Helicobacter pylori-derived neutrophil-activating protein increases the lifespan of monocytes and neutrophils.

An invariable feature of Helicobacter pylori-infected gastric mucosa is the persistent infiltration of inflammatory cells. The neutrophil-activating protein (HP-NAP) has a pivotal role in triggering and orchestrating the phlogistic process associated with H. pylori infection. Aim of this study was to address whether HP-NAP might further contribute to the inflammation by increasing the lifespan of inflammatory cells. We report that HP-NAP is able to prolong the lifespan of monocytes, in parallel with the induction of the anti-apoptotic proteins A1, Mcl-1, Bcl-2 and Bcl-X(L). This effect does not result from a direct action on the apoptotic machinery, but rather it requires the release of endogenous pro-survival factors, such as interleukin-1beta, which probably acts in synergy with other unidentified mediators. We also report that HP-NAP promotes the survival of Ficoll-purified neutrophils in a monocyte-dependent fashion: indeed, mononuclear cell depletion of Ficoll-purified neutrophils completely abolished the pro-survival effect by HP-NAP. In conclusion, our data reinforce the notion that HP-NAP has a pivotal role in sustaining a prolonged activation of myeloid cells.

被引量：8 发表：1970

A novel Phytophthora infestans haustorium-specific membrane protein is required for infection of potato.

Phytophthora infestans causes late-blight, a devastating and re-emerging disease of potato crops. During the early stages of infection, P. infestans differentiates infection-specific structures such as appressoria for host epidermal cell penetration, followed by infection vesicles, and haustoria to establish a biotrophic phase of interaction. Here we report the cloning, from a suppression subtractive hybridization library, of a P. infestans gene called Pihmp1 encoding a putative glycosylated protein with four closely spaced trans-membrane helices. Pihmp1 expression is upregulated in germinating cysts and in germinating cysts with appressoria, and significantly upregulated throughout infection of potato. Transient gene silencing of Pihmp1 led to loss of pathogenicity and indicated involvement of this gene in the penetration and early infection processes of P. infestans. P. infestans transformants expressing a Pihmp1::monomeric red fluorescent protein (mRFP) fusion demonstrated that Pihmp1 was translated in germinating sporangia, germinating cysts and appressoria, accumulated in the appressorium, and was located at the haustorial membrane during infection. Furthermore, we discovered that haustorial structures are formed over a 3 h period, maturing for up to 12 h, and that their formation is initiated only at sites on the surface of intercellular hyphae where Pihmp1::mRFP is localized. We propose that Pihmp1 is an integral membrane protein that provides physical stability to the plasma membrane of P. infestans infection structures. We have provided the first evidence that the surface of oomycete haustoria possess proteins specific to these biotrophic structures, and that formation of biotrophic structures (infection vesicles and haustoria) is essential to successful host colonization by P. infestans.

被引量：43 发表：1970

Acute oral toxicity of Yersinia pseudotuberculosis to fleas: implications for the evolution of vector-borne transmission of plague.

Yersinia pestis diverged from Yersinia pseudotuberculosis</= 20 000 years ago, during which time it evolved to be transmitted by fleas. In comparing the ability of these closely related species to infect the rat flea Xenopsylla cheopis, we found that Y. pseudotuberculosis, unlike Y. pestis, is orally toxic to fleas. Fleas showed signs of acute toxicity, including diarrhoea, immediately after feeding on blood containing Y. pseudotuberculosis in response to protein toxin(s) produced by the bacteria. Adherence of Y. pseudotuberculosis to the midgut and large intracellular vacuoles in midgut epithelial cells were detected during the first 24 h after infection. The insect pathogen Photorhabdus luminescens and its TcdA1 and TcdB1-TccC1 insecticidal toxin complexes were similarly toxic to fleas, implicating the toxin complex (tc) genes also present in Yersinia species. However, the Y. pestis and Y. pseudotuberculosis TcaAB and TcaC-TccC proteins were non-toxic to fleas, and Y. pseudotuberculosis mutants deleted of tc genes retained acute toxicity. Our results indicate that loss of one or more insect gut toxins was a critical step in the recent evolution of flea-borne transmission in the genus Yersinia. Changes in the tc insecticidal genes do not appear to have been responsible, but may have had other effects on Yersinia-flea interactions.

被引量：31 发表：1970

Do type 1 fimbriae promote inflammation in the human urinary tract?

Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.

被引量：26 发表：1970

The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm.

被引量：141 发表：2005