High Genetic Diversity of Carbapenem-Resistant Acinetobacter baumannii Isolates Recovered in Nigerian Hospitals in 2016 to 2020

Abstract

Acinetobacter baumannii causes difficult-to-treat infections mostly among immunocompromised patients. Clinically relevant A. baumannii lineages and their carbapenem resistance mechanisms are sparsely described in Nigeria. This study aimed to characterize the diversity and genetic mechanisms of carbapenem resistance among A. baumannii strains isolated from hospitals in southwestern Nigeria. We sequenced the genomes of all A. baumannii isolates submitted to Nigeria's antimicrobial resistance surveillance reference laboratory between 2016 and 2020 on an Illumina platform and performed in silico genomic characterization. Selected strains were sequenced using the Oxford Nanopore technology to characterize the genetic context of carbapenem resistance genes. The 86 A. baumannii isolates were phylogenetically diverse and belonged to 35 distinct Oxford sequence types (^oxfSTs), 16 of which were novel, and 28 Institut Pasteur STs (^pasSTs). Thirty-eight (44.2%) isolates belonged to none of the known international clones (ICs). Over 50% of the isolates were phenotypically resistant to 10 of 12 tested antimicrobials. The majority (n = 54) of the isolates were carbapenem resistant, particularly the IC7 (^pasST25; 100%) and IC9 (^pasST85; >91.7%) strains. bla_OXA-23 (34.9%) and bla_NDM-1 (27.9%) were the most common carbapenem resistance genes detected. All bla_OXA-23 genes were carried on Tn2006 or Tn2006-like transposons. Our findings suggest that a 10-kb Tn125 composite transposon is the primary means of bla_NDM-1 dissemination. Our findings highlight an increase in bla_NDM-1 prevalence and the widespread transposon-facilitated dissemination of carbapenemase genes in diverse A. baumannii lineages in southwestern Nigeria. We make the case for improving surveillance of these pathogens in Nigeria and other understudied settings. IMPORTANCE Acinetobacter baumannii bacteria are increasingly clinically relevant due to their propensity to harbor genes conferring resistance to multiple antimicrobials, as well as their ability to persist and disseminate in hospital environments and cause difficult-to-treat nosocomial infections. Little is known about the molecular epidemiology and antimicrobial resistance profiles of these organisms in Nigeria, largely due to limited capacity for their isolation, identification, and antimicrobial susceptibility testing. Our study characterized the diversity and antimicrobial resistance profiles of clinical A. baumannii in southwestern Nigeria using whole-genome sequencing. We also identified the key genetic elements facilitating the dissemination of carbapenem resistance genes within this species. This study provides key insights into the clinical burden and population dynamics of A. baumannii in hospitals in Nigeria and highlights the importance of routine whole-genome sequencing-based surveillance of this and other previously understudied pathogens in Nigeria and other similar settings.

Keywords: Acinetobacter baumannii; antimicrobial resistance; blaNDM-1; blaOXA-23; carbapenem resistance; genomics; surveillance.

FIG 1

Maximum likelihood phylogeny of A. baumannii isolates. Colored clades represent international clones. BUT, Babcock University Teaching Hospital, Ilishan-Remo, Ogun State; CLL, Clina-Lancet Laboratories, Victoria Island, Lagos State; ELL, EL-LAB Medical Diagnostics, Festac, Lagos State; ILO, University of Ilorin Teaching Hospital, Ilorin, Kwara State; LUT, Lagos University Teaching Hospital, Idi-Araba, Lagos State; OAU, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State; UCH, University College Hospital, Ibadan, Oyo State.

FIG 2

Comparison of the number of antimicrobial classes for which A. baumannii isolates in each lineage carried at least one resistance-conferring gene.

FIG 3

Lineage distribution and cocarriage of carbapenem resistance genes among A. baumannii isolates in southwestern Nigeria, 2016 to 2020. *, carried two copies of the bla_OXA-23 gene.

FIG 4

Tn2006 and Tn2006-like transposons carrying the bla_OXA-23 carbapenemase gene in A. baumannii isolates in southwestern Nigeria, 2016 to 2020. A complete ISAba1 unit comprises two open reading frames, both indicated with blue arrows. The two Tn2006 copies in the ^oxfST231 (~110 kb apart) and ^oxfST1114/1841 (~1.5 Mb apart) isolates are shown. Genetic contexts for lineages highlighted in the light blue box were identified based on annotated complete assemblies while the contexts for unshaded lineages were identified based on identification and annotation of the contig carrying the bla_OXA-23 gene, hence the incomplete repeat element flanks. All STs shown are Oxford STs. Corresponding Institut Pasteur STs are as follows: ^oxfST2452, ^pasST409; ^oxfST1567, ^pasST1; ^oxfST231, ^pasST1; ^oxfST1114/1841, ^pasST2; ^oxfST229, ^pasST25; ^oxfST2151, ^pasST10; ^oxfST862, ^pasST149.

FIG 5

Tn125 and Tn7382 transposons carrying the bla_NDM-1 carbapenemase gene in A. baumannii isolates in southwestern Nigeria, 2016 to 2020. Genetic contexts for lineages highlighted in the light blue box were identified based on annotated complete assemblies while the contexts for the other lineages were identified based on identification and annotation of the contig carrying the bla_NDM-1 gene, hence the incomplete repeat element flanks. All STs shown are Oxford STs. Corresponding Institut Pasteur STs are as follows: ^oxfST1089, ^pasST85; ^oxfST1936, ^pasST85; ^oxfST231, ^pasST1; ^oxfST930, ^pasST32; ^oxfST862, ^pasST149; ^oxfST2450, ^pasST1093; ^oxfST2456, ^pasST2. *, split across two contigs.