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Acquisition of Tn6018-3′ CS regions increases colistin MICs against Acinetobacter baumannii isolates harboring new variants of AbaRs

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A Correction to this article was published on 07 November 2017

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Abstract

Colistin is the last hope to treat extensively drug resistance (XDR) Acinetobacter baumannii (A. baumannii) infections, but resistance to colistin is currently reported in clinical centers all over the world. Here, we studied two colistin-resistant A. baumannii isolates with a difference in minimum inhibitory concentrations (MICs) that were isolated from a single burn patient during treatment in the hospitalization period. The international clonal (IC) lineage, multilocus sequence typing (MLST), and multiple loci variable number tandem repeat (VNTR) analysis (MLVA) typing were used to characterize the relatedness of A. baumannii isolates. Lipopolysaccharides (LPS) and PmrAB system analysis by PCR sequencing, polyacrylamide gel electrophoresis (PAGE), and real-time PCR were performed to determine the intactness and probable modifications of the LPS as the main resistance mechanisms to colistin. A combination of PCR, sequencing, and restriction fragment length polymorphism (RFLP) was used for A. baumannii resistance islands (AbaR) mapping as resistance-determinant reservoirs. Two isolates were identical at all MLST and VNTR marker loci that indicated the isolates were the same strain. In comparison to colistin-heteroresistant A. baumannii strain TEH267 (MIC = 1.5 mg/L), colistin-resistant A. baumannii strain TEH273 (MIC ≥256 mg/L) acquired two genomic regions including Tn6018-topA sequence and topA sequence-3′ CS in its AbaR structure containing ispA and cadA genes which, it would appear, could be associated with eightfold increase in colistin MIC. Both isolates had new variants of AbaR-like structures which could be derivatives of the typical AbaR3. According to the results of this study, AbaRs could be associated with an increase in MIC to colistin.

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  • 07 November 2017

    The published online version of this article contained a mistake. The correct affiliation of Alireza Ekrami should have been “Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran” . The authors regret this error.

References

  • Adams MD, Nickel GC, Bajaksouzian S, Lavender H, Murthy AR, Jacobs MR, Bonomo RA (2009) Resistance to colistin in Acinetobacter baumannii associated with mutations in the pmrAB two component system. Antimicrob Agents Chemother 53:3628–3634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahador A, Taheri M, Pourakbari B, Hashemizadeh Z, Rostami H, Mansoori N, Raoofian R (2013) Emergence of rifampicin, tigecycline, and colistin-resistant Acinetobacter baumannii in Iran; spreading of MDR strains of novel international clone variants. Microb Drug Resist 19:397–406

    Article  CAS  PubMed  Google Scholar 

  • Bahador A, Raoo An R, Farshadzadeh Z, Beitollahi L, Khaledi A, Rahimi S, Mokhtaran M, Mehrabi Tavana A, Esmaeili D (2015) The prevalence of ISAba 1 and ISAba 4 in Acinetobacter baumannii species of different international clone lineages among patients with burning in Tehran, Iran. Jundishapur J Microbiol 8:e17167

    Article  PubMed  PubMed Central  Google Scholar 

  • Bartual SG, Seifert H, Hippler C, Luzon MA, Wisplinghoff H, Rodríguez Valera F (2005) Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii. J Clin Microbiol 43:4382–4390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, Dhanji H, Chart H, Bou G, Livermore DM, Woodford N (2011) Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 55:3370–3379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Y, Chai D, Wang R, Liang B, Bai N (2012) Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother 67:1607–1615

    Article  CAS  PubMed  Google Scholar 

  • Cheah SE, Li J, Tsuji BT, Forrest A, Bulitta JB, Nation RL (2016) Colistin and polymyxin B dosage regimens against Acinetobacter baumannii: differences in activity and the emergence of resistance. Antimicrob Agents Chemother 60(7):3921–3933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faber F, Egli T, Harder W (1993) Transient repression of the synthesis of OmpF and aspartate transcarbamoylase in Escherichia coli K12 as a response to pollutant stress. FEMS Microbiol Lett 111:189–195

    Article  CAS  PubMed  Google Scholar 

  • Gallagher LA, Ramage E, Weiss EJ, Radey M, Hayden HS, Held KG, Huse HK, Zurawski DV, Brittnacher MJ, Manoil C (2015) Resources for genetic and genomic analysis of emerging pathogen Acinetobacter baumannii. J Bacteriol 197:2027–2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higgins PG, Lehmann M, Wisplinghoff H, Seifert H (2010) gyrB multiplex PCR to differentiate between Acinetobacter calcoaceticus and Acinetobacter genomic species 3. J Clin Microbiol 48:4592–4594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karaha N, Sundsfjord A, Townerc K, Samuelsena Ø (2012) Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii. Drug Resist Updat 15:237–247

    Article  Google Scholar 

  • Kishii R, Takei M (2009) Relationship between the expression of ompF and quinolone resistance in Escherichia coli. J Infect Chemother 15:361–366

    Article  CAS  PubMed  Google Scholar 

  • Krizova L, Dijkshoorn L, Nemec A (2011) Diversity and evolution of AbaR genomic resistance islands in Acinetobacter baumannii strains of European clone I. Antimicrob Agents Chemother 55:3201–3206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lesho E, Yoon EJ, McGann P, Snesrud E, Kwak Y, Milillo M, Onmus-Leone F, Preston L, St Clair K, Nikolich M, Viscount H, Wortmann G, Zapor M, Grillot-Courvalin C, Courvalin P, Clifford R, Waterman PE (2013) Emergence of colistin-resistance in extremely drug-resistant Acinetobacter baumannii containing a novel pmrCAB operon during colistin therapy of wound infections. J Infect Dis 208:1142–1151

