Pham, R. | bioRxiv Science

bioRxiv2025

Stress tolerance of multiple Salmonella enterica strains associated with foodborne outbreaks

Salmonella enterica is a foodborne pathogen commonly found in food processing environments. While control methods such as heat treatment and sanitizers are often used, S. enterica has evolved strategies for survival and persistence to overcome pathogen control. This study assessed 43 outbreak-associated (OA) and non-outbreak associated (NOA) S. enterica isolates from serovars Enteritidis, Heidelberg, Newport, Typhimurium, and monophasic Typhimurium (I 4,[5],12:i:-) for enhanced stress tolerance. Heat shock at 56{degrees} C, minimum inhibitory concentrations (MICs) for sanitizers sodium hypochlorite (NaOCl) and peracetic acid (PAA), and crystal violet microtiter assays were used to evaluate heat tolerance, sanitizer tolerance, and attachment capacity, respectively. Most isolates (n =34/43) carried at least one antimicrobial resistance gene, and nearly half (n =21/43) displayed genotypic and/or phenotypic resistance to ampicillin, ciprofloxacin, or ceftriaxone. Most isolates carried genes conferring resistance to gold (n =43/43) and arsenic (n= 41/43), and tolerance to mercury, copper, and silver was common among monophasic Typhimurium and Heidelberg isolates. Efflux pump qacEdelta1 was detected among eight Heidelberg isolates. We found enhanced stress tolerance (i.e. an unusually high ability to survive and adapt to various environmental stresses) to sanitizers and enhanced attachment capacity, indicating biofilm formation. Isolates evaluated for heat tolerance survived at least 15 min at 56{degrees} C and three survived >60 min. Overall, we found evidence of enhanced tolerance to individual stresses across both OA and NOA S. enterica. There were no strong patterns based upon serovar or OA/NOA status; however, we did find that specific enhanced stress tolerance profiles may have contributed to outbreak characteristics.

microbiology↗

bioRxiv2024

CDC42 Inhibitors Alter Patterns of Vessel Arborization in Skin and Tumors in vivo

Tumors that arise in the epidermis must develop a vascular supply to grow beyond a millimeter in depth. This process requires CDC42 GTPases such as CDC42, RhoJ and RhoQ. Despite this dependence on angiogenesis for growth, melanoma tumors are minimally responsive to current anti-angiogenesis agents, highlighting the need for more effective drugs in this class. Here we integrate antibody infusion, optical tissue clearing, multiphoton imaging, and three-dimensional semi-automated tracing to develop a quantitative approach to measure changes in vascular architecture in skin and skin tumors. This new approach uncovered differences in vessel arborization in the skin of RhoJ KO mice as compared to wild-type mice. Furthermore, novel small molecules that inhibit CDC42 GTPases inhibited both tumor growth and vessel branching within tumors to a similar degree as Braf inhibitors, which are commonly used to treat melanoma. In contrast to Braf inhibitors, however, which only affected tumor vasculature, CDC42 inhibitors affected vascularization in both tumor and normal skin without apparent toxicity to endothelial or stromal cells. These novel CDC42 inhibitors similarly blocked vessel branching in human cell-based micro-physiological models of normal and tumor vessels. RNA sequencing revealed reduced expression of multiple angiogenesis-related genes in drug-treated skin. Taken together, these studies identify a new class of pharmacologic agents that inhibit vessel branching in both normal skin and tumors with potential utility for treating skin cancer and skin diseases characterized by pathologic angiogenesis.

cancer biology↗