The Salmonella enterica PhoP Directly Activates the Horizontally Acquired SPI-2 Gene sseL and Is Functionally Different from a S. bongori Ortholog

To establish a successful infection within the host, a pathogen must closely regulate multiple virulence traits to ensure their accurate temporal and spatial expression. As a highly adapted intracellular pathogen, Salmonella enterica has acquired during its evolution various virulence genes via numerous lateral transfer events, including the acquisition of the Salmonella Pathogenicity Island 2 (SPI-2) and its associated effectors. Beneficial use of horizontally acquired genes requires that their expression is effectively coordinated with the already existing virulence programs and the regulatory set-up in the bacterium. As an example for such a mechanism, we show here that the ancestral PhoPQ system of Salmonella enterica is able to regulate directly the SPI-2 effector gene sseL (encoding a secreted deubiquitinase) in an SsrB-independent manner and that PhoP plays a part in a feed-forward regulatory loop, which fine-tunes the cellular level of SseL. Additionally, we demonstrate the presence of conserved cis regulatory elements in the promoter region of sseL and show direct binding of purified PhoP to this region. Interestingly, in contrast to the S. enterica PhoP, an ortholog regulator from a S. bongori SARC 12 strain was found to be impaired in promoting transcription of sseL and other genes from the PhoP regulon. These findings have led to the identification of a previously uncharacterized residue in the DNA-binding domain of PhoP, which is required for the transcriptional activation of PhoP regulated genes in Salmonella spp. Collectively our data demonstrate an interesting interface between the acquired SsrB regulon and the ancestral PhoPQ regulatory circuit, provide novel insights into the function of PhoP, and highlight a mechanism of regulatory integration of horizontally acquired genes into the virulence network of Salmonella enterica

Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization

Author summary The intestinal epithelium is a crucial biological interface, interacting with both commensal and pathogenic microorganisms. It’s lined with heavily glycosylated proteins and glycolipids which can act as both attachment sites and energy sources for intestinal bacteria. Fut2, the enzyme governing epithelial α1,2-fucosylation, has been implicated in the interaction between microbes and intestinal epithelial cells. Salmonella is one of the most important bacterial gastrointestinal pathogens affecting millions of people worldwide. Salmonella possesses fimbrial and non-fimbrial adhesins which can be used to adhere to host cells. Here we show that Salmonella expresses Std fimbriae in the gastrointestinal tract in vivo and exploit Std fimbriae to bind fucosylated structures in the mucus and on the intestinal epithelium. Furthermore, we demonstrate that the Std fimbriae-fucose interaction is necessary for bacterial colonization of the intestine and for triggering intestinal inflammation. These data lend new insights into bacterial adhesion-epithelial interactions which are essential for bacterial pathogenesis and key factors in determining tissue tropism and host susceptibility to infectious disease

Differentiate to thrive: lessons from the Legionella pneumophila life cycle

When confronted by disparate environments, microbes routinely alter their physiology to tolerate or exploit local conditions. But some circumstances require more drastic remodelling of the bacterial cell, as sporulation by the Bacillus and Streptomyces species of soil bacteria vividly illustrates. Cellular differentiation is also crucial for pathogens, the challenge for which is to colonize one host, then be transmitted to the next. Using the Gram-negative Legionella pneumophila as a model intracellular pathogen, we describe how biogenesis of the replication vacuole is determined by the developmental state of the bacterium. Subsequently, when replicating bacteria have exhausted the nutrient supply, the pathogens couple their conversion to stationary phase physiology with expression of traits that promote transmission to a new host. The cellular differentiation of L. pneumophila is co-ordinated by a regulatory circuit that integrates several elements that are broadly conserved in the microbial world. The alarmone (p)ppGpp promotes transcription directed by the alternative sigma factors RpoS, FliA and, probably, RpoN, and also post-transcriptional control mediated by a two-component regulatory system, LetA/S (GacA/S), and an mRNA-binding protein, CsrA (RsmA). By applying knowledge of microbial differentiation in combination with tools to screen the complete genomes of pathogens, experiments can be designed to identify two distinct classes of virulence traits: factors that promote replication and those dedicated to transmission.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72854/1/j.1365-2958.2004.04129.x.pd

A Health eLearning Ontology and Procedural Reasoning Approach for Developing Personalized Courses to Teach Patients about Their Medical Condition and Treatment

We propose a methodological framework to support the development of personalized courses that improve patients’ understanding of their condition and prescribed treatment. Inspired by Intelligent Tutoring Systems (ITSs), the framework uses an eLearning ontology to express domain and learner models and to create a course. We combine the ontology with a procedural reasoning approach and precompiled plans to operationalize a design across disease conditions. The resulting courses generated by the framework are personalized across four patient axes—condition and treatment, comprehension level, learning style based on the VARK (Visual, Aural, Read/write, Kinesthetic) presentation model, and the level of understanding of specific course content according to Bloom’s taxonomy. Customizing educational materials along these learning axes stimulates and sustains patients’ attention when learning about their conditions or treatment options. Our proposed framework creates a personalized course that prepares patients for their meetings with specialists and educates them about their prescribed treatment. We posit that the improvement in patients’ understanding of prescribed care will result in better outcomes and we validate that the constructs of our framework are appropriate for representing content and deriving personalized courses for two use cases: anticoagulation treatment of an atrial fibrillation patient and lower back pain management to treat a lumbar degenerative disc condition. We conduct a mostly qualitative study supported by a quantitative questionnaire to investigate the acceptability of the framework among the target patient population and medical practitioners

Salmonella Phage ST64B Encodes a Member of the SseK/NleB Effector Family

Salmonella enterica is a species of bacteria that is a major cause of enteritis across the globe, while certain serovars cause typhoid, a more serious disease associated with a significant mortality rate. Type III secreted effectors are major contributors to the pathogenesis of Salmonella infections. Genes encoding effectors are acquired via horizontal gene transfer, and a subset are encoded within active phage lysogens. Because the acquisition of effectors is in flux, the complement of effectors possessed by various Salmonella strains frequently differs. By comparing the genome sequences of S. enterica serovar Typhimurium strain SL1344 with LT2, we identified a gene with significant similarity to SseK/NleB type III secreted effector proteins within a phage ST64B lysogen that is absent from LT2. We have named this gene sseK3. SseK3 was co-regulated with the SPI-2 type III secretion system in vitro and inside host cells, and was also injected into infected host cells. While no role for SseK3 in virulence could be identified, a role for the other family members in murine typhoid was found. SseK3 and other phage-encoded effectors were found to have a significant but sparse distribution in the available Salmonella genome sequences, indicating the potential for more uncharacterised effectors to be present in less studied serovars. These phage-encoded effectors may be principle subjects of contemporary selective processes shaping Salmonella-host interactions

Multidrug-Resistant Salmonella enterica Serovar Infantis, Israel

To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed-field gel electrophoresis profile and a common antimicrobial drug resistance pattern

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities

Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug–resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities