Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

Chen, Y, Brook, T, Soe, CZ, O'Neill, I, Alcon-Giner, C, Leelastwattanagul, O, Phillips, S, Caim, S, Clarke, P, Hall, L and Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, 2020. Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors. Microbial Genomics. ISSN 2057-5858

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Abstract

Klebsiella spp. are frequently enriched in the gut microbiota of preterm neonates, and overgrowth is associated with necrotizing enterocolitis (NEC), nosocomial infections and late-onset sepsis. Little is known about the genomic and phenotypic characteristics of preterm-associated Klebsiella as previous studies have focussed on recovery of antimicrobial-resistant isolates or culture independent molecular analyses. The aim of this study was to better characterize preterm-associated Klebsiella populations using phenotypic and genotypic approaches. Faecal samples from a UK cohort of healthy and sick preterm neonates (n=109) were screened on MacConkey agar to isolate lactose positive Enterobacteriaceae. Whole-genome sequences were generated for Klebsiella spp., and virulence and antimicrobial resistance genes identified. Antibiotic susceptibility profiling, and in vitro macrophage and iron assays were undertaken for the Klebsiella strains. Metapangenome analyses with a manually curated genome dataset were undertaken to examine diversity of Klebsiella oxytoca and related bacteria in a publicly available shotgun metagenome dataset. Approximately one-tenth of faecal samples harboured Klebsiella spp. (Klebsiella pneumoniae, 7.3 %; Klebsiella quasipneumoniae, 0.9 %; Klebsiella grimontii, 2.8 %; Klebsiella michiganensis, 1.8 %). Isolates recovered from NEC- and sepsis-affected infants and those showing no signs of clinical infection (i.e. 'healthy') encoded multiple -lactamases. No difference was observed between isolates recovered from ‘healthy’ and sick infants with respect to in vitro siderophore production (all encoded enterobactin in their genomes). All K. pneumoniae, K. quasipneumoniae, K. grimontii and K. michiganensis faecal isolates tested were able to reside and persist in macrophages, indicating their immune evasion abilities. Metapangenome analyses of published metagenomic data confirmed our findings regarding the presence of K. michiganensis in the preterm gut. There is little difference in the phenotypic and genomic characteristics of Klebsiella isolates recovered from 'healthy' and sick infants. Identification of -lactamases in all isolates may prove problematic when defining treatment regimens for NEC or sepsis, and suggests ‘healthy’ preterm infants contribute to the resistome. Refined analyses with curated sequence databases are required when studying closely related species present in metagenomic data.

Item Type:	Journal article
Publication Title:	Microbial Genomics
Creators:	Chen, Y., Brook, T., Soe, C.Z., O'Neill, I., Alcon-Giner, C., Leelastwattanagul, O., Phillips, S., Caim, S., Clarke, P., Hall, L. and Hoyles, L.
Publisher:	Microbiology Society
Date:	21 May 2020
ISSN:	2057-5858
Identifiers:	Number Type 10.1099/mgen.0.000377 DOI 1318363 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	29 Apr 2020 09:18
Last Modified:	26 May 2020 14:18
URI:	https://irep.ntu.ac.uk/id/eprint/39758

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