Mycobacterial biofilms as players in human infections: a review.

The role of biofilms in pathogenicity and treatment strategies is often neglected in mycobacterial infections. In recent years, the emergence of nontuberculous mycobacterial infections has necessitated the development of novel prophylactic strategies and elucidation of the mechanisms underlying the establishment of chronic infections. More importantly, the question arises whether members of the Mycobacterium tuberculosis complex can form biofilms and contribute to latent tuberculosis and drug resistance because of the long-lasting and recalcitrant nature of its infections. This review discusses some of the molecular mechanisms by which biofilms could play a role in infection or pathological events in humans.

Antimycobacterial Precatorin A Flavonoid Displays Antibiofilm Activity against Mycobacterium bovis BCG.

The aim of this study was to evaluate the potential antibiofilm activity of Rhynchosia precatoria (R. precatoria) compounds over Mycobacterium bovis BCG (M. bovis BCG) as a model for Mycobacterium tuberculosis (Mtb). We evaluated the antibiofilm activity as the ability to both inhibit biofilm formation and disrupt preformed biofilms (bactericidal) of R. precatoria compounds, which have been previously described as being antimycobacterials against Mtb. M. bovis BCG developed air-liquid interface biofilms with surface attachment ability and drug tolerance. Of the R. precatoria extracts and compounds that were tested, precatorin A (PreA) displayed the best biofilm inhibitory activity, as evaluated by biofilm biomass quantification, viable cell count, and confocal and atomic force microscopy procedures. Furthermore, its combination with isoniazid at subinhibitory concentrations inhibited M. bovis BCG biofilm formation. Nonetheless, neither PreA nor the extract showed bactericidal effects. PreA is the R. precatoria compound responsible for biofilm inhibitory activity against M. bovis BCG.

Identification of immunogenic T-cell peptides of Mycobacterium tuberculosis PE_PGRS33 protein.

The development of a more efficient vaccine is needed to improve tuberculosis control. One of the current approaches is to identify immunogenic T-cell peptides that can elicit a protective and specific immune response. These peptides come from immunogenic proteins of the pathogen. The PE_PGRS33 protein of Mycobacterium tuberculosis has been proved immunogenic. However, little is known about immunogenic T-cell peptides of PE_PGRS33 and their interactions with MHC-II molecules. Therefore, we used the SYFPHEITHI database to determine the immunogenic PE_PGRS33 T-cell peptides. Next, we built homology models by using MOE v2018.1 software in order to obtain information about the specific interactions between the peptides and I-Ak. The AlgPred server was employed to look for allergenic sites in PE_PGRS33. We developed a sequence alignment between PE_PGRS33 and all the human proteins by using BLAST. Three peptides were commercially synthesized, and their activity was evaluated in vitro by the stimulation of PBMC from household contacts of TB patients. Our in silico results showed five immunogenic T-cell peptides. BLAST analysis showed low homology of PE_PGRS33 with human proteins and AlgPred did not reveal allergenic sites in PE_PGRS33. The three peptides triggered the activation of CD4+ T cells from the households contacts, showed by the production of IFN-γ. We identified three immunogenic peptides of PE_PGRS33 that demonstrated activity in vitro which allows to deepen into the immune response towards mycobacterial antigens, moving forward to the identification of new vaccine candidates.