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Colistin and Carbapenem-Resistant Acinetobacter baumannii Aci46 in Thailand: Genome Analysis and Antibiotic Resistance Profiling.

ABSTRACT: Resistance to the last-line antibiotics against invasive Gram-negative bacterial infection is a rising concern in public health. Multidrug resistant (MDR) Acinetobacter baumannii Aci46 can resist colistin and carbapenems with a minimum inhibitory concentration of 512 µg/mL as determined by microdilution method and shows no zone of inhibition by disk diffusion method. These phenotypic characteristics prompted us to further investigate the genotypic characteristics of Aci46. Next generation sequencing was applied in this study to obtain whole genome data. We determined that Aci46 belongs to Pasture ST2 and is phylogenetically clustered with international clone (IC) II as the predominant strain in Thailand. Interestingly, Aci46 is identical to Oxford ST1962 that previously has never been isolated in Thailand. Two plasmids were identified (pAci46a and pAci46b), neither of which harbors any antibiotic resistance genes but pAci46a carries a conjugational system (type 4 secretion system or T4SS). Comparative genomics with other polymyxin and carbapenem-resistant A. baumannii strains (AC30 and R14) identified shared features such as CzcCBA, encoding a cobalt/zinc/cadmium efflux RND transporter, as well as a drug transporter with a possible role in colistin and/or carbapenem resistance in A. baumannii. Single nucleotide polymorphism (SNP) analyses against MDR ACICU strain showed three novel mutations i.e., Glu229Asp, Pro200Leu, and Ala138Thr, in the polymyxin resistance component, PmrB. Overall, this study focused on Aci46 whole genome data analysis, its correlation with antibiotic resistance phenotypes, and the presence of potential virulence associated factors.

SUBMITTER: Thadtapong N

PROVIDER: S-EPMC8468411 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWith an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.MethodsPatients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.ResultsTwenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.ConclusionsColistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Project description:BackgroundMultidrug-resistant Acinetobacter baumannii is an important causal pathogen of healthcare-associated infections, and colistin-resistant strains have recently emerged owing to the increased use of colistin. Using next-generation sequencing (NGS), a single whole-genome sequencing (WGS) protocol can identify and type pathogens, analyze genetic relationships among different pathogens, predict pathogenic transmissions, and detect antibiotic resistance genes. However, only a few studies have applied NGS in studying the resistance mechanism and epidemiology of colistin-resistant A. baumannii. This study aimed to elucidate the resistance mechanism of colistin-resistant A. baumannii and analyze its molecular epidemiology through WGS.Materials and methodsThe subjects in this study were patients who visited a university hospital between 2014 and 2018. Thirty colistin-resistant strains with high minimum inhibitory concentrations were selected from various patient samples, and WGS was performed. Comparative genomic analysis was performed for the 27 colistin-resistant A. baumannii strains using a colistin-susceptible strain as the reference genome.ResultsThe WGS analysis found no mutation for lpxA, lpxC, lpx D, pmrA, pmrB, and mcr1, the genes known to be associated with colistin resistance. Fifty-seven coding sequences (CDS) showed differences; they included 13 CDS with known names and functions that contained 21 genes. From the whole-genome multi-locus sequence typing (wgMLST) and single nucleotide polymorphism (SNP) analyses, two major clusters were found for the colistin-resistant A. baumannii strains. However, no differences were observed by the time of detection for each cluster, the samples, the pattern of antibiotic resistance, or the patient characteristics. In the conventional MLST following the Oxford scheme, the typing result showed ST1809, ST451, ST191, ST1837, and ST369 in the global clone 2 (GC2), without any relation with the results of wgMLST and SNP analyses.ConclusionBased on the findings of the resistance gene analysis through WGS and comparative genomic analysis, the potential genes associated with colistin-resistance or CDS were examined. Furthermore, the analysis of molecular epidemiology through WGS regarding colistin-resistant A. baumannii may prove helpful in preventing infection by multidrug-resistant bacteria and controlling healthcare-associated infections.

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Colistin and Carbapenem-Resistant Acinetobacter baumannii Aci46 in Thailand: Genome Analysis and Antibiotic Resistance Profiling.

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