AUTHOR=Carrasco Letícia Dias de Melo , Dabul Andrei Nicoli Gebieluca , Boralli Camila Maria dos Santos , Righetto Gabriela Marinho , Carvalho Iago Silva e , Dornelas Janaína Valerini , Martins da Mata Camila Pacheco Silveira , Araújo César Augusto de , Leite Edna Mariléa Meireles , Lincopan Nilton , Camargo Ilana Lopes Baratella da Cunha 

TITLE=Polymyxin Resistance Among XDR ST1 Carbapenem-Resistant Acinetobacter baumannii Clone Expanding in a Teaching Hospital

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.622704

DOI=10.3389/fmicb.2021.622704

ISSN=1664-302X

ABSTRACT=<p><italic>Acinetobacter baumannii</italic> is an opportunistic pathogen primarily associated with multidrug-resistant nosocomial infections, for which polymyxins are the last-resort antibiotics. This study investigated carbapenem-resistant <italic>A. baumannii</italic> strains exhibiting an extensively drug-resistant (XDR) phenotype, including four isolates considered locally pan drug-resistant (<sub>L</sub>PDR), isolated from inpatients during an outbreak at a teaching hospital in Brazil. ApaI DNA macrorestriction followed by PFGE clustered the strains in three pulsotypes, named A to C, among carbapenem-resistant <italic>A. baumannii</italic> strains. Pulsotypes A and B clustered six polymyxin-resistant <italic>A. baumannii</italic> strains. MLST analysis of representative strains of pulsotypes A, B, and C showed that they belong, respectively, to sequence types ST1 (clonal complex, CC1), ST79 (CC79), and ST903. Genomic analysis of international clones ST1 and ST79 representative strains predicted a wide resistome for β-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, with <italic>bla</italic><sub><italic>OXA–23</italic></sub> and <italic>bla</italic><sub><italic>OXA–72</italic></sub> genes encoding carbapenem resistance. Amino acid substitutions in PmrB (Thr232Ile or Pro170Leu) and PmrC (Arg125His) were responsible for polymyxin resistance. Although colistin MICs were all high (MIC ≥ 128 mg/L), polymyxin B MICs varied; strains with Pro170Leu substitution in PmrB had MICs &gt; 128 mg/L, while those with Thr232Ile had lower MICs (16–64 mg/L), irrespective of the clone. Although the first identified polymyxin-resistant <italic>A. baumannii</italic> strain belonged to ST79, the ST1 strains were endemic and caused the outbreak most likely due to polymyxin B use. The genome comparison of two ST1 strains from the same patient, but one susceptible and the other resistant to polymyxin, revealed mutations in 28 ORFs in addition to <italic>pmrBC</italic>. The ORF codifying an acyl-CoA dehydrogenase has gained attention due to its fatty acid breakdown and membrane fluidity involvement. However, the role of these mutations in the polymyxin resistance mechanism remains unknown. To prevent the dissemination of XDR bacteria, the hospital infection control committee implemented the patient bathing practice with a 2% chlorhexidine solution, a higher concentration than all <italic>A. baumannii</italic> chlorhexidine MICs. In conclusion, we showed the emergence of polymyxin resistance due to mutations in the chromosome of the carbapenem-resistant <italic>A. baumannii</italic> ST1, a high-risk global clone spreading in this hospital.</p>