Characterisation of mcr-4.3 in a colistin-resistant Acinetobacter nosocomialis clinical isolate from Cape Town, South Africa

dc.contributor.authorSnyman, Yolandien_ZA
dc.contributor.authorReuter, Sandraen_ZA
dc.contributor.authorWhitelaw, Andrew Christopheren_ZA
dc.contributor.authorStein, Lisaen_ZA
dc.contributor.authorMaloba, Motlatji Reratilwe Bonnieen_ZA
dc.contributor.authorNewton-Foot, Maeen_ZA
dc.date.accessioned2021-08-19T10:35:18Z
dc.date.available2021-08-19T10:35:18Z
dc.date.issued2021
dc.descriptionCITATION: Snyman, Y., et al. 2021. Characterisation of mcr-4.3 in a colistin-resistant Acinetobacter nosocomialis clinical isolate from Cape Town, South Africa. Journal of Global Antimicrobial Resistance, 25:102-106, doi:10.1016/j.jgar.2021.03.002.
dc.descriptionThe original publication is available at https://www.sciencedirect.com
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractObjectives: Colistin resistance in Acinetobacter spp. is increasing, resulting in potentially untreatable noso- comial infections. Plasmid-mediated colistin resistance is of particular concern due to its low fitness cost and potential transferability to other bacterial strains and species. This study investigated the colistin resistance mechanism in a clinical Acinetobacter nosocomialis isolate from Cape Town, South Africa. Methods: A colistin-resistant A. nosocomialis isolate was identified from a blood culture in 2017. PCR and Illumina whole-genome sequencing (WGS) were performed to identify genes and mutations conferring resistance to colistin. Plasmid sequencing was performed on an Oxford Nanopore platform. mcr function- ality was assessed by broth microdilution after cloning the mcr gene into pET-48b( + ) and expressing it in SHuffle®T7 Escherichia coli and after curing the plasmid using 62.5 mg/L acridine orange. Results: The colistin minimum inhibitory concentration (MIC) of the A. nosocomialis isolate was 16 mg/L. The mcr-4.3 gene was detected by PCR and WGS. No other previously described colistin resistance mech- anism was found by WGS. The mcr-4.3 gene was identified on a 24 024-bp RepB plasmid (pCAC13a). Functionality studies showed that recombinant mcr-4.3 did not confer colistin resistance in E. coli. How- ever, plasmid curing of pCAC13a restored colistin susceptibility in A. nosocomialis . Conclusion: We describe the first detection of a plasmid-mediated mcr-4.3 gene encoding colistin re- sistance in A. nosocomialis and the first detection of mcr-4.3 in a clinical isolate in Africa. Recombinant expression of mcr-4.3 did not confer colistin resistance in E. coli , suggesting that its functionality may be RepB plasmid-dependent or species-specific.en_ZA
dc.description.urihttps://www.sciencedirect.com/science/article/pii/S2213716521000679
dc.description.versionPublisher's version
dc.format.extent5 pagesen_ZA
dc.identifier.citationSnyman, Y., et al. 2021. Characterisation of mcr-4.3 in a colistin-resistant Acinetobacter nosocomialis clinical isolate from Cape Town, South Africa. Journal of Global Antimicrobial Resistance, 25:102-106, doi:10.1016/j.jgar.2021.03.002
dc.identifier.issn2213-7165 (online)
dc.identifier.otherdoi:10.1016/j.jgar.2021.03.002
dc.identifier.urihttp://hdl.handle.net/10019.1/110889
dc.language.isoen_ZAen_ZA
dc.publisherElsevieren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectPolymyxin resistanceen_ZA
dc.subjectAcinetobacteren_ZA
dc.subjectNosocomial infectionsen_ZA
dc.subjectDrug resistanceen_ZA
dc.subjectColistinen_ZA
dc.titleCharacterisation of mcr-4.3 in a colistin-resistant Acinetobacter nosocomialis clinical isolate from Cape Town, South Africaen_ZA
dc.typeArticleen_ZA
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