Evidence map›Paper›PMID 42044123›Full record

ArticlePLoS neglected tropical diseases2026

A repetitive nucleotide insertion in the rplV gene is associated with in vitro resistance to azithromycin in Rickettsia typhi.

Weerawat Phuklia, Kiattawee Chowongkomon, Kaisone Padith, Koukeo Phommasone, Mayfong Mayxay, Allen L Richards, Elizabeth M Batty, Matthew T Robinson, Paul N Newton, Nicholas J White and 2 more

Abstract read
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Article in PLoS neglected tropical diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Weerawat PhukliaLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.ORCID https://orcid.org/0000-0003-1468-5138
Kiattawee ChowongkomonDepartment of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand.
Kaisone PadithLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
Koukeo PhommasoneLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
Mayfong MayxayLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
Allen L RichardsNaval Medical Research Center, Infectious Disease Directorate, Forest Glen, Maryland, United States of America.
Elizabeth M BattyNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
Matthew T RobinsonLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.
Paul N NewtonNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
Nicholas J WhiteNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
Nicholas P J DayNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
Elizabeth A AshleyLao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMurine typhus, caused by Rickettsia typhi, is a treatable febrile illness in Laos, where azithromycin treatment failure has been reported. Antibiotic susceptibility testing for Rickettsia spp. is challenging due to absence of resistant strains. We aimed to induce an azithromycin-resistant in R. typhi and investigate its genetic basis. METHODOLOGY: R. typhi Wilmington was cultured in azithromycin-containing media (R. typhiAZM), starting at a concentration of 0.0019 mg/L and gradually increased to 0.0625 mg/L. Resistant populations were selected up to 0.125 mg/L. MICs were determined using plaque assay and qPCR, and DNA sequencing was performed for rplD (L4), rplV (L22), and 23S rRNA domain V. Protein modeling of azithromycin-binding sites was conducted, and strain stability was assessed over 24 passages without azithromycin (R. typhi AZM (-)).

resultsMICs for wild type (R. typhiWT) and R. typhiAZM were 2 mg/L versus >16 mg/L (plaque assay) and 0.25 mg/L versus 8 mg/L (qPCR). A 15-nucleotides insertion (5'-AAAGGAAGAGCAACT-3') was found in the rplV of R. typhiAZM, but not other isolates. Protein modeling suggested the insertion extends the L22 loop, potentially affecting azithromycin binding site within the ribosomal exit tunnel. R. typhiAZM reverted to wild type MIC and genotype by 24 passages without azithromycin. R. typhiAZM exhibited an 8 -fold higher MIC than R. typhiWT.

conclusionRepetitive insertion in rplV was associated with azithromycin resistance and may interfere with drug binding. R. typhiAZM was unstable without selective pressure. This approach may help generate resistant strains for assay validation. The role of rplV mutations in azithromycin susceptibility warrants further investigation.

Indexed as

Anti-Bacterial AgentsAzithromycinDrug Resistance, BacterialMutagenesis, InsertionalRibosomal ProteinsRickettsia typhiAnimalsBacterial ProteinsDNA, BacterialMicrobial Sensitivity TestsModels, MolecularRNA, Ribosomal, 23SSequence Analysis, DNAAnti-Bacterial AgentsAzithromycinBacterial ProteinsDNA, BacterialRibosomal ProteinsRNA, Ribosomal, 23S

Identifiers

PMID42044123
PMCPMC13119893

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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.