Bloodstream Infections.

is a major foodborne pathogen of both animals and humans. This bacterium is responsible for considerable morbidity and mortality world-wide. Different serovars of this genus cause diseases ranging from self-limiting gastroenteritis to a potentially fatal systemic disease known as enteric fever.

Immune evasion and persistence in enteric bacterial pathogens.

The major function of the mammalian immune system is to prevent and control infections caused by enteropathogens that collectively have altered human destiny. In fact, as the gastrointestinal tissues are the major interface of mammals with the environment, up to 70% of the human immune system is dedicated to patrolling them The defenses are multi-tiered and include the endogenous microflora that mediate colonization resistance as well as physical barriers intended to compartmentalize infections. The gastrointestinal tract and associated lymphoid tissue are also protected by sophisticated interleaved arrays of active innate and adaptive immune defenses.

The Salmonella type III effector SpvC triggers the reverse transmigration of infected cells into the bloodstream.

Salmonella can appear in the bloodstream within CD18 expressing phagocytes following oral ingestion in as little as 15 minutes. Here, we provide evidence that the process underlying this phenomenon is reverse transmigration. Reverse transmigration is a normal host process in which dendritic cells can reenter the bloodstream by traversing endothelium in the basal to apical direction.

Human Genome-Wide RNAi Screen for Host Factors That Facilitate Salmonella Invasion Reveals a Role for Potassium Secretion in Promoting Internalization.

Salmonella enterica can actively invade the gastro-intestinal epithelium. This frequently leads to diarrheal disease, and also gives the pathogen access to phagocytes that can serve as vehicles for dissemination into deeper tissue. The ability to invade host cells is also important in maintaining the carrier state.

A naturally occurring single nucleotide polymorphism in the Salmonella SPI-2 type III effector srfH/sseI controls early extraintestinal dissemination.

CD18 expressing phagocytes associated with the gastro-intestinal (GI) epithelium can shuttle Salmonella directly into the bloodstream within a few minutes following microbial ingestion. We have previously demonstrated that Salmonella controls the CD18 pathway to deeper tissue, manipulating the migratory properties of infected cells as an unappreciated component of its pathogenesis. We have observed that one type III effector, SrfH (also called SseI) that Salmonella secretes into infected phagocytes manipulates the host protein TRIP6 to stimulate their migration.

Human genome-wide RNAi screen for host factors that modulate intracellular Salmonella growth.

Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. While much has been learned about the microbial genes that influence the infectious process through decades of intensive research, relatively little is known about the host factors that affect infection. We performed a genome-wide siRNA screen to identify host genes that Salmonella enterica serovar Typhimurium (S.

An anomalous type IV secretion system in Rickettsia is evolutionarily conserved.

Background: Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.

Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells.

The mammalian host has a number of innate immune mechanisms designed to limit the spread of infection, yet many bacteria, including Salmonella, can cause systemic disease. Salmonella typhimurium-infected phagocytes traverse the gastrointestinal (GI) epithelium and enter the bloodstream within minutes after ingestion, thereby spreading throughout its host. Here, we provide a cellular and molecular basis for this phenomenon.