ORCID Profile
0000-0002-2710-2846
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Publisher: Public Library of Science (PLoS)
Date: 30-08-2021
DOI: 10.1371/JOURNAL.PPAT.1009280
Abstract: Salmonella enterica serovar Typhimurium ( S . Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, S . Typhimurium colonizes epithelial cells lining the gastrointestinal tract. S . Typhimurium has an unusual lifestyle in epithelial cells that begins within an endocytic-derived Salmonella -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 S . Typhimurium within the epithelial cytosol, and the bacterial genes required for cytosolic colonization, remain largely unknown. Here we have exploited the parallel colonization strategies of S . 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 with cytosol-induced or vacuole-induced expression signatures. Using these genes as environmental biosensors, we defined that Salmonella is exposed to oxidative stress and iron and manganese deprivation in the cytosol and zinc and magnesium deprivation in the SCV. Furthermore, iron availability was critical for optimal S . Typhimurium replication in the cytosol, as well as entC , fepB , soxS , mntH and sitA . Virulence genes that are typically associated with extracellular bacteria, namely Salmonella pathogenicity island 1 (SPI1) and SPI4, showed increased expression in the cytosol compared to vacuole. Our study reveals that the cytosolic and vacuolar S . Typhimurium virulence gene programs are unique to, and tailored for, residence within distinct intracellular compartments. This archetypical vacuole-adapted pathogen therefore requires extensive transcriptional reprogramming to successfully colonize the mammalian cytosol.
Publisher: Wiley
Date: 15-08-2022
DOI: 10.1111/MMI.14970
Abstract: Salmonella enterica spp. produce siderophores to bind iron with high affinity and can also use three xenosiderophores secreted by other microorganisms, ferrichrome, coprogen, and ferrioxamine. Here we focused on FoxA, a TonB‐dependent transporter of ferrioxamines. Adjacent to foxA is a gene annotated as a helix‐turn‐helix (HTH) domain‐containing protein, SL0358 ( foxR ), in the Salmonella enterica serovar Typhimurium SL1344 genome. FoxR shares homology with transcriptional regulators belonging to the AraC/XylS family. foxR is syntenic with foxA in the Enterobacteriaceae family, suggesting their functional relatedness. Both foxA and foxR are repressed by the ferric uptake regulator (Fur) under iron‐rich growth conditions. When iron is scarce, FoxR acts as a transcriptional activator of foxA by directly binding to its upstream regulatory region. A point mutation in the HTH domain of FoxR abolished this binding, as did mutation of a direct repeat motif in the foxA upstream regulatory region. Desferrioxamine (DFOE) enhanced FoxR protein stability and foxA transcription but did not affect the affinity of FoxR binding to the foxA regulatory region. In summary, we have identified FoxR as a new member of the AraC/XylS family that regulates xenosiderophore‐mediated iron uptake by S . Typhimurium and likely other Enterobacteriaceae members.
No related grants have been discovered for Zeus Saldana Ahuactzi.