Anti-chlamydial activities of cell-permeable hydrophobic dipeptide-containing derivatives.

The obligate intracellular bacteria chlamydia is major human pathogen that causes millions of trachoma, sexually transmitted infections and pneumonia worldwide. We serendipitously found that both calpain inhibitors z-Val-Phe-CHO and z-Leu-Nle-CHO showed marked inhibitory activity against chlamydial growth in human epithelial HeLa cells, whereas other calpain inhibitors not. These peptidomimetic inhibitors consist of N-benzyloxycarbonyl group and hydrophobic dipeptide derivatives. Both compounds strongly restrict the chlamydial growth even addition at the 12 h post infection. Notably, inhibitors-mediated growth inhibition of chlamydia was independent on host calpain activity. Electron microscopic analysis revealed that z-Val-Phe-CHO inhibited chlamydial growth by arresting bacterial cell division and RB-EB re-transition, but not by changing into persistent state. We searched and found that z-Leu-Leu-CHO and z-Phe-Ala-FMK also inhibited chlamydial growth. Neither biotin-hydrophobic dipeptide nor morpholinoureidyl-hydrophobic dipeptide shows inhibitory effects on chlamydial intracellular growth. Our results suggested the possibility of some chemical derivatives based on z-hydrophobic dipeptide group for future therapeutic usage to the chlamydial infectious disease.

Chlamydia trachomatis impairs host base excision repair by downregulating polymerase ß.

Chlamydia trachomatis infections have been associated with ovarian cancer by several epidemiological studies. Here, we show that C. trachomatis-infected primary human ovarian epithelial cells display elevated oxidative DNA damage. Base excision repair, an important cellular mechanism to repair oxidative DNA lesions, was impaired in infected primary ovarian and in several other types of cells. Polymerase ß was downregulated in infected cells associated with upregulation of microRNA-499a (miR-499a). Stabilising polymerase ß by inhibiting miR-499a significantly improved repair. Moreover, downregulation of tumour suppressor p53 also resulted in attenuated repair in these cells. Thus, our data show that downregulation of polymerase ß by direct inhibition through miR-499a and downregulation of p53 debilitate the host-cell base excision repair during C. trachomatis infection.

Chlamydia trachomatis uses host cell dynein to traffic to the microtubule-organizing center in a p50 dynamitin-independent process.

Chlamydiae are pathogenic obligate intracellular bacteria with a biphasic developmental cycle that involves cell types adapted for extracellular survival (elementary bodies, EBs) and intracellular multiplication (reticulate bodies, RBs). The intracellular development of chlamydiae occurs entirely within a membrane-bound vacuole termed an inclusion. Within 2 hours after entry into host cells, Chlamydia trachomatis EBs are trafficked to the perinuclear region of the host cell and remain in close proximity to the Golgi apparatus, where they begin to fuse with a subset of host vesicles containing sphingomyelin. Here, we provide evidence that chlamydial migration from the cell periphery to the peri-Golgi region resembles host cell vesicular trafficking. Chlamydiae move towards the minus end of microtubules and aggregate at the microtubule-organizing center (MTOC). In mammalian cells the most important minus-end-directed microtubule motor is cytoplasmic dynein. Microinjection of antibodies to a subunit of cytoplasmic dynein inhibited movement of chlamydiae to the MTOC, whereas microinjection of antibodies to the plus-directed microtubule motor, kinesin, had no effect. Surprisingly, overexpression of the protein p50 dynamitin, a subunit of the dynactin complex that links vesicular cargo to the dynein motor in minus directed vesicle trafficking, did not abrogate chlamydial migration even though host vesicle transport was inhibited. Nascent chlamydial inclusions did, however, colocalize with the p150(Glued) dynactin subunit, which suggests that p150(Glued) may be required for dynein activation or processivity but that the cargo-binding activity of dynactin, supplied by p50 dynamitin subunits and possibly other subunits, is not. Because chlamydial transcription and translation were required for this intracellular trafficking, chlamydial proteins modifying the cytoplasmic face of the inclusion membrane are probable candidates for proteins fulfilling this function.

Complicaciones nasofaríngeas de la conjutivitis folicular por chalmydia trachomatis. Una causa de la falta de respuesta al tratamiento / Nasopharingeal complications secundary to Clamydia trachomatis follicular conjunctivitis. A cause of therapeutic failure

Se realizó un estudio retrospectivo en 6 409 casos consecutivos en un lapso de enero de 1992 a febrero de 1997, se seleccionaron 183 frotis nasales y 271 faríngeos provenientes de 396 pacientes. Chlamydia trachomatis fue el agente etiológico en el 67.80 por ciento de los frotis nasales y 8.11 por ciento de las muestras faríngeas. La infección nasal es casi siempre secundaria a la infección ocular y a su vez es un factor de diseminación y de falta de respuesta adecuada al tratamiento, por lo que es indispensable identificar el problema y dar tratamiento simultáneo

Seroprevalencia de infección por Chlamydia pneumoniae en población sana de Santiago de Chile / Seroprevalence of chlamydia pneumoniae infection in healthy population from Santiago, Chile

La evidencia de exposición previa a Chlamydia pneumoniae fue evaluada en 353 sujetos sanos de Santiago de Chile. Se efectuó determinación sérica de anticuerpos (IgG) específicos anti-Chlamydia pneumoniae con antígenos de la cepa AR-39 proporcionados por la Washington Research Foundation, con técnica de inmunofluorescencia indirecta. Títulos iguales o mayores de 1:16 fueron considerados positivos. 134 sueros fueron positivos para Chlamydia penumoniae, con título máximo de 1:256. Concluimos que en esta muestra la seroprevalencia fue de 38 por ciento y que en un título igual o mayor de 1:512 sugiere el diagnóstico de infección aguda por Chlamydia pneumoniae