Meropenem-induced cross-protection in Salmonella enterica resistant variants: Insights from adaptive laboratory evolution and whole genome sequencing

Tavares da Silva, Ruthchelly ; García-Penas, Ivo (Universidad de Zaragoza) ; Espina, Laura ; García-Gonzalo, Diego (Universidad de Zaragoza) ; Magnani, Marciane ; Pagán, Rafael (Universidad de Zaragoza)

Resumen: Adaptive laboratory evolution (ALE) assay provides a deep understanding of the genetic mechanisms and processes involved in bacterial responses. This study aimed to obtain resistant-variants (RVs) of Salmonella enterica subsp. enterica Typhimurium (SeT) and Enteritidis (SeE) after ALE assays with meropenem (MPM); to identify genetic modifications of RVs responsible for their increased resistance; and to evaluate their cross-protection against antibiotics and food preservatives (heat and carvacrol). Five MPM-RVs from SeT (SeT_M1-5) and one from SeE (SeE_M5) showed a 100 % increase in MPM minimum inhibitory concentrations (from 0.0312 to 0.0625 μg/mL). MPM-RVs had lower maximum growth rates and/or longer lag times, except in SeT_M5 and SeE_M3, which maintained or even improved growth fitness in the presence of MPM. Whole genome sequencing of RVs revealed single mutations in AMR-related and -unrelated genes in most MPM-RVs: spoT in SeT_M1, glnA in SeT_M2, thrS in SeT_M4 and SeE_M2, and mrdA in SeT_M5, SeE_M3 and SeE_M5. Two mutations were identified in SeT_M3 and SeE_M4: spoT and znuA in SeT_M3 and AWJ12_RS14025 and rfbF in SeE_M4. The individual mutations resulted in cross-protection to at least one of the antibiotics tested and/or heat (reductions of up to 3.8–4.3 cycles of inactivation for MPM-RVs in contrast to 4.7 and 5.3 cycles for SeE and SeT, respectively) and/or carvacrol (3.4–3.7 cycles for MPM-RVs in contrast to 4.4 cycles for SeT). These findings highlight the importance of preventing the emergence of resistant bacterial variants, considering the cross-protection to other antibiotics and food preservatives, which plays an important role in spreading resistance in food chain.

Idioma: Inglés

DOI: 10.1016/j.fm.2025.104823

Año: 2025

Publicado en: FOOD MICROBIOLOGY 132 (2025), 104823 [12 pp.]
ISSN: 0740-0020

Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2021-123404NB-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Tecnología de Alimentos (Dpto. Produc.Animal Cienc.Ali.)