RESUMO
The clinically important Mycobacterium tuberculosis (M. tb) and related mycobacterial pathogens use various virulence mechanisms to survive and cause disease in their hosts. Several well-established virulence factors include the surface-exposed lipids in the mycobacterial outer membrane, as well as the Esx family proteins and the Pro-Glu (PE)/ Pro-Pro-Glu (PPE) family proteins secreted by type VII secretion systems (T7SS). Five ESX T7SS exist in M. tb and three-EsxA secretion system-1 (ESX-1), ESX-3, and ESX-5-have been implicated in virulence, yet only the structures of ESX-3 and ESX-5 have been solved to date. Here, we summarize the current research on three outer membrane lipids-phthiocerol dimycocerosates, phenolic glycolipids, and sulfolipids-as well as the secretion machinery and substrates of three mycobacterial T7SS-ESX-1, ESX-3, and ESX-5. We propose a structural model of the M. tb ESX-1 system based on the latest structural findings of the ESX-3 and ESX-5 secretion apparatuses to gain insight into the transport mechanism of ESX-associated virulence factors.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Lipídeos/química , Mycobacterium tuberculosis/metabolismo , Fatores de Virulência/metabolismo , Animais , Glicolipídeos/química , Humanos , Fenol/química , Propriedades de Superfície , Células THP-1 , VirulênciaRESUMO
Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.