AbeS, a novel efflux pump member of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother. 2009. 53: 5312- 5316.   DOI
5 Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015. 13: 42-51.   DOI
6 Coyne S, Courvalin P, Perichon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother. 2011. 55.3: 947-953.   DOI
7 Bae IK, Jeong SH, Lee K. Carbapenem-resistant Acinetobacter baumannii. Korean J Clin Microbiol. 2012. 15: 1-8.   DOI
8 Baugh S, Phillips CR, Ekanayaka AS, Piddock LJ, Webber MA. Inhibition of multidrug efflux as a strategy to prevent biofilm formation. J Antimicrob Chemother. 2014. 69: 673-681.   DOI
9 Chan BCL, Han XQ, Lui SL, Wong CW, Wang TB, Cheung DW, et al. Combating against methicillin-resistant Staphylococcus aureus-two fatty acids from purslane (Portulaca oleracea L.) exhibit synergistic effects with erythromycin. J Pharm Pharmacol. 2015. 67: 107-116.   DOI
10 Fernandez L, Hancock R. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2013. 25: 661-681.   DOI
11 Wayne PA, Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-second Informational Supplement. CLSI Document. 2012. M100-S122.
12 Marchand I, Damier-Piolle L, Courvalin P, Lambert T. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother. 2004. 48: 3298-3304.   DOI
13 Amabile-Cuevas CF, Arredondo-Garcia JL, Cruz A, Rosas I. Fluoroquinolone resistance in clinical and environmental isolates of Escherichia coli in Mexico City. J Appl Microbiol. 2010. 108: 158-162.   DOI
14 Batirel A, Balkan II, Karabay O, Agalar C, Akalin S, Alici O, et al. Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections. Eur J Clin Microbiol Infect Dis. 2014. 33: 1311-1322.   DOI
15 Ni W, Li Y, Guan J, Zhao J, Cui J, Wang R, et al. Effects of efflux pump inhibitors on colistin resistance in multidrug-resistant gram-negative bacteria. Antimicrob Agents Chemother. 2016. 60: 3215-3218.   DOI
16 Park SY, Lee EJ, Kim T, Yu SN, Park KH, Lee MS, et al. Early administration of appropriate antimicrobial agents to improve the outcome of carbapenem-resistant Acinetobacter baumannii complex bacteraemic pneumonia. Int J Antimicrob Agents. 2018. 51: 407-412.   DOI
17 Shigemura K, Osawa K, Kato A, Tokimatsu I, Arakawa S, Shirakawa T, et al. Association of overexpression of efflux pump genes with antibiotic resistance in Pseudomonas aeruginosa strains clinically isolated from urinary tract infection patients. J Antibiot. 2015. 68: 568.   DOI
18 Jassim KA, Ghaima KK, Saadedin SMK. AdeABC Efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect. 2016. 3: 40898.   DOI
19 Lin MF, Lin YY, Tu CC, Lan CY. Distribution of different efflux pump genes in clinical isolates of multidrug-resistant Acinetobacter baumannii and their correlation with antimicrobial resistance. J Microbiol Immunol Infect. 2017. 50: 224-231.   DOI
20 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001. 25: 402-408.   DOI
21 Nikaido H. Multidrug Resistance in Bacteria. Annu Rev Biochem. 2009. 78: 119-146.   DOI
22 Kim YA, Park YS. Epidemiology and treatment of antimicrobialresistant gram-negative bacteria in Korea. Korean J Intern Med. 2018. 33: 247-255.   DOI
23 Xing L, Barnie PA, Su Z, Xu H. Development of efflux pumps and inhibitors (EPIs) in A. baumannii. Clin Microbiol. 2014. 3: 135.
24 Okada U, Yamashita E, Neuberger A, Morimoto M, van Veen HW, Murakami S. Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii. Nat Commun. 2017. 8: 1336.   DOI
25 Ostad Asadolah-Malayeri H, Hakemi-Vala M, Davari K. Role of AdeRs and OXA23 genes among imipenem resistant Acinetobacter baumannii isolates from two hospitals of Tehran, Iran. Iran J Pathol. 2016. 11: 345.
26 Pages JM, Masi M, Barbe J. Inhibitors of efflux pumps in Gramnegative bacteria. Trends Mol Med. 2005. 11: 382-389.   DOI
27 Grkovic S, Brown MH, Skurray RA. Transcriptional regulation of multidrug efflux pumps in bacteria. Semin Cell Dev Biol. 2001. 12: 225-237.   DOI
28 Hsu AJ, Tamma PD. Treatment of multidrug-resistant gram-negative infections in children. Clin Infect Dis. 2014. 58: 1439-1448.   DOI
29 Iacono M, Villa L, Fortini D, et al. Whole-genome pyrosequencing of an epidemic multidrug-resistant Acinetobacter baumannii strain belonging to the European clone II group. Antimicrob Agents Chemother. 2008. 52: 2616-2625.   DOI
30 Kim JY, Kim SH, Jeon SM, Park MS, Rhie HG, Lee BK. Resistance to fluoroquinolones by the combination of target site mutations and enhanced expression of genes for efflux pumps in Shigella flexneri and Shigella sonnei strains isolated in Korea. Clin Microbiol Infec. 2008. 14: 760-765.   DOI
31 Pogue JM, Neelakanta A, Mynatt RP, Sharma S, Lephart P, Kaye KS. Carbapenem-resistance in gram-negative bacilli and intravenous minocycline: an antimicrobial stewardship approach at the Detroit Medical Center. Clin Infect Dis. 2014. 59: S388-S393.
32 Qiu ZQ, Zhu LJ, Hou PF. Distribution of carbapenemases and efflux pump in carbopenems-resistance Acinetobacter baumannii. Peer J Preprints. 2016. 4: e2655v1.
33 Su XZ, Chen J, Mizushima T, Kuroda T, Tsuchiya T. AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters. Antimicrob Agents Chemother. 2005. 49: 4362-4364.   DOI
34 Rosales-Reyes R, Gayosso-Vazquez C, Fernandez-Vazquez JL, Jarillo-Quijada MD, Rivera-Benitez C, Santos-Preciado JI, et al. Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico. PLoS One. 2017. 12: e0182899.   DOI
35 Schumacher A, Steinke P, Bohnert JA, Akova M, Jonas D, Kern WV. Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Enterobacteriaceae other than Escherichia coli. J Antimicrob Chemother. 2006. 57: 344-348.   DOI
36 Smith MG, Gianoulis TA, Pukatzki S, et al. New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis, Genes De. 2007. 21: 601-614.   DOI
37 Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun. 2014. 453: 254-267.   DOI
38 Swick MC, Morgan-Linnell SK, Carlson KM, Zechiedrich L. Expression of multidrug efflux pump genes acrAB-tolC, mdfA, and norE in Escherichia coli clinical isolates as a function of fluoroquinolone and multidrug resistance. Antimicrob Agents Chemother. 2011. 55: 921-924.   DOI