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Bladder infection affects a hundred million people annually, but our understanding of bladder immunity is incomplete. We found type 17 immune response genes among the most up-regulated networks in mouse bladder following uropathogenic Escherichia coli (UPEC) challenge. Intravital imaging revealed submucosal Rorc+ cells responsive to UPEC challenge, and we found increased Il17 and IL22 transcripts in wild-type and Rag2 -/- mice, implicating group 3 innate lymphoid cells (ILC3s) as a source of these cytokines. NCR-positive and negative ILC3 subsets were identified in murine and human bladders, with local proliferation increasing IL17-producing ILC3s post infection. ILC3s made a more limited contribution to bladder IL22, with prominent early induction of IL22 evident in Th17 cells. Single-cell RNA sequencing revealed bladder NCR-negative ILC3s as the source of IL17 and identified putative ILC3-myeloid cell interactions, including via lymphotoxin-β-LTBR. Altogether, our data provide important insights into the orchestration and execution of type 17 immunity in bladder defense.

Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population., Author Summary Salmonella enterica is a diverse species, isolates of which can colonise or infect many different animals, including humans and can cause different disease syndromes. S. enterica can be sub-typed using serology into serovars. Isolates from some serovars, known as generalists, can infect multiple hosts (e.g. S. Typhimurium) and usually cause gastroenteritis. However, other serovars exhibit host adaptation or even restriction. Host-adapted serovars such as S. Dublin show preference for a particular host but can also infect other hosts, while host-restricted serovars are capable of infecting only a single host (e.g. S. Typhi in humans) and frequently cause febrile systemic disease (typhoid). In this study, we use genotypic and phenotypic methods to investigate clinical isolates representative of populations of two recently emerged S. Typhimurium lineages of type ST313 associated with invasive disease in sub-Saharan Africa. Our results identify potential characteristics in these isolates that may be associated with adaptation to invasive disease in humans with a compromised immunity.

Nature Communications 5: Article number:4544 (2014); Published 4 Aug 2014; Updated 28 Jan 2015 The original version of this Article contained an error in the spelling of a member of the DEVANI Consortium, Lucilla Baldassarri, which was incorrectly given as Lucilia Baldassari. This has now been corrected in both the PDF and HTML versions of the Article.

All strains of group A Streptococcus (GAS), a leading cause of infection-related mortality worldwide, express group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N...

A Salmonella typhimurium strain harboring stable mutations in both ompC and ompF was constructed from the mouse-virulent strain S. typhimurium SL1344. When administered orally to BALB/c mice the strain was attenuated, with the 50% lethal dose (LD50) reduced by approximately 1,000-fold. However, the intravenous LD50 was reduced only by approximately 10-fold. The ompC ompF mutant persisted in murine tissues for several weeks following oral challenge, and mice immunized with this mutant were well protected against challenge with virulent SL1344. A strain harboring a stable mutation in tppB behaved in a manner similar to that of strain SL1344 in vivo, while a strain harboring mutations in ompC, ompF, and tppB behaved as an ompC ompF mutant in vivo, indicating that the tppB operon is not required for virulence in S. typhimurium.

Results: Addition of a soluble cocktail containing six protease inhibitors to a culture abolished the ability of B. pseudomallei to grow on ferritin as sole iron source. Addition of individual proteases contained in the cocktail revealed that two of them, AEBSF (4-[2-aminoethyl] benzene sulfonyl fluoride) and EDTA exhibited the most potent effect. These data are consistent with the previous finding that B. cenocepacia employs a serine protease for ferritin iron acquisition. Mutants that had all seven serine proteases individually deleted were successfully constructed. All mutants were still able to utilize ferritin as sole iron source at rates indistinguishable from the parent strain. The most plausible explanation for this observation is that B. pseudomallei does not employ a serine protease for ferritin iron acquisition. Conclusion: We have provided conclusive evidence that ferritin-iron acquisition by B. pseudomallei involves proteolytic degradation of ferritin but the protease(s) and other factors, e.g. transporters, involved in this process remain tobe identified.Defining a ferritin-iron acquisition pathway will substantially alter our current view of iron acquisition mechanisms in Gram-negative bacteria and provide a more complete picture of the pathogenesis of infection with B. pseudomallei.

One hundred fifty Tn5 IS50L::phoA (TnphoA) mutants of a mouse-virulent, nalidixic acid-resistant (Nalr), prototrophic Salmonella typhimurium strain, C5 Nalr, were isolated. None of the mutants were auxotrophs. Groups of 8 to 10 BALB/c mice were infected orally with each of 95 mutants with a dose equivalent to 20-fold the 50% lethal dose of the wild-type C5 Nalr strain, and deaths were counted over the next 28 days. Fifteen of the mutants failed to kill any mice, whereas all mice died following challenge with the other mutants. Nine of the 15 attenuated mutants exhibited a defect in lipopolysaccharide biosynthesis. The remaining six mutants were smooth. The TnphoA transposon of each of the smooth attenuated mutants was moved, using P22-mediated transduction, into a fresh C5 background, and all retransductants were still attenuated. Analysis of the membrane proteins of the attenuated mutants failed to reveal any alterations in detectable major outer membrane proteins, although colonies of two of the mutants exhibited a mucoid phenotype following growth on L-agar plates. Individual attenuated mutants differed in their abilities to translocate to livers and spleens of mice following oral infection. All of the smooth TnphoA mutants exhibited increased 50% lethal doses with respect to the wild type following intravenous infection of BALB/c mice. Southern analysis of DNA prepared from each of the mutants suggested that TnphoA had inserted into a number of different sites in the S. typhimurium genome. None of the TnphoA mutants had inserts in the virulence-associated plasmid.