Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Major Endemic Clones in South America

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistant (XDR). The aim of this study was to characterize the resistance mechanisms presented by 18 carbapenem-resistant A. baumannii isolates from five different Brazilian hospitals. Species identification was determined by rpoB sequencing, and antimicrobial susceptibility was determined by broth microdilution. Isolates were submitted to whole genome sequencing using Illumina platform and genetic similarity was determined by PFGE, MLST, and cgMLST. Genome analysis was used to identify intrinsic and acquired resistance determinants, including mutations in the AdeRSABC efflux system and in outer membrane proteins (OMPs). All isolates were identified as A. baumannii and grouped into 4 pulsotypes by PFGE, which belonged to clonal complexes (CC) 15Pas/103Ox (n = 4) and 79Pas/113Ox (n = 14), corresponding to IC4 and IC5, respectively. High MIC values to carbapenems, broad-spectrum cephalosporins, amikacin, and ciprofloxacin were observed in all isolates, while MICs of ampicillin/sulbactam, gentamicin, and tigecycline varied among the isolates. Minocycline was the most active antimicrobial agent tested. Moreover, 12 isolates (66.7%) were considered resistant to polymyxins. Besides intrinsic OXA-51 and ADC variants, all isolates harbored an acquired carbapenem-hydrolyzing class D β-lactamase (CHDL) encoding gene, either blaOXA–23 or blaOXA–72. A diversity of aminoglycoside modifying enzymes and resistance determinants to other antimicrobial classes were found, as well as mutations in gyrA and parC. Non-synonymous mutations have also been identified in the AdeRSABC efflux system and in most OMPs, but they were considered natural polymorphisms. Moreover, resistance to polymyxins among isolates belonging to IC5 were associated to non-synonymous mutations in pmrB, but no known polymyxin resistance mechanism was identified in isolates belonging to IC4. In conclusion, A. baumannii clinical isolates belonging to South America’s major clones present a myriad of antimicrobial resistance determinants. Special attention should be paid to natural polymorphisms observed in each clonal lineage, especially regarding non-synonymous mutations in constitutive genes associated with distinct resistance phenotypes.

WGS-Based Analysis of Carbapenem-Resistant Acinetobacter baumannii in Vietnam and Molecular Characterization of Antimicrobial Determinants and MLST in Southeast Asia

“…The prevalence of MDR/CRAb was very high. The results are in agreement with previous reports: most CRAb strains display resistance to at least one compound in three or more antimicrobial categories and are designated as MDR [ 6 , 7 ]. Resistance against imipenem was seen in 91.6% of XDR A. baumannii strains isolated from patients in three hospitals in southern Vietnam between 2012 and 2014 [ 17 ].…”

“…Five strains appeared in three different clusters, and six strains were unique singletons. WGS showed a higher discriminatory power than conventional typing methods [ 6 ]. It allows a more precise trackback analysis of the strains, particularly when analyzing carbapenem-resistant A. baumannii isolates, which threaten the global healthcare system.…”

“…The treatment of carbapenem-resistant A. baumannii (CRAb) is becoming a global challenge. CRAb is emerging worldwide, and the majority of these isolates often show MDR or XDR patterns [ 6 , 7 ]. They are also associated with an increased length of stay at hospital ICUs [ 8 ].…”

Diversity of International High-Risk Clones of Acinetobacter baumannii Revealed in a Russian Multidisciplinary Medical Center during 2017–2019

“…Eight international clones were defined earlier [ 17 ], and the ninth was introduced recently [ 18 ]. The first three clones (IC1–IC3) are distributed worldwide, with IC1 and IC2 also known as global clones (GC), while the rest were sometimes defined as regional, or even endemic clones [ 13 , 20 , 21 , 22 ].…”

“…Although many reports consider different clones or lineages of A. baumannii species to be associated with particular parts or regions of the world [ 13 , 20 , 21 , 22 ], the dramatically fast distribution of SARS-CoV-2 in 2020 has demonstrated that our knowledge regarding the spread of different pathogens is still limited.…”