Cargando…

Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection

BACKGROUND: The key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive. METHODS: We analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infe...

Descripción completa

Detalles Bibliográficos
Autores principales: Matono, Takashi, Morita, Masatomo, Nakao, Nodoka, Teshima, Yuji, Ohnishi, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817621/
https://www.ncbi.nlm.nih.gov/pubmed/35123505
http://dx.doi.org/10.1186/s12941-022-00494-7
_version_ 1784645686309945344
author Matono, Takashi
Morita, Masatomo
Nakao, Nodoka
Teshima, Yuji
Ohnishi, Makoto
author_facet Matono, Takashi
Morita, Masatomo
Nakao, Nodoka
Teshima, Yuji
Ohnishi, Makoto
author_sort Matono, Takashi
collection PubMed
description BACKGROUND: The key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive. METHODS: We analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded. RESULTS: We analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, using whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 (O1v1) clade was distinct from that of the K1-ST23 (O1v2) clone. The virulence gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition. However, the K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp. CONCLUSIONS: The K1 genotype, rmpA, and aerobactin are prominent predictors of hvKp, suggesting that further pyogenic (metastatic) infection should be examined clinically. These findings may shed light on key hvKp virulence factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12941-022-00494-7.
format Online
Article
Text
id pubmed-8817621
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-88176212022-02-07 Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection Matono, Takashi Morita, Masatomo Nakao, Nodoka Teshima, Yuji Ohnishi, Makoto Ann Clin Microbiol Antimicrob Research BACKGROUND: The key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive. METHODS: We analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded. RESULTS: We analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, using whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 (O1v1) clade was distinct from that of the K1-ST23 (O1v2) clone. The virulence gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition. However, the K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp. CONCLUSIONS: The K1 genotype, rmpA, and aerobactin are prominent predictors of hvKp, suggesting that further pyogenic (metastatic) infection should be examined clinically. These findings may shed light on key hvKp virulence factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12941-022-00494-7. BioMed Central 2022-02-05 /pmc/articles/PMC8817621/ /pubmed/35123505 http://dx.doi.org/10.1186/s12941-022-00494-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Matono, Takashi
Morita, Masatomo
Nakao, Nodoka
Teshima, Yuji
Ohnishi, Makoto
Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title_full Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title_fullStr Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title_full_unstemmed Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title_short Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection
title_sort genomic insights into virulence factors affecting tissue-invasive klebsiella pneumoniae infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817621/
https://www.ncbi.nlm.nih.gov/pubmed/35123505
http://dx.doi.org/10.1186/s12941-022-00494-7
work_keys_str_mv AT matonotakashi genomicinsightsintovirulencefactorsaffectingtissueinvasiveklebsiellapneumoniaeinfection
AT moritamasatomo genomicinsightsintovirulencefactorsaffectingtissueinvasiveklebsiellapneumoniaeinfection
AT nakaonodoka genomicinsightsintovirulencefactorsaffectingtissueinvasiveklebsiellapneumoniaeinfection
AT teshimayuji genomicinsightsintovirulencefactorsaffectingtissueinvasiveklebsiellapneumoniaeinfection
AT ohnishimakoto genomicinsightsintovirulencefactorsaffectingtissueinvasiveklebsiellapneumoniaeinfection