Antimicrobial efficacy and amino acid substitutions associated with susceptibility to the tellurium compound AS101 against Haemophilus influenzae and Haemophilus parainfluenzae.

Antimicrobial Haemophilus Tellurite Whole-genome sequencing

Journal

International microbiology : the official journal of the Spanish Society for Microbiology
ISSN: 1618-1905
Titre abrégé: Int Microbiol
Pays: Switzerland
ID NLM: 9816585

Informations de publication

Date de publication:
11 Jul 2024
Historique:
received: 09 06 2024
accepted: 05 07 2024
revised: 04 07 2024
medline: 11 7 2024
pubmed: 11 7 2024
entrez: 10 7 2024
Statut: aheadofprint

Résumé

The tellurite toxicity in Haemophilus influenzae and H. parainfluenzae remains unclear. To understand the potential of tellurite as a therapeutic option for these bacteria, we investigated the antimicrobial efficacy of AS101, a tellurium compound, against H. influenzae and H. parainfluenzae and the molecular basis of their differences in AS101 susceptibility. Through broth microdilution, we examined the minimum inhibitory concentration (MIC) of AS101 in 51 H. influenzae and 28 H. parainfluenzae isolates. Whole-genome sequencing was performed on the H. influenzae isolates to identify genetic variations associated with AS101 susceptibility. The MICs of AS101 were ≦ 4, 16-32, and ≧ 64 μg/mL in 9 (17.6%), 12 (23.5%), and 30 (58.8%) H. influenzae isolates, respectively, whereas ≦ 0.5 μg/mL in all H. parainfluenzae isolates, including multidrug-resistant isolates. Time-killing kinetic assay and scanning electron microscopy revealed the in vitro bactericidal activity of AS101 against H. parainfluenzae. Forty variations in nine tellurite resistance-related genes were associated with AS101 susceptibility. Logistic regression, receiver operator characteristic curve analysis, Venn diagram, and protein sequence alignment indicated that Val195Ile substitution in TerC, Ser93Gly in Gor (glutathione reductase), Pro44Ala/Ala50Pro in NapB (nitrate reductase), Val307Leu in TehA (tellurite resistance protein), Cys105Arg in CysK (cysteine synthase), and Thr364Ser in Csd (Cysteine desulfurase) were strongly associated with reduced AS101 susceptibility, whereas Ser155Pro in TehA with increased AS101 susceptibility. In conclusions, the antimicrobial efficacy of AS101 is high against H. parainfluenzae but low against H. influenzae. Genetic variations and corresponding protein changes relevant to AS101 non-susceptibility in H. influenzae were identified.

Identifiants

pubmed: 38987387
doi: 10.1007/s10123-024-00558-y
pii: 10.1007/s10123-024-00558-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Science and Technology Council, Taiwan
ID : 111-2314-B-214-003-MY3
Organisme : E-Da Hospital
ID : EDAHT111005

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Cheng-Hsun Ho (CH)

Department of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, No.8, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan. chenghsunho@gmail.com.

Tsung-Ying Yang (TY)

Department of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, No.8, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan.

Sung-Pin Tseng (SP)

Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan.

Pei-Yi Su (PY)

Department of Laboratory Medicine, E-DA Hospital, Kaohsiung, Taiwan.

Classifications MeSH