    Article  CAS  PubMed  Google Scholar 

  • Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, Liolios L (2006) Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 50(9):2946–2950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168

    Article  PubMed  Google Scholar 

  • Mac Síomóin RA, Nakata N, Murai T, Yoshikawa M, Tsuji H, Sasakawa C (1996) Identification and characterization of ispA, a Shigella flexneri chromosomal gene essential for normal in vivo cell division and intracellular spreading. Mol Microbiol 19:599–609

    Article  PubMed  Google Scholar 

  • Magiorakos AP, Srinivasan A, Carey R, Carmeli Y, Falagas MF, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug resistant, extensively drug-resistant and pandrug- resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281

    Article  CAS  PubMed  Google Scholar 

  • Moffatt JH, Harper M, Harrison P, Hale JDF, Vinogradov E, Seemann T, Henry R, Crane B, Michael F, Cox AD, Ben Adler B, Nation RL, Li J, Boyce JD (2010) Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother 54:4971–4977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moradi J, Hashemi BF, Bahador A (2015) Antibiotic resistance of Acinetobacter baumannii in Iran: a systemic review of the published literature. Osong Public Health Res Perspect 6:79–86

    Article  PubMed  PubMed Central  Google Scholar 

  • Pagano M, Martins AF, Barth AL (2016) Mobile genetic elements related to carbapenem resistance in Acinetobacter baumannii. Braz J Microbiol. doi:10.1016/j.bjm.2016.06.005

    PubMed  PubMed Central  Google Scholar 

  • Park YK, Choi JY, Shin D, Ko KS (2011) Correlation between overexpression and amino acid substitution of the PmrAB locus and colistin resistance in Acinetobacter baumannii. Int J Antimicrob Agents 37:525–530

    Article  CAS  PubMed  Google Scholar 

  • Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA (2007) Global challenge of multidrug resistant Acinetobacter baumannii. Antimicrob Agents Chemother 51:3471–3484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poirel L, Bonnin RA, Nordmann P (2011) Genetic basis of antibiotic resistance in pathogenic Acinetobacter species. IUBMB Life 63:1061–1067

    Article  CAS  PubMed  Google Scholar 

  • Post V, White PA, Hall RM (2010) Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii. J Antimicrob Chemother 65:1162–1170

    Article  CAS  PubMed  Google Scholar 

  • Pourcel C, Minandri F, Hauck Y, D’Arezzo S, Imperi F, Vergnaud G, Visca P (2011) Identification of variable-number tandem-repeat (VNTR) sequences in Acinetobacter baumannii and interlaboratory validation of an optimized multiple-locus VNTR analysis typing scheme. J Clin Microbiol 49:539–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qureshi ZA, Hittle LE, O’Hara JA, Rivera JI, Syed A, Shields RK, Pasculle AW, Ernst RK, Doi Y (2015) Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance. Clin Infect Dis 60:1295–1303

    Article  PubMed  PubMed Central  Google Scholar 

  • Sepahvand V, Davarpanah MA, Hejazi SH (2015) Epidemiology of colistin-resistant Acinetobacter baumannii in Shiraz, Iran. J Appl Environ Biol Sci 5:45–48

    Google Scholar 

  • Stokes HW, Gillings MR (2011) Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens. FEMS Microbiol Rev 35:790–819

    Article  CAS  PubMed  Google Scholar 

  • Turton JF, Gabriel SN, Valderrey C, Kaufmann ME, Pitt TL (2007) Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii. Clin Microbiol Infect 13:807–815

    Article  CAS  PubMed  Google Scholar 

  • Valencia R, Arroyo LA, Conde M, Aldana JM, Torres MJ, Fernández-Cuenca F, Garnacho-Montero J, Cisneros JM, Ortíz C, Pachón J, Aznar J (2003) Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect Control Hosp Epidemiol 30:257–263

    Article  Google Scholar 

  • Viehman JA, Nguyen MH, Doi Y (2014) Treatment options for carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii infections. Drugs 74:1315–1333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber DJ, Rutala WA, Miller MB, Huslage K, Sickbert-Bennett E (2010) Role of hospital surfaces in the transmission of emerging health care-associated pathogens: norovirus, Clostridium difficile, and Acinetobacter species. Am J Infect Control 38:S25–S33

    Article  PubMed  Google Scholar 

  • Zahedi Bialvaei A, Samadi Kafil H (2015) Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin 31:707–721

    Article  Google Scholar 

Download references

Acknowledgements

We thank Lenka Krizova, Lenie Dijkshoorn, and Alexandr Nemec for providing Acinetobacter baumannii strain NIPH321 that we used as positive control for AbaR3.

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Correspondence to Abbas Bahador.

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This research has been supported by Tehran University of Medical Sciences & Health Services, Grant No. 93-04-103-27532.

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We have none to declare.

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A correction to this article is available online at https://doi.org/10.1007/s12223-017-0560-5.

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Savari, M., Ekrami, A., Shoja, S. et al. Acquisition of Tn6018-3′ CS regions increases colistin MICs against Acinetobacter baumannii isolates harboring new variants of AbaRs. Folia Microbiol 62, 373–379 (2017). https://doi.org/10.1007/s12223-017-0507-x

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