doi:10.1016/j.foodres.2025.116330engCampillo, RaúlGarcía-Penas, IvoLópez, NoeliaSánchez, AnaFau, AlbertoGómez, DiegoBerdejo, DanielGarcía-Gonzalo, DiegoPagán, RafaelCiprofloxacin-resistant Salmonella Typhimurium demonstrates cross-tolerance to heat treatments in liquid food matricesART-2025-144044The alarming occurrence of antimicrobial resistance (AMR) in human bacterial isolates indicates that prevention and control protocols are not adequately managing this global threat. The agri-food chain plays a noteworthy role in the dissemination of AMR via the handling and consumption of contaminated food products. However, it remains unclear whether acquisition of AMR in bacteria might indirectly enhance bacterial tolerance to food preservation methods (i.e., cross-tolerance), resulting in defective pathogen reduction. In this study, five ciprofloxacin (CIP) resistant variants (RVs) were generated after exposing Salmonella Typhimurium LT2 (SeT) to an upward CIP gradient. We thereupon observed up to 125-fold increases in the minimum inhibitory concentration to CIP in all five RVs. Moreover, two RVs showed reduced sensitivity to heat in laboratory media compared to SeT. The most tolerant strain displayed mutations in genes previously implicated in AMR, coding for RNA polymerase subunits (rpoD), regulatory protein RamR (ramR) and enzyme adenylate cyclase (cyaA). Validation in liquid food matrices revealed enhanced thermotolerance of the RV to treatments performed at 50 °C in orange juice (×986.7 survival risk after 15 min of treatment), and 54 °C in milk (more than ×10,000 survival risk after 30 min) and liquid-whole egg (×976.7 survival risk after 40 min). Furthermore, virulence assays in nematode Caenorhabditis elegans showed mutations conferring AMR and cross-tolerance did not result in a substantial loss of pathogenicity. Hence, exposures to CIP might lead to the selection of S. Typhimurium variants that pose limits to heat treatment efficacy, thereby increasing their survival risk and ultimately allowing them to reach the end consumer – thus also limiting the scope of antibiotic action during eventual infection.2025http://zaguan.unizar.es/record/16085710.1016/j.foodres.2025.116330http://zaguan.unizar.es/record/160857oai:zaguan.unizar.es:160857info:eu-repo/grantAgreement/ES/MCIU/PID2021-123404NB-I00Food Research International 210 (2025), 116330 [13 pp.]byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess