Salmonellae interplay with host cells

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Abstract
Salmonellae are globally important Gram-negative bacterial pathogens that infect a range of hosts and cause several diseases, including gastroenteritis and typhoid fever. Orally ingested bacteria can survive in the inhospitable environment of the digestive tract and relocate to the intestine, where they invade the intestinal epithelia and either stimulate inflammation and fluid secretion (gastroenteritis) or cross the intestinal barrier and disseminate throughout the reticuloendothelial system (typhoid fever). Salmonellae use two type III secretion systems (T3SSs) to deliver bacterial virulence proteins, called effectors, directly into host cells. The T3SS that is encoded on Salmonella pathogenicity island (SPI)-1 is responsible for delivering effectors across the plasma membrane and is involved in the invasion of epithelial cells and modulation of inflammation responses. The SPI2-encoded T3SS delivers effectors across the vacuolar membrane and contributes to the survival and replication of intracellular salmonellae. Recent findings suggest that the functions of these two T3SSs are not completely separate and might overlap. The activities of several SPI1 T3SS effectors stimulate host actin-cytoskeletal rearrangements by either directly modulating actin dynamics or activating host GTPases, which results in membrane ruffling and bacterial uptake. The activation of host GTPases also triggers cell-signalling cascades, which promotes the production of host inflammatory responses. After bacterial internalization, the host-cell actin cytoskeleton is returned to its normal shape and the inflammatory response is down-modulated. This reversal of actin rearrangement is modulated by SPI1 T3SS effectors, which manipulate the host-cell GTPases and signalling molecules that are involved in inflammation. Intracellular salmonellae resist killing by a range of host innate immune responses and reside in a specialized vacuole, called the Salmonella-containing vacuole (SCV). Sensing of antimicrobial peptides and the low pH of the SCV activates a large number of Salmonella genes that are involved in the remodelling of surface proteins and regulation of virulence genes The intracellular environment induces expression of the SPI2 T3SS, which is responsible for specific intracellular phenotypes, such as the formation of Salmonella-induced filaments, maintenance of the SCV membrane, perinuclear localization of the SCV and manipulation of the microtubule and actin networks around the SCV.