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Peer-reviewedCC BY 4.0iMeta

Different gut microbiome dysbioses impact the evolutionary fate of hypervirulent Klebsiella pneumoniae

  • Carey Lim1,2
  • Jialing Zheng3
  • Guoxiang Cheam1,2
  • Melvin Yong1,2
  • Hanrong Chen4
  • Andrew Ting4
  • Yahua Chen1,2
  • Qingqing Wang3
  • Niranjan Nagarajan1,4
  • Yunn‐Hwen Gan1,2
4 affiliations
  1. 1Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore
  2. 2Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore
  3. 3Institute of Immunology Zhejiang University School of Medicine, Hangzhou, and Liangzhu Laboratory Hangzhou China
  4. 4Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR) Singapore Republic of Singapore
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Abstract

The intestinal microbiota acts as a barrier against pathogen colonization, yet how specific ecological perturbations shape the evolutionary fate of invading pathogens remains unclear. Here, we show that the mode of gut perturbation and type of dysbiosis determine whether hypervirulent Klebsiella pneumoniae (hvKp) persist or clear from the intestines. Transient ampicillin exposure creates a permissive, low‐diversity intestinal niche dominated by facultative anaerobes, which supports long‐term, high‐density hvKp colonization. The dysbiotic state creates an altered redox environment to favor these oxygen‐using bacteria and is associated with the rapid emergence of hypomucoid variants. This occurs via contractions in the poly‐T tract in the promoter of the rmpA regulator that controls capsule hypermucoviscosity, as well as mutations in the poly‐G tract within the coding sequence. This evolutionary trajectory reflects a virulence‐persistence trade‐off in high‐nutrient, low‐competition environment. Conversely, osmotic perturbation via laxative treatment elicits only a transient window of colonization‐susceptibility that is rapidly closed by the recovery of a Bacteroides‐enriched community that is consistent with their ability to actively suppress pathogen colonization via short‐chain fatty acids (SCFAs). Furthermore, SCFAs such as butyrate are more effective in inhibiting hypomucoid rmpA variants relative to wild‐type bacteria, providing a possible explanation for how an osmotically perturbed gut microbiome constrains the expansion of these mutants. These findings provide insights into how transient antibiotic exposure could potentially drive long‐term intestinal pathobiont colonization while laxative‐induced osmotic perturbations do not rewire the energy and metabolic landscape of the gut microbiome, enabling rapid recovery and colonization resistance despite an initial plunge in diversity. Our work reveals that the specific mode of perturbation affects the trajectory for pathogen adaptation, and highlights the potential role of commensal competition in constraining pathogen evolution.

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Cite

BibTeXRIS
BibTeX
@article{lim2026different,
  title = {{Different gut microbiome dysbioses impact the evolutionary fate of hypervirulent Klebsiella pneumoniae}},
  author = {Carey Lim and Jialing Zheng and Guoxiang Cheam and Melvin Yong and Hanrong Chen and Andrew Ting and Yahua Chen and Qingqing Wang and Niranjan Nagarajan and Yunn‐Hwen Gan},
  journal = {iMeta},
  year = {2026},
  month = sep,
  doi = {10.1002/imt2.70175},
  url = {https://doi.org/10.1002/imt2.70175},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Different gut microbiome dysbioses impact the evolutionary fate of hypervirulent Klebsiella pneumoniae
AU  - Carey Lim
AU  - Jialing Zheng
AU  - Guoxiang Cheam
AU  - Melvin Yong
AU  - Hanrong Chen
AU  - Andrew Ting
AU  - Yahua Chen
AU  - Qingqing Wang
AU  - Niranjan Nagarajan
AU  - Yunn‐Hwen Gan
PY  - 2026
DA  - 2026/09/23
JO  - iMeta
DO  - 10.1002/imt2.70175
UR  - https://doi.org/10.1002/imt2.70175
AB  - The intestinal microbiota acts as a barrier against pathogen colonization, yet how specific ecological perturbations shape the evolutionary fate of invading pathogens remains unclear. Here, we show that the mode of gut perturbation and type of dysbiosis determine whether hypervirulent Klebsiella pneumoniae (hvKp) persist or clear from the intestines. Transient ampicillin exposure creates a permissive, low‐diversity intestinal niche dominated by facultative anaerobes, which supports long‐term, high‐density hvKp colonization. The dysbiotic state creates an altered redox environment to favor these oxygen‐using bacteria and is associated with the rapid emergence of hypomucoid variants. This occurs via contractions in the poly‐T tract in the promoter of the rmpA regulator that controls capsule hypermucoviscosity, as well as mutations in the poly‐G tract within the coding sequence. This evolutionary trajectory reflects a virulence‐persistence trade‐off in high‐nutrient, low‐competition environment. Conversely, osmotic perturbation via laxative treatment elicits only a transient window of colonization‐susceptibility that is rapidly closed by the recovery of a Bacteroides‐enriched community that is consistent with their ability to actively suppress pathogen colonization via short‐chain fatty acids (SCFAs). Furthermore, SCFAs such as butyrate are more effective in inhibiting hypomucoid rmpA variants relative to wild‐type bacteria, providing a possible explanation for how an osmotically perturbed gut microbiome constrains the expansion of these mutants. These findings provide insights into how transient antibiotic exposure could potentially drive long‐term intestinal pathobiont colonization while laxative‐induced osmotic perturbations do not rewire the energy and metabolic landscape of the gut microbiome, enabling rapid recovery and colonization resistance despite an initial plunge in diversity. Our work reveals that the specific mode of perturbation affects the trajectory for pathogen adaptation, and highlights the potential role of commensal competition in constraining pathogen evolution.
SN  - 2770-5986
SN  - 2770-596X
ER  -