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Salmonella Paratyphi A (SPtA) remains one of the leading causes of enteric (typhoid) fever. Yet, despite the recent increased rate of isolation from patients in Asia, our understanding of its pathogenesis is incomplete. Here we investigated inflammasome activation in human macrophages infected with SPtA. We found that SPtA induces GSDMD‐mediated pyroptosis via activation of caspase‐1, caspase‐4 and caspase‐8. Although we observed no cell death in the absence of a functional Salmonella pathogenicity island‐1 (SPI‐1) injectisome, HilA‐mediated overexpression of the SPI‐1 regulon enhances pyroptosis. SPtA expresses FepE, an LPS O‐antigen length regulator, which induces the production of very long O‐antigen chains. Using a ΔfepE mutant we established that the very long O‐antigen chains interfere with bacterial interactions with epithelial cells and impair inflammasome‐mediated macrophage cell death. Salmonella Typhimurium (STm) serovar has a lower FepE expression than SPtA, and triggers higher pyroptosis, conversely, increasing FepE expression in STm reduced pyroptosis. These results suggest that differential expression of FepE results in serovar‐specific inflammasome modulation, which mirrors the pro‐ and anti‐inflammatory strategies employed by STm and SPtA, respectively. Our studies point towards distinct mechanisms of virulence of SPtA, whereby it attenuates inflammasome‐mediated detection through the elaboration of very long LPS O‐polysaccharides. [ABSTRACT FROM AUTHOR]

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems. [ABSTRACT FROM AUTHOR]

Shigellosis is the major global cause of dysentery. Shigella sonnei, which has historically been more commonly isolated in developed countries, is undergoing an unprecedented expansion across industrializing regions in Asia, Latin America, and the Middle East. The precise reasons underpinning the epidemiological distribution of the various Shigella species and this global surge in S. sonnei are unclear but may be due to three major environmental pressures. First, natural passive immunization with the bacterium Plesiomonas shigelloides is hypothesized to protect populations with poor water supplies against S. sonnei. Improving the quality of drinking water supplies would, therefore, result in a reduction in P. shigelloides exposure and a subsequent reduction in environmental immunization against S. sonnei. Secondly, the ubiquitous amoeba species Acanthamoeba castellanii has been shown to phagocytize S. sonnei efficiently and symbiotically, thus allowing the bacteria access to a protected niche in which to withstand chlorination and other harsh environmental conditions in temperate countries. Finally, S. sonnei has emerged from Europe and begun to spread globally only relatively recently. A strong selective pressure from localized antimicrobial use additionally appears to have had a dramatic impact on the evolution of the S. sonnei population. We hypothesize that S. sonnei, which exhibits an exceptional ability to acquire antimicrobial resistance genes from commensal and pathogenic bacteria, has a competitive advantage over S. flexneri, particularly in areas with poorly regulated antimicrobial use. Continuing improvement in the quality of global drinking water supplies alongside the rapid development of antimicrobial resistance predicts the burden and international distribution of S. sonnei will only continue to grow. An effective vaccine against S. sonnei is overdue and may become one of our only weapons against this increasingly dominant and problematic gastrointestinal pathogen. [ABSTRACT FROM AUTHOR]

For microbial pathogens, phylogeographic differentiation seems to be relatively common. However, the neutral population structure of Salmonella enterica serovar Typhi reflects the continued existence of ubiquitous haplotypes over millennia. In contrast, clinical use of fluoroquinolones has yielded at least 15 independent gyrA mutations within a decade and stimulated clonal expansion of haplotype H58 in Asia and Africa. Yet, antibiotic-sensitive strains and haplotypes other than H58 still persist despite selection for antibiotic resistance. Neutral evolution in Typhi appears to reflect the asymptomatic carrier state, and adaptive evolution depends on the rapid transmission of phenotypic changes through acute infections. [ABSTRACT FROM AUTHOR]

Shigella flexneri serotype 6 is an understudied cause of diarrhoeal diseases in developing countries, and has been proposed as one of the major targets for vaccine development against shigellosis. Despite being named as S. flexneri , Shigella flexneri serotype 6 is phylogenetically distinct from other S. flexneri serotypes and more closely related to S. boydii . This unique phylogenetic relationship and its low sampling frequency have hampered genomic research on this pathogen. Herein, by utilizing whole genome sequencing (WGS) and analyses of Shigella flexneri serotype 6 collected from epidemiological studies (1987-2013) in four Asian countries, we revealed its population structure and evolutionary history in the region. Phylogenetic analyses supported the delineation of Asian Shigella flexneri serotype 6 into two phylogenetic groups (PG-1 and -2). Notably, temporal phylogenetic approaches showed that extant Asian S. flexneri serotype 6 could be traced back to an inferred common ancestor arising in the 18 th century. The dominant lineage PG-1 likely emerged in the 1970s, which coincided with the times to most recent common ancestors (tMRCAs) inferred from other major Southeast Asian S. flexneri serotypes. Similar to other S. flexneri serotypes in the same period in Asia, genomic analyses showed that resistance to first-generation antimicrobials was widespread, while resistance to more recent first-line antimicrobials was rare. These data also showed a number of gene inactivation and gene loss events, particularly on genes related to metabolism and synthesis of cellular appendages, emphasizing the continuing role of reductive evolution in the adaptation of the pathogen to an intracellular lifestyle. Together, our findings reveal insights into the genomic evolution of the understudied Shigella flexneri serotype 6, providing a new piece in the puzzle of Shigella epidemiology and evolution.

Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease worldwide, disproportionately affecting young children in developing countries and high-risk communities in developed settings. Antimicrobial treatment, most commonly with fluoroquinolones, is currently recommended for Shigella infections to alleviate symptoms and control disease transmission. Resistance to fluoroquinolones has emerged in differing Shigella species (S. dysenteriae, flexneri and sonnei) since the turn of the 21st century, originating in endemic areas, and latterly spreading into non-endemic regions. Despite occurring independently, the emergence of fluoroquinolone resistance in these different Shigella species shares striking similarities regarding their epidemiology and resistance mechanisms. Here, we review and discuss the current epidemiology of fluoroquinolone-resistant Shigella species, particularly in the light of recent genomic insights.

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.