In Vivo Selection of Pan-Drug Resistant Acinetobacter baumannii during Antibiotic Treatment
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Purpose: Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediatedby a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC,and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumanniiis not well understood. Materials and Methods: We investigated the genotypicand phenotypic changes that underlie pan-drug resistance mechanisms by determiningdifferences between the alterations in extensively drug-resistant (XDR)A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart(AB003) recovered from one patient before and after antibiotic treatment, respectively. Results: All three clinical isolates shared an identical sequence type(ST138), belonging to the global epidemic clone, clonal complex 92, and all producedOXA-23 carbapenemase. The PDR AB003 showed two genetic differences,acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene,relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC,or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-timeof flight analysis, the three isolates commonly showed two major peaks at 1728 m/zand 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detectedonly in the PDR A. baumannii AB003 isolate. Conclusion: Our results showthat changes in lipid A structure via a mutation in the pmrB gene and acquisition ofarmA gene might confer resistance to colistin and aminoglycosides to XDR A. baumanniistrains, resulting in appearance of a PDR A. baumannii strain of ST138.
Abstract
Purpose: Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediatedby a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC,and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumanniiis not well understood. Materials and Methods: We investigated the genotypicand phenotypic changes that underlie pan-drug resistance mechanisms by determiningdifferences between the alterations in extensively drug-resistant (XDR)A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart(AB003) recovered from one patient before and after antibiotic treatment, respectively. Results: All three clinical isolates shared an identical sequence type(ST138), belonging to the global epidemic clone, clonal complex 92, and all producedOXA-23 carbapenemase. The PDR AB003 showed two genetic differences,acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene,relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC,or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-timeof flight analysis, the three isolates commonly showed two major peaks at 1728 m/zand 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detectedonly in the PDR A. baumannii AB003 isolate. Conclusion: Our results showthat changes in lipid A structure via a mutation in the pmrB gene and acquisition ofarmA gene might confer resistance to colistin and aminoglycosides to XDR A. baumanniistrains, resulting in appearance of a PDR A. baumannii strain of ST138.
참고문헌 (33)
- Magiorakos AP, "Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance", Clin Microbiol Infect, 18, pp.268~281 (2012)
- Chang HL, "Nosocomial outbreak of infection with multidrug-resistant Acinetobacter baumannii in a medical center in Taiwan", Infect Control Hosp Epidemiol, 30, pp.34~38 (2009)
- Maragakis LL, "Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options", Clin Infect Dis, 46, pp.1254~1263 (2008)
- Cho HH, "Spread and genetic characterization of ST137 and ST138 multidrug-resistant Acinetobacter baumannii isolated from a tertiary hospital in Korea", Ann Clin Lab Sci, 43, pp.145~150 (2013)
- Endo S, "Molecular epidemiology of carbapenem-non-susceptible Acinetobacter baumannii in Japan", J Antimicrob Chemother, 67, pp.1623~1626 (2012)
- Lee Y, "Carbapenem-nonsusceptible Acinetobacter baumannii of sequence type 92 or its single-locus variants with a G428T substitution in zone 2 of the rpoB gene", J Antimicrob Chemother, 66, pp.66~72 (2011)
- Wang X, "Clonal diversity of Acinetobacter baumannii clinical isolates revealed by a snapshot study", BMC Microbiol, 13, pp.234~ (2013)
- Cai Y, "Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies", J Antimicrob Chemother, 67, pp.1607~1615 (2012)
- 이경원, "Multidrug-Resistant Acinetobacter spp.: Increasingly Problematic Nosocomial Pathogens", Yonsei Medical Journal, 52(6), pp.879~891 (2011), 연세대학교의과대학
- O’Hara JA, "Activities of vancomycin-containing regimens against colistin-resistant Acinetobacter baumannii clinical strains", Antimicrob Agents Chemother, 57, pp.2103~2108 (2013)
- Valencia R, "Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital", Infect Control Hosp Epidemiol, 30, pp.257~263 (2009)
- Adams MD, "Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system", Antimicrob Agents Chemother, 53, pp.3628~3634 (2009)
- Moffatt JH, "Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production", Antimicrob Agents Chemother, 54, pp.4971~4977 (2010)
- La Scola B, "Sequencing of the rpoB gene and flanking spacers for molecular identification of Acinetobacter species", J Clin Microbiol, 44, pp.827~832 (2006)
- Clinical and Laboratory Standards Institute, "Performance standards for antimicrobial susceptibility testing: twenty-second informational supplement, M100-S22", Clinical and Laboratory Standards Institute, ~ (2012)
- Bartual SG, "Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii", J Clin Microbiol, 43, pp.4382~4390 (2005)
- Tenover FC, "Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing", J Clin Microbiol, 33, pp.2233~2239 (1995)
- Cho YJ, "Genetic basis of resistance to aminoglycosides in Acinetobacter spp. and spread of armA in Acinetobacter baumannii sequence group 1 in Korean hospitals", Diagn Microbiol Infect Dis, 64, pp.185~190 (2009)
- Vila J, "Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii", J Antimicrob Chemother, 39, pp.757~762 (1997)
- Vila J, "Mutation in the gyrA gene of quinolone-resistant clinical isolates of Acinetobacter baumannii", Antimicrob Agents Chemother, 39, pp.1201~1203 (1995)
- Woodford N, "Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp", Int J Antimicrob Agents, 27, pp.351~353 (2006)
- Lin YC, "Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan", Antimicrob Agents Chemother, 54, pp.2078~2084 (2010)
- Beceiro A, "Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system", Antimicrob Agents Chemother, 55, pp.3370~3379 (2011)
- Yi EC, "Rapid isolation method for lipopolysaccharide and lipid A from gram-negative bacteria", Analyst, 125, pp.651~656 (2000)
- Petrosillo N, "Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies", Clin Microbiol Infect, 14, pp.816~827 (2008)
- López-Rojas R, "Acinetobacter baumannii resistant to colistin alters its antibiotic resistance profile: a case report from Spain", J Infect Dis, 204, pp.1147~1148 (2011)
- López-Rojas R, "Colistin resistance in a clinical Acinetobacter baumannii strain appearing after colistin treatment: effect on virulence and bacterial fitness", Antimicrob Agents Chemother, 57, pp.4587~4589 (2013)
- Arroyo LA, "The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A", Antimicrob Agents Chemother, 55, pp.3743~3751 (2011)
- Gunn JS, "The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more", Trends Microbiol, 16, pp.284~290 (2008)
- Gunn JS, "PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance", Mol Microbiol, 27, pp.1171~1182 (1998)
- Zhou Z, "Lipid A modifications in polymyxin-resistant Salmonella typhimurium:PMRA-dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation", J Biol Chem, 276, pp.43111~43121 (2001)
- Kim Y, "In vivo emergence of colistin resistance in Acinetobacter baumannii clinical isolates of sequence type 357 during colistin treatment", Diagn Microbiol Infect Dis, 79, pp.362~366 (2014)
- Gordon NC, "Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance", Int J Antimicrob Agents, 35, pp.219~226 (2010)