Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580

Canals, Rocı́o; Hammarlöf, Disa L.; Kröger, Carsten; Owen, Siân V.; Fong, Wai Yee; Lacharme-Lora, Lizeth; Zhu, Xiaojun; Wenner, Nicolas; Carden, Sarah; Honeycutt, Jared; Monack, Denise M.; Kingsley, Robert A.; Brownridge, Philip; Chaudhuri, Roy R.; Rowe, Will; Predeus, Alexander V.; Hokamp, Karsten; Gordon, Michael A.; Hinton, Jay C. D.

doi:10.1371/journal.pbio.3000059

Cited by 71 publications

(171 citation statements)

References 90 publications

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“…A comparison of the coding sequences (CDS) of the enzymes involved in the riboflavin biosynthesis pathway found only one nucleotide change (SNP) between the sequence type 19 STM-4/74 and the sequence type 313 STM-D23580 strains. This synonymous coding variant was located in the ribD gene (Glu316Glu) [43], suggesting that there were no biochemical differences between the riboflavin biosynthesis pathways of the sequence type 313 and sequence type 19 isolates.…”

Section: Resultsmentioning

confidence: 99%

“…Data represented in panels B and C were extracted from Canals et.al. [43]. (D) PBMC were infected at two different MOI (2 and 5) with STM-D23580 (blue), STM-4/74 (green) or STM-4/74 RibB ++ (pink).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…To determine whether the enzymes of the riboflavin pathway of the sequence type 19 STM-4/74 and sequence type 313 STM-D23580 strains were expressed at different levels, we investigated the transcriptomic and proteomic data from our recent comparative analysis [43]. Strains STM-4/74 and STM-D23580 are closely-related, sharing 92% of coding genes [43]. Differential gene expression analysis of the rib genes at the transcriptomic level identified significant up-regulation of ribB (≥2 fold-change, FDR ≤0.001) in STM-D23580 in four out of the five experimental conditions (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

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AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB

Preciado-Llanes

Aulicino

Canals

et al. 2019

Preprint

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SUMMARYMucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defence. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with a selective absence of MAIT cells have not been identified. We report that typhoidal and non-typhoidal S. enterica strains generally activate MAIT cells. However, African invasive disease-associated multidrug-resistant S. Typhimurium sequence type 313 lineage 2 strains escape MAIT cell recognition through overexpression of ribB, a bacterial gene that encodes the 4-dihydroxy-2-butanone 4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. This MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of S. Typhimurium sequence type 313 lineage 2 in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB

Preciado-Llanes

Aulicino

Canals

et al. 2019

Preprint

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“…The S. Typhimurium serovar causes two-thirds of iNTS in sub-Saharan Africa, and phylogenetic analysis has revealed that the bacteria represent a distinct pathovariant that is multidrug resistant and belongs to a specific multi-locus sequence type, S. Typhimurium Sequence Type 313 (ST313) [Kingsley et al, 2009;Okoro et al, 2012;Canals et al, 2019;Van Puyvelde et al, 2019]. Recent studies have addressed the abilities of the ST313 bacteria to disseminate systemically, as well as their capacity to survive intracellularly in various experimental models, including macrophages [Herrero-Fresno et al, 2014;Carden et al, 2015;Ramachandran et al, 2015;Singletary et al, 2016;Lacharme-Lora et al, 2019].…”

Section: Introductionmentioning

confidence: 99%

Increased intracellular survival of Salmonella Typhimurium ST313 in HIV‐1‐infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment

Lê-Bury

Deschamps

Kizilyaprak

et al. 2020

Biology of the Cell

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Background Non‐typhoidal Salmonella (NTS) causes a severe invasive syndrome (iNTS disease) described in HIV‐positive adults. The impact of HIV‐1 on Salmonella pathogenesis and the molecular basis for the differences between these bacteria and classical diarrhoeal S. Typhimurium remains unclear. Results Here, we show that iNTS‐associated S. Typhimurium Sequence Type 313 (ST313) bacteria show greater intracellular survival in primary human macrophages, compared with a ‘classical’ diarrhoeal S. Typhimurium ST19 isolate. The increased intracellular survival phenotype of ST313 is more pronounced in HIV‐infected macrophages. We explored the possibility that the bacteria take advantage of the HIV‐associated viral‐containing compartments created in human macrophages that have low pH. Confocal fluorescence microscopy and focussed ion beam‐scanning electron microscopy tomography showed that Salmonella did not co‐localise extensively with HIV‐positive compartments. Conclusion The capacity of ST313 bacteria to survive better than ST19 bacteria within primary human macrophages is enhanced in cells pre‐infected with HIV‐1. Our results indicate that the ST313 bacteria do not directly benefit from the niche created by the virus in HIV‐1‐infected macrophages, and that they might take advantage from a more globally modified host cell. Significance A better understanding of the interplay between HIV‐1 and Salmonella is important not only for these bacteria but also for other opportunistic pathogens.

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Targeting Two-Component Systems Uncovers a Small-Molecule Inhibitor of Salmonella Virulence

Tsai

MacNair

Cao

et al. 2020

Cell Chemical Biology

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Salmonella serovars are leading causes of gastrointestinal disease and have become increasingly resistant to fluoroquinolone and cephalosporin antibiotics. Overcoming this healthcare crisis requires new approaches in antibiotic discovery and the identification of unique bacterial targets. In this work, we describe a chemical genomics approach to identify inhibitors of Salmonella virulence. From a cell-based, promoter reporter screen of $50,000 small molecules, we identified dephostatin as a non-antibiotic compound that inhibits intracellular virulence factors and polymyxin resistance genes. Dephostatin disrupts signaling through both the SsrA-SsrB and PmrB-PmrA two-component regulatory systems and restores sensitivity to the lastresort antibiotic, colistin. Cell-based experiments and mouse models of infection demonstrate that dephostatin attenuates Salmonella virulence in vitro and in vivo, suggesting that perturbing regulatory networks is a promising strategy for the development of anti-infectives. ll Article

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Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580

Cited by 71 publications

References 90 publications

AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB

AfricanSalmonellaTyphimurium sequence type 313 lineage 2 evades MAIT cell recognition by overexpressing RibB

Increased intracellular survival of Salmonella Typhimurium ST313 in HIV‐1‐infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment

Targeting Two-Component Systems Uncovers a Small-Molecule Inhibitor of Salmonella Virulence

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