Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2021.05.24
  • Accepted : 2021.06.28
  • Published : 2021.06.30
Download PDF
⟨ Previous Next ⟩

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

Acknowledgement

This work was done with research funds from the Ministry Education, Republic of Korea through the National Research Foundation (NRF) grant funded by the South Korea government (2019R1C1C1004820) and Catholic University of Pusan (2019).

References

  1. 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. https://doi.org/10.1111/j.1365-2672.2009.04401.x
  2. Bae IK, Jeong SH, Lee K. Carbapenem-resistant Acinetobacter baumannii. Korean J Clin Microbiol. 2012. 15: 1-8. https://doi.org/10.5145/KJCM.2012.15.1.1
  3. 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. https://doi.org/10.1007/s10096-014-2070-6
  4. 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. https://doi.org/10.1093/jac/dkt420
  5. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015. 13: 42-51. https://doi.org/10.1038/nrmicro3380
  6. 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. https://doi.org/10.1111/jphp.12315
  7. Coyne S, Courvalin P, Perichon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother. 2011. 55.3: 947-953. https://doi.org/10.1128/AAC.01388-10
  8. Fernandez L, Hancock R. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2013. 25: 661-681. https://doi.org/10.1128/CMR.00043-12
  9. Grkovic S, Brown MH, Skurray RA. Transcriptional regulation of multidrug efflux pumps in bacteria. Semin Cell Dev Biol. 2001. 12: 225-237. https://doi.org/10.1006/scdb.2000.0248
  10. Hsu AJ, Tamma PD. Treatment of multidrug-resistant gram-negative infections in children. Clin Infect Dis. 2014. 58: 1439-1448. https://doi.org/10.1093/cid/ciu069
  11. 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. https://doi.org/10.1128/AAC.01643-07
  12. Jassim KA, Ghaima KK, Saadedin SMK. AdeABC Efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect. 2016. 3: 40898. https://doi.org/10.17795/ajcmi-40898
  13. 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. https://doi.org/10.1111/j.1469-0691.2008.02033.x
  14. Kim YA, Park YS. Epidemiology and treatment of antimicrobialresistant gram-negative bacteria in Korea. Korean J Intern Med. 2018. 33: 247-255. https://doi.org/10.3904/kjim.2018.028
  15. 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. https://doi.org/10.1016/j.jmii.2015.04.004
  16. 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. https://doi.org/10.1006/meth.2001.1262
  17. 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. https://doi.org/10.1128/AAC.48.9.3298-3304.2004
  18. 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. https://doi.org/10.1128/AAC.00248-16
  19. Nikaido H. Multidrug Resistance in Bacteria. Annu Rev Biochem. 2009. 78: 119-146. https://doi.org/10.1146/annurev.biochem.78.082907.145923
  20. 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. https://doi.org/10.1038/s41467-017-01399-2
  21. 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.
  22. Pages JM, Masi M, Barbe J. Inhibitors of efflux pumps in Gramnegative bacteria. Trends Mol Med. 2005. 11: 382-389. https://doi.org/10.1016/j.molmed.2005.06.006
  23. 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. https://doi.org/10.1016/j.ijantimicag.2017.10.018
  24. Peleg AY, Adams J, Paterson DL. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2007. 51: 2065-2069. https://doi.org/10.1128/AAC.01198-06
  25. 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.
  26. Qiu ZQ, Zhu LJ, Hou PF. Distribution of carbapenemases and efflux pump in carbopenems-resistance Acinetobacter baumannii. Peer J Preprints. 2016. 4: e2655v1.
  27. 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. https://doi.org/10.1128/AAC.00584-09
  28. 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. https://doi.org/10.1371/journal.pone.0182899
  29. 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. https://doi.org/10.1093/jac/dki446
  30. 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.
  31. 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. https://doi.org/10.1038/ja.2015.34
  32. 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. https://doi.org/10.1101/gad.1510307
  33. 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. https://doi.org/10.1128/AAC.00748-09
  34. 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. https://doi.org/10.1128/AAC.49.10.4362-4364.2005
  35. Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun. 2014. 453: 254-267. https://doi.org/10.1016/j.bbrc.2014.05.090
  36. 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. https://doi.org/10.1128/AAC.00996-10
  37. Wayne PA, Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-second Informational Supplement. CLSI Document. 2012. M100-S122.
  38. Xing L, Barnie PA, Su Z, Xu H. Development of efflux pumps and inhibitors (EPIs) in A. baumannii. Clin Microbiol. 2014. 3: 135.