Abstract:
Acinetobacter baumannii has become a major challenge to clinicians worldwide due to
its high epidemic potential and acquisition of antimicrobial resistance. This work aimed
at investigating antimicrobial resistance determinants and their context in four extensively
drug-resistant (XDR) NDM-producing A. baumannii clinical isolates collected between
July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 A. baumannii
were collected and screened for acquired carbapenemases (blaNDM, blaVIM and blaIMP) using
PCR. Four NDM producer A. baumannii isolates were identified and selected for whole-
genome sequencing, in silico multilocus sequence typing, and resistome analysis.
Antimicrobial susceptibility profiles were determined using disk diffusion and broth
microdilution tests. All blaNDM-positive A. baumannii isolates were XDR. Three isolates
belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570Pas/1701Oxf
(M20) and IC9 corresponding to ST85Pas/ST1089Oxf (M02 and M11). For the first time,
we report blaNDM-1 gene on the chromosome of an A. baumannii strain that belongs to
sequence type ST164Pas/ST1418Oxf. Together with AphA6, blaNDM-1 was bracketed by two
copies of ISAba14 in ST85Pas isolates possibly facilitating co-transfer of amikacin and
carbapenem resistance. A novel blaADC allele (blaADC-257) with an upstream ISAba1 element
was identified in M19 (ST/CC164Pas and ST1418Oxf/CC234Oxf). blaADC genes harbored by
M02 and M11 were uniquely interrupted by IS1008. Tn2006-associated blaOXA-23 was
carried by M20. blaOXA-94 genes were preceded by ISAba1 element in M02 and M11.
AbGRI3 was carried by M20 hosting the resistance genes aph(3`)-Ia, aac(6`)-Ib`, catB8,
ant(3``)-Ia, sul1, armA, msr(E), and mph(E). Nonsynonymous mutations were identified in
the quinolone resistance determining regions (gyrA and parC) of all isolates. Resistance
to colistin in M19 was accompanied by missense mutations in lpxACD and pmrABC
genes. The current study provided an insight into the genomic background of XDR phenotype in A. baumannii recovered from patients in Egypt. WGS revealed strong
association between resistance genes and diverse mobile genetic elements with novel
insertion sites and genetic organizations.
