Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia.

Wyres, K. L.; Nguyen, T. N.; Lam, M. M.; Judd, L. M.; van Vinh Chau, N.; Dance, D. A.; Ip, M.; Karkey, A.; Ling, C. L.; Miliya, T.; Newton, P.; Nguyen, L.; Sengduangphachanh, A.; Turner, P.; Veeraraghavan, B.; Voong Vinh, P.; Vongsouvath, M.; Thomson, N. R.; Baker, S.; Holt, K. E.

doi:10.1101/557785

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bioRxiv · 10.1101/557785

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia.

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Abstract

BackgroundK. pneumoniae is a leading cause of blood stream infection (BSI). Strains producing extended spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial resistant (AMR) K. pneumoniae, and also for the characteristically antimicrobial sensitive, community-acquired hypervirulent strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. MethodsWe conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate. FindingsK. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common amongst South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes amongst K. pneumoniae. InterpretationSouth and Southeast Asia are high-risk regions for the emergence of AMR and convergent AMR-hypervirulent K. pneumoniae. Enhanced surveillance efforts, reporting STs, AMR and virulence information are urgently required to monitor this public health threat. FundingThis work was supported by the Wellcome Trust (grant #206194 to Wellcome Sanger Institute) and the Bill and Melinda Gates Foundation, Seattle (grant OPP1175797 to KEH). KEH is supported by a Senior Medical Research Fellowship from the Viertel Foundation of Australia. DAB and PNN are supported by the Wellcome Trust.

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Wyres, K. L., Nguyen, T. N., Lam, M. M., Judd, L. M., van Vinh Chau, N., Dance, D. A., Ip, M., Karkey, A., Ling, C. L., Miliya, T., Newton, P., Nguyen, L., Sengduangphachanh, A., Turner, P., Veeraraghavan, B., Voong Vinh, P., Vongsouvath, M., Thomson, N. R., Baker, S., Holt, K. E.. 2019-02-26. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia.. https://doi.org/10.1101/557785

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