Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica

• DOI: 10.1371/journal.ppat.1009280
• Publication Date: 2021-08-30T17:33:15Z
• Authors: TuShun R. Powers; Amanda L. Haeberle; Alexander V. Predeus; Disa L. Hammarlöf; Jennifer A. Cundiff; Zeus Saldaña-Ahua...; Karsten Hokamp; Jay C. D. Hinton; Leigh A. Knodler
• Keywords: Salmonella enterica; Intracellular parasite

Salmonella enterica serovar Typhimurium ( S . Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, colonizes epithelial cells lining the gastrointestinal tract. has an unusual lifestyle begins within endocytic-derived -containing vacuole (SCV), followed by escape into cytosol, cell lysis bacterial release. The cytosol more permissive environment than SCV supports rapid growth. physicochemical conditions encountered genes required for cytosolic colonization, remain largely unknown. Here we have exploited parallel colonization strategies of to decipher two niche-specific virulence programs. By combining population-based RNA-seq approach with single-cell microscopic analysis, identified cytosol-induced or vacuole-induced expression signatures. Using these as environmental biosensors, defined exposed oxidative stress iron manganese deprivation zinc magnesium SCV. Furthermore, availability was critical optimal replication well entC , fepB soxS mntH sitA Virulence are typically associated extracellular bacteria, namely pathogenicity island 1 (SPI1) SPI4, showed increased compared vacuole. Our study reveals vacuolar gene programs unique to, tailored for, residence distinct intracellular compartments. This archetypical vacuole-adapted therefore requires extensive transcriptional reprogramming successfully colonize mammalian cytosol.