Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross

作者：Kristin Scoggin, Rachel Lynch, Jyotsana Gupta, Aravindh Nagarajan, Maxwell Sheffield, Ahmed M. Elsaadi, Christopher G. R. Bowden, Manuchehr Aminian, Amy Peterson, L. Garry Adams, Michael Kirby, David W. Threadgill, Helene Andrews‐Polymenis · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2022 · DOI：10.1101/2022.02.07.479341 · 被引用次数：3 · 研究领域：Salmonella and Campylobacter epidemiology、Animal Nutrition and Physiology、Aquaculture disease management and microbiota

Abstract Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1 , known to reduce survival in mice after STm infections, are locate...