Expression of phospholipase D, the major virulence factor of Corynebacterium pseudotuberculosis, is regulated by multiple environmental factors and plays a role in macrophage death

McKean, Sandra C; Davies, John K.; Moore, Robert J.

doi:10.1099/mic.0.2007/005926-0

Cited by 69 publications

(54 citation statements)

References 27 publications

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“…The transposon insertion sites for these mutants were determined to be located within the following loci by inverse PCR: disulfide bond formation protein (A1S_3365), putative general secretion pathway protein (A1S_0269), hydrolase isochorimatase family protein (A1S_3278), a putative promoter region of exoribonuclease R (A1S_3045; two mutants), and a putative phospholipase D (A1S_2989). While it is difficult to predict a priori how many of these factors affect the organism's ability to proliferate in serum, phospholipase D is a well-characterized virulence factor that has been suggested to play an important role in hematogenous dissemination of other bacterial pathogens within infected animals (23).…”

Section: Resultsmentioning

confidence: 99%

Inactivation of Phospholipase D Diminishes Acinetobacter baumannii Pathogenesis

Hood²,

et al. 2010

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Acinetobacter baumannii is an emerging bacterial pathogen of considerable health care concern. Nonetheless, relatively little is known about the organism's virulence factors or their regulatory networks. Septicemia and ventilator-associated pneumonia are two of the more severe forms of A. baumannii disease. To identify virulence factors that may contribute to these disease processes, genetically diverse A. baumannii clinical isolates were evaluated for the ability to proliferate in human serum. A transposon mutant library was created in a strain background that propagated well in serum and screened for members with decreased serum growth. The results revealed that disruption of A. baumannii phospholipase D (PLD) caused a reduction in the organism's ability to thrive in serum, a deficiency in epithelial cell invasion, and diminished pathogenesis in a murine model of pneumonia. Collectively, these results suggest that PLD is an A. baumannii virulence factor.

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Section: Resultsmentioning

confidence: 99%

Inactivation of Phospholipase D Diminishes Acinetobacter baumannii Pathogenesis

Hood²,

et al. 2010

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“…Phospholipases are known to play important roles in pathogenesis in a wide range of bacterial pathogens (Schmiel and Miller 1999;McDermott et al 2004;McKean et al 2007). C. trachomatis carries three PLD gene clusters, two of which are present in all of the sequenced Chlamydia and Chlamydophila, and the third cluster, found in the PZ, is specific to C. trachomatis and C. muridarum and is phylogenetically distinct from the two other PLD clusters.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates

Thomson

Holden²,

Carder³

et al. 2007

Genome Res.

200

180

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Chlamydia trachomatis is the most common cause of sexually transmitted infections in the UK, a statistic that is also reflected globally. There are three biovariants of C. trachomatis: trachoma (serotypes A–C) and two sexually transmitted pathovars; serotypes D–K and lyphogranuloma venereum (LGV). Trachoma isolates and the sexually transmitted serotypes D–K are noninvasive, whereas the LGV strains are invasive, causing a disseminating infection of the local draining lymph nodes. Genome sequences are available for single isolates from the trachoma (serotype A) and sexually transmitted (serotype D) biotypes. We sequenced two isolates from the remaining biotype, LGV, a long-term laboratory passaged strain and the recent “epidemic” LGV isolate-causing proctitis. Although the genome of the LGV strain shows no additional genes that could account for the differences in disease outcome, we found evidence of functional gene loss and identified regions of heightened sequence variation that have previously been shown to be important sites for interstrain recombination. We have used new sequencing technologies to show that the recent clinical LGV isolate causing proctitis is unlikely to be a newly emerged strain but is most probably an old strain with relatively new clinical manifestations.

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“…Currently, mammalian PLDs are recognized as key enzymes in intracellular signaling involved in processes such as inflammation, endocytosis, and cell shape changes (27), while bacterial PLDs from Corynebacterium pseudotuberculosis and Acinetobacter baumannii have been shown to be the critical virulence determinants of these organisms (25,29,44). In fungi, PLD appears to be closely related to fungal cell shape changes, such as sporulation in Saccharomyces cerevisiae (55) and the dimorphic transition of C. albicans (14).…”

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confidence: 99%

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

Gao

Han

et al. 2012

Infect Immun

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Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 M phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.

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Expression of phospholipase D, the major virulence factor of Corynebacterium pseudotuberculosis, is regulated by multiple environmental factors and plays a role in macrophage death

Cited by 69 publications

References 27 publications

Inactivation of Phospholipase D Diminishes Acinetobacter baumannii Pathogenesis

Inactivation of Phospholipase D Diminishes Acinetobacter baumannii Pathogenesis

Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

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