Powers, TuShun R 
ORCID: 0000-0003-0762-6316, Haeberle, Amanda L, Hammarlöf, Disa L ORCID: 0000-0002-8077-7615, Cundiff, Jennifer A, Predeus, Alexander V ORCID: 0000-0002-2750-1599, Hokamp, Karsten ORCID: 0000-0001-7464-2370, Hinton, Jay CD ORCID: 0000-0003-2671-6026 and Knodler, Leigh A ORCID: 0000-0002-3028-2198
(2021)
Niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of <i>Salmonella enterica</i>.
2021.01.11.426201-.
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Powers etal 2021 Intracellular niche-specific profiling reveals intra-cytosol vs intra-vacuolar transcriptome of S. Typhimurium - PLoS Path.pdf - Published version Download (5MB) | Preview |
Abstract
<jats:title>Abstract</jats:title><jats:p><jats:italic>Salmonella enterica</jats:italic> serovar Typhimurium (<jats:italic>S</jats:italic>. Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, <jats:italic>S</jats:italic>. Typhimurium colonizes epithelial cells lining the gastrointestinal tract. <jats:italic>S</jats:italic>. Typhimurium has an unusual lifestyle in epithelial cells that begins within an endocytic-derived <jats:italic>Salmonella</jats:italic>-containing vacuole (SCV), followed by escape into the cytosol, epithelial cell lysis and bacterial release. The cytosol is a more permissive environment than the SCV and supports rapid bacterial growth. The physicochemical conditions encountered by <jats:italic>S.</jats:italic> Typhimurium within the cytosol, and the bacterial genes required for cytosolic colonization, remain unknown. Here we have exploited the parallel colonization strategies of <jats:italic>S</jats:italic>. Typhimurium in epithelial cells to decipher the two niche-specific bacterial virulence programs. By combining a population-based RNA-seq approach with single-cell microscopic analysis, we identified bacterial genes/sRNAs with cytosol-specific or vacuole-specific expression signatures. Using these genes/sRNAs as environmental biosensors, we defined that <jats:italic>Salmonella</jats:italic> is exposed to iron and manganese deprivation and oxidative stress in the cytosol and zinc and magnesium deprivation in the SCV. Furthermore, iron availability was critical for optimal <jats:italic>S</jats:italic>. Typhimurium replication in the cytosol, as well as <jats:italic>entC</jats:italic>, <jats:italic>fepB</jats:italic>, <jats:italic>soxS</jats:italic> and <jats:italic>sitA-mntH</jats:italic>. Virulence genes that are typically associated with extracellular bacteria, namely <jats:italic>Salmonella</jats:italic> pathogenicity island 1 (SPI1) and SPI4, had a cytosolic-specific expression profile. Our study reveals that the cytosolic and vacuolar <jats:italic>S</jats:italic>. Typhimurium virulence gene programs are unique to, and tailored for, residence within distinct intracellular compartments. Therefore, this archetypical vacuole-adapted pathogen requires extensive transcriptional reprogramming to successfully colonize the mammalian cytosol.</jats:p><jats:sec><jats:title>Author Summary</jats:title><jats:p>Intracellular pathogens reside either within a membrane-bound vacuole or are free-living in the cytosol and their virulence programs are tailored towards survival within a particular intracellular compartment. Some bacterial pathogens (such as <jats:italic>Salmonella enterica</jats:italic>) can successfully colonize both intracellular niches, but how they do so is unclear. Here we have exploited the parallel intracellular lifestyles of <jats:italic>S. enterica</jats:italic> in epithelial cells to identify the niche-specific bacterial expression profiles and environmental cues encountered by <jats:italic>S. enterica</jats:italic>. We have also discovered bacterial genes that are required for colonization of the cytosol, but not the vacuole. Our results advance our understanding of pathogen-adaptation to alternative replication niches and highlight an emerging concept in the field of bacteria-host cell interactions.</jats:p></jats:sec>
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Genetics, Vaccine Related, Foodborne Illness, Infectious Diseases, Prevention, Emerging Infectious Diseases, Digestive Diseases, Biodefense, 2 Aetiology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Jan 2022 16:47 |
| Last Modified: | 15 Mar 2024 02:50 |
| DOI: | 10.1101/2021.01.11.426201 |
| Open Access URL: | https://journals.plos.org/plospathogens/article?id... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147891 |
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