Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

Abstract

Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extendedspectrum 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. Methods: We 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, a K. pneumoniae-specific genomic typing tool. Results: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 Kloci. 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 among 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 among K. pneumoniae.Conclusions: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.

Diversity of mucoid to non-mucoid switch among carbapenemase-producing Klebsiella pneumoniae

“…S1 ), precluding the confident identification of mutations responsible for the NM phenotype. Similarly, Wyres et al were recently unable to determine the K-type of 129 out of 393 K. pneumoniae genomes sequenced by tagmentation [ 22 ]. The 72 NM variants were sequenced following enzymatic digestion of the genomic DNA by a mix of nucleases, providing a uniform coverage of the K. pneumoniae genome and no discrimination of AT-rich regions (Fig.…”

Multidrug Resistant Klebsiella pneumoniae ST101 Clone Survival Chain From Inpatients to Hospital Effluent After Chlorine Treatment

“…Additionally, the biocides resistance gene mdfA encodes resistance to quaternary-ammonium compounds, sodium hydroxide and other biocides, while merA encodes resistance to mercury. Although genes associated with resistance and virulence are usually identified in separate subpopulations of K. pneumoniae there are strains harboring both high resistance and virulence ( Lam et al, 2019 ; Wyres et al, 2020b ) making them highly pathogenic and almost impossible to treat ( Wyres et al, 2020b ).…”

Emerging carbapenem-resistant Klebsiella pneumoniae sequence type 16 causing multiple outbreaks in a tertiary hospital in southern Vietnam

“…The spread of multidrug-resistant Gram-negative bacteria is one of the most concerning issues in global health [1–3]. Among these, carbapenem-resistant Enterobacteriaceae have recently been singled out as an urgent threat to global public health by the U.S. Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO) and Public Health England (PHE) [1, 4, 5].…”

“…The mortality rates attributable to carbapenem-resistant K. pneumoniae generally range from 20 to 30 % and have reached up to 75 % in bloodstream infections among neonates [3, 14, 16, 17]. While nosocomial outbreaks caused by carbapenem-resistant K.…”