Dataset Information

Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

ABSTRACT: Typhoid toxin is an essential virulence factor of Salmonella Typhi, the cause of typhoid fever. Typhoid toxin is secreted into the lumen of Salmonella-containing vacuole (SCV), after which it is packaged into vesicle carrier intermediates and released extracellularly through incompletely understood mechanisms. Following export, the toxin targets cells by interacting with human-specific Neu5Ac-terminated glycan receptors. We show that typhoid toxin is sorted from the SCV into vesicle carrier intermediates via interactions of its B subunit, PltB, with specific lumenal sialylated glycan packaging receptors. Cells deficient in N-glycosylation or the synthesis of specific gangliosides or displaying Neu5Gc-terminated, as opposed to Neu5Ac-terminated, glycans do not support typhoid toxin export. Additionally, typhoid toxin packaging requires the specific SCV environment, as toxin produced by an S. Typhi mutant with impaired trafficking is not properly sorted into vesicles. These results reveal how the exotoxin of an intracellular pathogen engages host pathways for packaging and release.

SUBMITTER: Chang SJ

PROVIDER: S-EPMC5110213 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

Chang Shu-Jung SJ Song Jeongmin J Galán Jorge E JE

Cell host & microbe 20161101 5

Typhoid toxin is an essential virulence factor of Salmonella Typhi, the cause of typhoid fever. Typhoid toxin is secreted into the lumen of Salmonella-containing vacuole (SCV), after which it is packaged into vesicle carrier intermediates and released extracellularly through incompletely understood mechanisms. Following export, the toxin targets cells by interacting with human-specific Neu5Ac-terminated glycan receptors. We show that typhoid toxin is sorted from the SCV into vesicle carrier inte ...[more]

PMID: 27832592

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Project description:The development of multidrug resistance in Salmonella enterica serovar Typhi currently forms a major roadblock for the treatment of enteric fever. This poses a major health problem in endemic regions and extends to travellers returning from developing countries. The appearance of fluoroquinolone non-susceptible strains has resulted in use of ceftriaxone as drug of choice with azithromycin being recommended for uncomplicated cases of typhoid fever. A recent sporadic instance of decreased susceptibility to the latest drug regime has necessitated a detailed analysis of antimicrobial resistance genes and possible relationships with their phenotypes to facilitate selection of future treatment regimes. Whole genome sequencing (WGS) was conducted for 133 clinical isolates from typhoid patients. Sequence output files were processed for pan-genome analysis and prediction of antimicrobial resistance genes. The WGS analyses disclosed the existence of fluoroquinolone resistance conferring mutations in gyrA, gyrB, parC and parE genes of all strains. Acquired resistance determining mechanisms observed included catA1 genes for chloramphenicol resistance, dfrA7, dfrA15, sul1 and sul2 for trimethoprim-sulfamethoxazole and blaTEM-116/blaTEM-1B genes for amoxicillin. No resistance determinants were found for ceftriaxone and cefixime. The genotypes were further correlated with their respective phenotypes for chloramphenicol, ampicillin, co-trimoxazole, ciprofloxacin and ceftriaxone. A high correlation was observed between genotypes and phenotypes in isolates of S. Typhi. The pan-genome analysis revealed that core genes were enriched in metabolic functions and accessory genes were majorly implicated in pathogenesis and antimicrobial resistance. The pan-genome of S. Typhi appears to be closed (Bpan??=??0.09) as analysed by Heap's law. Simpson's diversity index of 0.51 showed a lower level of genetic diversity among isolates of S. Typhi. Overall, this study augments the present knowledge that WGS can help predict resistance genotypes and eventual correlation with phenotypes, enabling the chance to spot AMR determinants for fast diagnosis and prioritize antibiotic use directly from sequence.

Dataset Information

Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

Publications

Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

Similar Datasets

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