SifA-mediated Remodeling of the Salmonella-Containing Vacuole Prevents Bacterial Dormancy by Promoting Nutrient Accessibility
Valenzuela, C.; Rodriguez, F. J. G.; Mazza, T.; Gil, M.; Dotsenko, K.; Luk, C. H.; Enninga, J.
Show abstract
Salmonella exploits a range of intracellular niches within host cells, adapting to different microenvironments that support its survival and replication. This niche diversity is mediated by bacterial effectors injected via the two type 3 secretion systems (T3SS). Salmonella resides either within membrane-bound Salmonella containing vacuoles (SCV) or they grow rapidly within the cytosol upon SCV rupture. Recently, we identified a third intracellular subpopulation, dormant Salmonella within modified vacuoles in epithelial cells, which can survive for up to 7 days in vitro. To explore how bacterial effectors influence the balance of these three subpopulations, we constructed a panel of mutants lacking genes encoding key effectors and examined their intracellular behaviors at 6 and 24 hours post-infection (hpi). Deletion of the T3SS-2 effector SifA significantly increased the dormant subpopulation at later infection time points, identifying SifA as the first known effector regulating bacterial dormancy in epithelial cells. SifA-induced Salmonella-induced filaments (SIFs) characterize the mature Salmonella-containing vacuole (SCV), and we observed that SIFs were needed for intravacuolar growth of Salmonella. We could show that SIF formation was critical for nutrient acquisition within the SCV; inhibition of SIF formation resulted in a higher proportion of dormant bacteria, akin to the effect of reduced glucose availability during infection. Both bacterial and host glycolysis pathways were required to prevent dormancy, as proper nutrient scavenging through SIF-mediated modification of the SCV is essential for maintaining a replicative, non-dormant state. These results underscore the importance of nutrient access, facilitated by reprogramming host endomembrane trafficking, for Salmonella to avoid dormancy and sustain active replication within its intracellular niche. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/631959v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@d4e9cdorg.highwire.dtl.DTLVardef@419d70org.highwire.dtl.DTLVardef@1c75fb0org.highwire.dtl.DTLVardef@5b5d59_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Bacterial filamentation is an in vivo mechanism for cell-to-cell spreading 94%
- Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes 94%
- Dual RNA-seq provides insight into the biology of the neglected intracellular human pathogen Orientia tsutsugamushi 94%
Similar papers in this journal
- Salmonella endorses a dormant state within human epithelial cells for persistent infection 95%
- Fluorescent secreted bacterial effectors reveal active intravacuolar proliferation of Listeria monocytogenes in epithelial cells 95%
- The type 3 secretion system requires actin polymerization to open translocon pores 94%
Similar papers in this journal
- A new class of protein sensor links spirochete pleomorphism, persistence, and chemotaxis 93%
- A new role for lipoproteins LpqZ and FecB in orchestrating mycobacterial cell envelope biogenesis 93%
- Outer membrane tube formation by Francisella novicida involves extensive envelope modifications and is linked with type VI secretion and alterations to the host phagosomal membrane 93%
Similar papers in this journal
- The Achromobacter Type 3 secretion system drives pyroptosis and immunopathology via independent activation of NLRC4 and NLRP3 inflammasomes 95%
- Multi-conflict islands are a widespread trend within Serratia spp 94%
- Differential translocation of bacteriophages across the intestinal barrier in health and Crohn's disease 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.