Inhibition of Chlamydiae by Primary Alcohols Correlates with the Strain-Specific Complement of Plasticity Zone Phospholipase D Genes

Nelson, David E.; Crane, Deborah D.; Taylor, Lacey D.; Dorward, David W.; Goheen, Morgan M.; Caldwell, Harlan D.

doi:10.1128/iai.74.1.73-80.2006

Cited by 44 publications

(46 citation statements)

References 35 publications

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“…However, the C. trachomatis genome is predicted to encode one putative lysophospholipase and six phospholipase D (PLD)-like lipases (30). Although these PLDs have been postulated to hydrolyze PC, their substrate specificity in vivo is unknown (31). An alternative means of processing neutral lipids in LDs may be provided by the organelle itself, which comes prepacked with TAG lipases like ATGL, whose activity is normally repressed by ADRP (15).…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole

Cocchiaro

Kumar

Fischer³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

269

328

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The acquisition of host-derived lipids is essential for the pathogenesis of the obligate intracellular bacteria Chlamydia trachomatis. Current models of chlamydial lipid acquisition center on the fusion of Golgi-derived exocytic vesicles and endosomal multivesicular bodies with the bacteria-containing parasitophorous vacuole (''inclusion''). In this study, we describe a mechanism of lipid acquisition and organelle subversion by C. trachomatis. We show by live cell fluorescence microscopy and electron microscopy that lipid droplets (LDs), neutral lipid storage organelles, are translocated from the host cytoplasm into the inclusion lumen. LDs dock at the surface of the inclusion, penetrate the inclusion membrane and intimately associate with reticulate Bodies, the replicative form of Chlamydia. The inclusion membrane protein IncA, but not other inclusion membrane proteins, cofractionated with LDs and accumulated in the inclusion lumen. Therefore, we postulate that the translocation of LDs may occur at IncA-enriched subdomains of the inclusion membrane. Finally, the chlamydial protein Lda3 may participate in the cooption of these organelles by linking cytoplasmic LDs to inclusion membranes and promoting the removal of the LD protective coat protein, adipocyte differentiation related protein (ADRP). The wholesale transport of LDs into the lumen of a parasitophorous vacuole represents a unique mechanism of organelle sequestration and subversion by a bacterial pathogen.ADRP ͉ inclusion ͉ Lda3 ͉ organelle translocation

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Section: Discussionmentioning

confidence: 99%

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole

Cocchiaro

Kumar

Fischer³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

269

328

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“…However, there are two other non-PZ-located PLDs in strain L2: CTL0339 and CTL0536 located in locus 1 and 3, respectively ( Fig. 1; Nelson et al 2006; this study). The PLDs from locus 1 and 3 are Thomson et al…”

Section: The Plasticity Zone (Pz)mentioning

confidence: 99%

“…The PZ PLDs are known to be unique to C. trachomatis and the related rodent pathogen, C. muridarum (Nelson et al 2006). However, there are two other non-PZ-located PLDs in strain L2: CTL0339 and CTL0536 located in locus 1 and 3, respectively ( Fig.…”

Section: The Plasticity Zone (Pz)mentioning

confidence: 99%

Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates

Thomson

Holden²,

Carder³

et al. 2007

Genome Res.

197

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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“…Therefore, the determinants of the different types of infection (invasive or noninvasive) and tissue tropism (eyes, genitals, and lymph nodes) must rely on the few genes present in some strains but not in others and on nucleotide differences which may lead either to proteins with disease group-specific amino acids or to differential gene expression. Some of these determinants were suggested in previous studies: the tryptophan (trpRBA) operon (10,19,51) and genes encoding cytotoxin (11), phospholipase (40), polymorphic membrane proteins (Pmps) (24), and Tarp (34).…”

mentioning

confidence: 99%

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

et al. 2012

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Chlamydia trachomatis is a human bacterial pathogen that multiplies only within an intracellular membrane-bound vacuole, the inclusion. C. trachomatis includes ocular and urogenital strains, usually causing infections restricted to epithelial cells of the conjunctiva and genital mucosa, respectively, and lymphogranuloma venereum (LGV) strains, which can infect macrophages and spread into lymph nodes. However, C. trachomatis genomes display >98% identity at the DNA level. In this work, we studied whether C. trachomatis Inc proteins, which have a bilobed hydrophobic domain that may mediate their insertion in the inclusion membrane, could be a factor determining these different types of infection and tropisms. Analyses of polymorphisms and phylogeny of 48 Inc proteins from 51 strains encompassing the three disease groups showed significant amino acid differences that were mainly due to variations between Inc proteins from LGV and ocular or urogenital isolates. Studies of the evolutionary dynamics of inc genes suggested that 10 of them are likely under positive selection and indicated that most nonsilent mutations are LGV specific. Additionally, real-time quantitative PCR analyses in prototype and clinical strains covering the three disease groups identified three inc genes with LGV-specific expression. We determined the transcriptional start sites of these genes and found LGV-specific nucleotides within their promoters. Thus, subtle variations in the amino acids of a subset of Inc proteins and in the expression of inc genes may contribute to the unique tropism and invasiveness of C. trachomatis LGV strains.

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Inhibition of Chlamydiae by Primary Alcohols Correlates with the Strain-Specific Complement of Plasticity Zone Phospholipase D Genes

Abstract: Members of the genus

Cited by 44 publications

References 35 publications

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole

Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

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