Evidence map›Paper›PMID 41258156›Full record

ArticleParasites & vectors2025

Small excretory-secretory proteins of Acanthamoeba castellanii genotype T4 upregulate the expression of capsule-associated genes via the Rcs two-component system in Klebsiella pneumoniae.

Yen-Chu Chuang, Hsin-Yu Hsieh, Chih-Ming Tsai, Yu-Jen Wang

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Article in Parasites & vectors, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Yen-Chu ChuangSchool of Medicine, China Medical University, Taichung, Taiwan.
Hsin-Yu HsiehDepartment of Nursing, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan.
Chih-Ming TsaiDepartment of Parasitology, College of Medicine, National Cheng Kung University, Hsinchu, Taiwan.
Yu-Jen WangDepartment of Parasitology, School of Medicine, China Medical University, Taichung, Taiwan. yjwang@cmu.edu.tw.

Funding

Ministry of Health and Welfare MOHW-YFH-11319National Science and Technology Council NSTC 114-2320-B-039-071
6 · The paper itself

Abstract

backgroundOpportunistic pathogens such as Klebsiella pneumoniae and Acanthamoeba castellanii frequently coexist in environmental water bodies, where their interactions can influence bacterial pathogenicity. Our previous work demonstrated that A. castellanii genotype T4 (AcT4) can induce capsule enlargement in K. pneumoniae, suggesting that it is a potential environmental source of hypervirulent strains. However, the molecular mechanisms underlying this transformation remain unclear.

methodsWe investigated the effects of AcT4 on the capsule formation and virulence of K. pneumoniae using co-culture assays, antibiotic susceptibility testing, lactate dehydrogenase (LDH) cytotoxicity assays, and serum resistance assays. Capsule-associated gene expression (wzi, galF, rcsB, rmpA, and rmpA2) was analysed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Excretory-secretory proteins (ESPs) from AcT4 were separated into >10 kDa and <10 kDa fractions to identify active components. Ion concentrations in amoeba-conditioned media were measured to assess environmental stress factors.

resultsCo-culture with AcT4 significantly increased K. pneumoniae cytotoxicity toward A549 cells and enhanced serum resistance without altering antibiotic susceptibility. RT-qPCR revealed significant upregulation of rcsB, galF, and wzi in the induced strains, while the expression of the virulence plasmid genes rmpA/rmpA2 was absent. Amoeba-conditioned media altered ion distributions, notably increasing iron levels, and ESP fractionation revealed <10 kDa molecules as the primary drivers of capsule enlargement and wzi upregulation.

conclusionsSmall (<10 kDa) ESPs from AcT4 can induce capsule-associated gene expression in K. pneumoniae via activation of the Rcs two-component system, independent of virulence plasmids. These findings reveal a novel contact-independent mechanism by which environmental protozoa may contribute to the emergence of hypervirulent K. pneumoniae, highlighting potential public health risks from aquatic environments.

Indexed as

Acanthamoeba castellaniiBacterial CapsulesGene Expression Regulation, BacterialKlebsiella pneumoniaeProtozoan ProteinsBacterial ProteinsGenotypeHumansUp-RegulationVirulenceBacterial ProteinsProtozoan ProteinsAcanthamoeba castellaniiExcretory–secretory proteinsHypervirulent Klebsiella pneumoniaeRcs two-component system

Identifiers

PMID41258156
PMCPMC12628549

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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.