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Multiple Interspecies Recombination Events Documented by Whole-genome Sequencing in Multidrug-resistant Clinical Isolates

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Specialty Microbiology
Date 2024 Mar 14
PMID 38482359
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Abstract

Introduction: () was long known as an easy-to-treat bacterium, but increasing resistance against beta-lactams and other critically important antibiotics is now a growing concern. We describe here the whole-genome sequencing (WGS) analysis of three non-typeable isolates received in 2018-2019 by the Belgian National Reference Centre (NRC) for , as they presented an unusual multi-resistant profile.

Methods: All three isolates were sequenced by WGS and mapped to the reference isolate Rd KW20. Shorten uptake signal sequences (USSs) known to be associated with homologous recombination were sought in and genes, and inner partial sequences were compared against the blast nucleotide database to look for similarity with other species. Their antimicrobial resistance (AMR) genotype was studied. Core-genome multilocus sequence typing (MLST) was performed on the NTHi database pubMLST to place our isolates in the actual worldwide epidemiology.

Results: The isolates also harboured interspecies recombination patterns in the region involved in cell wall synthesis. The three isolates were multidrug resistant and two of them were also resistant to amoxicillin-clavulanic acid and showed a reduced susceptibility to meropenem. All three isolates belonged to the MLST clonal complex (CC) 422, and WGS revealed that the three were very similar. They harboured mobile genetic elements (carrying , and genes associated with resistance), mutations in and linked to fluoroquinolone resistance as well as remodelling events in that might be related to lower carbapenem susceptibility.

Conclusion: The evolution towards antimicrobial multiresistance (AMR) is a complex and poorly understood phenomenon, although probably linked to a large degree to the presence of USSs and exchange within the family . To better understand the respective roles of clonal expansion, horizontal gene transfers, spontaneous mutations and interspecies genetic rearrangements in shaping AMR, both analysis of communities over time within individuals and worldwide monitoring of non-typeable causing infections should be conducted.

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