The rhs genes are a family of enigmatic composite genes, widespread among Gram-negative bacteria. In this study, we characterized rhsT, a Pseudomonas aeruginosa rhs gene that encodes a toxic protein. Expression of rhsT was induced upon contact with phagocytic cells. The RhsT protein was exposed on the bacterial surface and translocated into phagocytic cells; these cells subsequently underwent inflammasome-mediated death. Moreover, RhsT enhanced host secretion of the potent proinflammatory cytokines IL-1β and IL-18 in an inflammasome-dependent manner. In a mouse model of acute pneumonia, infection with a P. aeruginosa strain lacking rhsT was associated with less IL-18 production, fewer recruited leukocytes, reduced pulmonary bacterial load, and enhanced animal survival. Thus, rhsT encodes a virulence determinant that activates the inflammasome.rhs element | YD repeat | pathogenesis T he rhs genes are a widely distributed, enigmatic family of horizontally acquired genes. First described in Escherichia coli in the 1980s (1), rhs genes have subsequently been found in a broad range of Gram-negative bacteria, including other members of the Enterobacteriaceae, such as Salmonella, Yersinia, and Photorhabdus, as well as the Pseudomonadaceae, Flavobacteriaceae, Neisseriaceae, Myxoccaceae, and Vibrionaceae. An observed chromosomal rearrangement following recombination between distinct rhs genes in E. coli led to the name "rearrangement hot spot (rhs)" (1). However, recombination events are no longer thought to be a biologically relevant aspect of rhs genes (2). Despite their ubiquity and the many years since their discovery, rhs genes have not been assigned a definitive function, and even clear evidence of gene expression has been elusive (3).Interest in rhs genes has been fueled by their unique structure. These genes, which generally range from 2 to 12 kb in size, exhibit a bipartite structure consisting of two distinct sequences: a long core followed by a short tip (Fig. S1A). Core sequences are GC-rich and display a high degree of intra-and interspecies sequence conservation. In contrast, tip sequences are relatively GC-poor and are highly variable even between closely related rhs genes. Corresponding to the rhs gene core and tip sequences, the proteins predicted to be encoded by rhs genes also contain two regions: a large core domain and a short C-terminal tip domain. Rhs core domains are defined by a variable number of tyrosineaspartate (YD) repeats and are separated from their cognate tip domains by a 61-amino acid hyperconserved region ending in the consensus sequence PXXXXDPXGL (2). Some predicted Rhs proteins also contain a large N-terminal domain. Putative Rhs proteins are predicted to be hydrophilic, and the products of some rhs genes have features of bacteriocins or capsule transport proteins (4-6). Furthermore, Rhs protein YD-repeats and hyperconserved regions display sequence similarity with toxins produced by bacteria that infect insects (7). These observations suggest that some rhs genes encode surface expo...
Mutation of the gene drop-dead (drd) causes adult Drosophila to die within 2 weeks of eclosion and is associated with reduced rates of defecation and increased volumes of crop contents. In the current study, we demonstrate that flies carrying the strong allele drdlwf display a reduction in the transfer of ingested food from the crop to the midgut, as measured both as a change in the steady-state distribution of food within the gut and also in the rates of crop emptying and midgut filling following a single meal. Mutant flies have abnormal triglyceride (TG) and glycogen stores over the first four days post-eclosion, consistent with their inability to move food into the midgut for digestion and nutrient absorption. However, the lifespan of mutants was dependent upon food presence and quality, suggesting that at least some individual flies were able to digest some food. Finally, spontaneous motility of the crop was abnormal in drdlwf flies, with the crops of mutant flies contracting significantly more rapidly than those of heterozygous controls. We therefore hypothesize that mutation of drd causes a structural or regulatory defect that inhibits the entry of food into the midgut.
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