Complete Genome Sequencing of Acinetobacter baumannii AC1633 and Acinetobacter nosocomialis AC1530 Unveils a Large Multidrug-Resistant Plasmid Encoding the NDM-1 and OXA-58 Carbapenemases

• Published in: mSphere Vol. 6; no. 1
• Main Authors: Alattraqchi, Ahmed Ghazi, Mohd Rani, Farahiyah, A Rahman, Nor Iza, Ismail, Salwani, Cleary, David W, Clarke, Stuart C, Yeo, Chew Chieng
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 27-01-2021
• Subjects: Acinetobacter - drug effects; Acinetobacter - genetics; Acinetobacter baumannii - drug effects; Acinetobacter baumannii - genetics; beta-Lactamases - genetics; Clinical Science and Epidemiology; Drug Resistance, Multiple, Bacterial - genetics; Plasmids; Research Article; Tetracycline Resistance - genetics; Whole Genome Sequencing - methods; NDM-1; Acinetobacter baumannii; carbapenem resistance; Acinetobacter nosocomialis; Tn125; pdif modules; plasmids; OXA-58
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/MSPHERE.01076-20

Carbapenem-resistant
spp. are considered priority drug-resistant human-pathogenic bacteria. The genomes of two carbapenem-resistant
spp. clinical isolates obtained from the same tertiary hospital in Terengganu, Malaysia, namely,
AC1633 and
AC1530, were sequenced. Both isolates were found to harbor the carbapenemase genes
and
in a large (ca. 170 kb) plasmid designated pAC1633-1 and pAC1530, respectively, that also encodes genes that confer resistance to aminoglycosides, sulfonamides, and macrolides. The two plasmids were almost identical except for the insertion of IS
and an IS
family element in pAC1633-1, and IS
along with
toxin-antitoxin genes flanked by inversely orientated p
(XerC/XerD) recombination sites in pAC1530. The
gene was encoded in a Tn
composite transposon structure flanked by IS
, whereas
was flanked by IS
and IS
downstream and a partial IS
element upstream within a p
module. The presence of conjugative genes in plasmids pAC1633-1/pAC1530 and their discovery in two distinct species of
from the same hospital are suggestive of conjugative transfer, but mating experiments failed to demonstrate transmissibility under standard laboratory conditions. Comparative sequence analysis strongly inferred that pAC1633-1/pAC1530 was derived from two separate plasmids in an IS
-mediated recombination or transposition event.
AC1633 also harbored three other plasmids designated pAC1633-2, pAC1633-3, and pAC1633-4. Both pAC1633-3 and pAC1633-4 are cryptic plasmids, whereas pAC1633-2 is a 12,651-bp plasmid of the GR8/GR23 Rep3-superfamily group that encodes the
(
) tetracycline resistance determinant in a p
module.
Bacteria of the genus
are important hospital-acquired pathogens, with carbapenem-resistant
listed by the World Health Organization as the one of the top priority pathogens. Whole-genome sequencing of carbapenem-resistant
AC1633 and
AC1530, which were isolated from the main tertiary hospital in Terengganu, Malaysia, led to the discovery of a large, ca. 170-kb plasmid that harbored genes encoding the New Delhi metallo-β-lactamase-1 (NDM-1) and OXA-58 carbapenemases alongside genes that conferred resistance to aminoglycosides, macrolides, and sulfonamides. The plasmid was a patchwork of multiple mobile genetic elements and comparative sequence analysis indicated that it may have been derived from two separate plasmids through an IS
-mediated recombination or transposition event. The presence of such a potentially transmissible plasmid encoding resistance to multiple antimicrobials warrants vigilance, as its spread to susceptible strains would lead to increasing incidences of antimicrobial resistance.