Project description:Multidrug-resistant Shigella sonnei in Spain: an ever-evolving problem?
| PRJEB51813 | ENA
Project description:Circulation of multidrug-resistant Shigella sonnei and Shigella flexneri among men who have sex with men in Barcelona, Spain, 2015-2019
Project description:"Shigella spp. are the causative agents of shigellosis, which remains a major cause of death in children under the age of five. Shigellosis is marked by fever and leads to hemorrhagic diarrhea; Shigella bacteremia are reported in more severe cases. These clinical features strongly suggest that Shigella survive to plasma exposure, although it has not been previously investigated at a molecular level. In this report, we confirmed in a guinea pig model of shigellosis that local hemorrhages were induced by S. flexneri 5a and S. sonnei and we demonstrated that Shigella reached CD31+/CD34+ blood vessels within the mucosa during late infection stage and further disseminated in the blood circulation. These results confirmed the exposition of Shigella to plasma components during its virulence cycle, from the hemorrhagic colonic mucosa to the blood circulation. We demonstrated that all tested Shigella strains survived to plasma exposure in vitro and we have shown that Serine Protease Autrotransporters of Enterobacteriaceae (SPATEs) are essential for Shigella dissemination within the colonic mucosa and in the blood circulation. We confirmed that SPATEs were expressed and secreted within poorly oxygenated environments encountered by Shigella from hypoxic foci of infection to the blood circulation. We have further demonstrated that SPATEs promoted the survival of Shigella to plasma exposure, by cleaving the complement 3 component (C3), hence impairing the complement system activation."
Project description:Background Compelling evidence indicates that Shigella species, the etiologic agents of bacillary dysentery, as well as enteroinvasive Escherichia coli, are derived from multiple origins of Escherichia coli and form a single pathovar. To further understand the genome diversity and virulence evolution of Shigella, comparative genomic hybridization microarray analysis was employed to compare the gene content of E. coli K-12 with those of 43 Shigella strains from all serotypes. Results For the 43 strains subjected to CGH microarray analyses, the common backbone of the Shigella genome was estimated to contain more than 1,900 open reading frames, with a mean number of 729 undetectable ORFs. The mosaic distribution of absent regions indicated that insertions and/or deletions have led to the highly diversified genomes of pathogenic strains. Conclusion These results support the hypothesis that by gain and loss of functions, Shigella species became successful human pathogens through convergent evolution from diverse genomic backgrounds. Moreover, we also found many specific differences between different lineages, providing a window into understanding bacterial speciation and taxonomic relationships. Keywords: comparative genomic hybridization
Project description:In Australia, cases of shigellosis usually occur in returned travelers from regions of shigellosis endemicity or in men who have sex with men. Resistance to multiple antibiotics has significantly increased in Shigella sonnei isolates and represents a significant public health concern. We investigate an outbreak of multidrug-resistant S. sonnei in Victoria, Australia. We undertook whole-genome sequencing of 54 extended-spectrum-beta-lactamase (ESBL)-producing S. sonnei isolates received at the Microbiological Diagnostic Unit Public Health Laboratory between January 2019 and March 2020. The population structure and antimicrobial resistance profiles were identified by genomic analyses, with 73 previously characterized Australian S. sonnei isolates providing context. Epidemiological data, including age and sex of the shigellosis cases, were also collected. There was a significant increase in cases of ESBL S. sonnei from July 2019. Most of the ESBL S. sonnei isolates (65%) fell within a single cluster that was predominantly comprised of male cases that were characterized by the presence of the blaCTX-M-27 gene conferring resistance to extended-spectrum cephalosporins. These isolates were also multidrug resistant, including resistance to azithromycin and co-trimoxazole and reduced susceptibility to ciprofloxacin. Our data uncovered a prolonged clonal outbreak of ESBL S. sonnei infection that was likely first introduced by returned travelers and has subsequently been circulating locally in Australia. The emergence of a local outbreak of ESBL S. sonnei with a multidrug-resistant profile, including reduced susceptibility to ciprofloxacin, represents a significant public health threat.
Project description:to analyse the transcriptomic response of human intestinal tissue engrafted in SCID mice to Shigella infection Keywords: infection, Shigella, gene expression, intestinal cell
2008-06-23 | GSE8636 | GEO
Project description:Emergence of multidrug-resistant Shigella sonnei and Shigella flexneri among men who have sex with men: Spain, 2020-2021