Evidence map›Paper›PMID 41662980›Full record

ArticleInternational journal of antimicrobial agents2026

Phage resistance bidirectionally altered antibiotic susceptibility in Klebsiella pneumoniae via galE mutation.

Braira Wahid, Sue C Nang, Jinxin Zhao, Zhi Ying Kho, Meiling Han, Heidi Hoi-Yin Yu, Hasini Wickremasinghe, Phillip J Bergen, Saima Aslam, Robert T Schooley and 1 more

Abstract read
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In one paragraph

Article in International journal of antimicrobial agents, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Braira WahidDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Sue C NangDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Jinxin ZhaoDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Zhi Ying KhoDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Meiling HanDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Heidi Hoi-Yin YuDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Hasini WickremasingheDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Phillip J BergenDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Saima AslamDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Robert T SchooleyDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Jian LiDepartment of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia. Electronic address: jian.li@monash.edu.

Funding

Towards the Translation of Synergistic Phage-Polymyxin Combination Therapy against Pandrug-resistant Klebsiella pneumoniae: A Systems ApproachR21AI156766 · NIAID · MONASH UNIVERSITY · PI LI, JIAN · 2021 to 2022
$348k
NIAID NIH HHS R21 AI156766
6 · The paper itself

Abstract

objectiveMultidrug-resistant (MDR) Gram-negative bacteria, particularly Klebsiella pneumoniae, represent a significant threat to global health. Given the shortage of new antibiotics, bacteriophages (phages) offer a promising alternative. Understanding bacteria-phage interactions and resistance mechanisms is vital for optimising phage therapy. We aimed to investigate the resistance mechanism of an MDR clinical isolate, K. pneumoniae UCSD1 (designated as KpUCSD1) against a newly isolated phage ΦKpUCSD1.

methodsA phage-resistant mutant KpUCSD1R was collected at 24 h following treatment of KpUCSD1 with ΦKpUCSD1. Comparative genomic analysis identified mutations in KpUCSD1R, and complementation was conducted to evaluate the impact of these genes towards phage resistance. Spot tests and time-kill kinetics were performed to evaluate the bacterial susceptibility to ΦKpUCSD1. The role of galE in phage infection was evaluated with adsorption and lipopolysaccharide (LPS) assays.

resultsMutations were identified in ubiH and galE of KpUCSD1R and galE was crucial for phage infection, as complementing KpUCSD1R with wild-type galE restored its susceptibility to ΦKpUCSD1. The clean knockout strain, KpUCSD1ΔgalE, exhibited complete loss of phage susceptibility owing to defective phage adsorption. Further analyses revealed that mutated and loss of galE resulted in truncated LPS. Interestingly, phage resistance imposed a fitness trade-off associated with galE disruption, resulting in collateral antibiotic effects, namely increased susceptibility to aminoglycosides, chloramphenicol, and polymyxins, alongside reduced susceptibility to tetracycline and meropenem.

conclusionThis study demonstrates, for the first time, that galE mutation in K. pneumoniae diminishes phage adsorption by causing truncation of the LPS. The trade-off leads to increased susceptibility to several antibiotics, offering a potential therapeutic advantage in treating MDR infections.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBacteriophagesKlebsiella pneumoniaeDrug Resistance, Multiple, BacterialHumansLipopolysaccharidesMicrobial Sensitivity TestsMutationAnti-Bacterial AgentsBacterial ProteinsLipopolysaccharidesAntimicrobial resistancegalELipopolysaccharidesPhage adsorptionPhage therapy

Identifiers

PMID41662980
PMCPMC13420019

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.