Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.

The aim of this study was to evaluate the impact of carbapenem-resistant K. pneumoniae bloodstream infections on mortality. During the study period 42, 68 and 120 patients were identified with carbapenem-resistant, extended-spectrum β-lactamase producers (ESBL) and susceptible K. pneumoniae bloodstream infections, respectively. Patients with carbapenem-resistant K. pneumoniae had higher rates of prior antimicrobial exposure, other nosocomial infections, and use of invasive devices. Infection-related mortality was 48% for carbapenem-resistant, 22% for ESBL producers and 17% for susceptible K. pneumoniae. Independent risk factors for infection-related mortality were Pitt bacteraemia score, Charlson score and carbapenem resistance.

Of all known Salmonella enterica serovars, S. Infantis is one of the most commonly isolated and has been recently emerging worldwide. To understand the recent emergence of S. Infantis in Israel, we performed extensive comparative analyses between pre-emergent and the clonal emergent S. Infantis populations. We demonstrate the fixation of adaptive mutations in the DNA gyrase (gyrA) and nitroreductase (nfsA) genes, conferring resistance to quinolones and nitrofurans, respectively, and the carriage of an emergent-specific plasmid, designated pESI. This self-transferred episome is a mosaic megaplasmid (∼280 kb), which increases bacterial tolerance to environmental mercury (mer operon) and oxidative stress, and provides further resistance to tetracycline, sulfamethoxazole and trimethoprim, most likely due to the presence of tetRA, sulI and dfrA genes respectively. Moreover, pESI carries the yersiniabactin siderophore system and two novel chaperone-usher fimbriae. In vitro studies established that pESI conjugation into a plasmidless S. Infantis strain results in superior biofilm formation, adhesion and invasion into avian and mammalian host cells. In vivo mouse infections demonstrated higher pathogenicity and increased intestinal inflammation caused by an S. Infantis strain harboring pESI compared with the plasmidless parental strain. Our results indicate that the presence of pESI that was found only in the emergent population of S. Infantis in Israel contributes significantly to antimicrobials tolerance and pathogenicity of its carrier. It is highly likely that pESI plays a key role in the successful spread of the emergent clone that replaced the local S. Infantis community in the short time of only 2-3 years.

SummaryPathogenicity islands (PAIs) are distinct genetic elements on the chromosomes of a large number of bacterial pathogens. PAIs encode various virulence factors and are normally absent from non-pathogenic strains of the same or closely related species. PAIs are considered to be a subclass of genomic islands that are acquired by horizontal gene transfer via transduction, conjugation and transformation, and provide 'quantum leaps' in microbial evolution. Data based on numerous sequenced bacterial genomes demonstrate that PAIs are present in a wide range of both Gram-positive and Gram-negative bacterial pathogens of humans, animals and plants. Recent research focused on PAIs has not only led to the identification of many novel virulence factors used by these species during infection of their respective hosts, but also dramatically changed our way of thinking about the evolution of bacterial virulence.