RESUMO
Compared to cervical cancer, little is known about human papillomavirus (HPV)-driven oropharyngeal cancer and their cofactors. Here, we investigated potential associations between Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) with oral HPV and HPV persistence, which are known cofactors in cervical carcinogenesis, and also play a role in HPV-driven oropharyngeal cancer. Saliva samples (n = 547) from 312 people were tested for CT and NG and whom had previously been tested for oral HPV infection in a longitudinal study. Eight participants were positive for CT (2.6%) and one for NG (0.3%). Six of these nine participants were also positive for oral HPV in at least one of their samples. We found no significant associations between HPV, CT, or NG infection in the saliva samples analyzed. These preliminary data suggest CT and NG have little influence on oral HPV-positivity and persistence in a general population. However, larger studies focusing on 'at risk' population cohorts are necessary to assess potential associations between oral sexually transmissible infections and oral HPV infections, and their outcomes.
Assuntos
Coinfecção , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Neisseria gonorrhoeae , Chlamydia trachomatis , Coinfecção/epidemiologia , Estudos Longitudinais , Papillomavirus HumanoAssuntos
Proteínas de Bactérias , DNA Girase , Farmacorresistência Bacteriana , Infecções por Mycoplasma , Mycoplasma genitalium , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Austrália/epidemiologia , Fluoroquinolonas/farmacologia , Macrolídeos , Mutação , Mycoplasma genitalium/genética , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Queensland , DNA Girase/genética , DNA Girase/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
Antibiotics are failing fast, and the development pipeline remains alarmingly dry. New drug research and development is being urged by world health officials, with new antibacterials against multidrug-resistant Gram-negative pathogens as the highest priority. Antivirulence drugs, which inhibit bacterial pathogenicity factors, are a class of promising antibacterials, however, their development is stifled by lack of standardised preclinical testing akin to what guides antibiotic development. The lack of established target-specific microbiological assays amenable to high-throughput, often means that cell-based testing of virulence inhibitors is absent from the discovery (hit-to-lead) phase, only to be employed at later-stages of lead optimization. Here, we address this by establishing a pipeline of bacterial cell-based assays developed for the identification and early preclinical evaluation of DsbA inhibitors, previously identified by biophysical and biochemical assays. Inhibitors of DsbA block oxidative protein folding required for virulence factor folding in pathogens. Here we use existing Escherichia coli DsbA inhibitors and uropathogenic E. coli (UPEC) as a model pathogen, to demonstrate that the combination of a cell-based sulfotransferase assay and a motility assay (both DsbA reporter assays), modified for a higher throughput format, can provide a robust and target-specific platform for the identification and evaluation of DsbA inhibitors.