Novel insights into Mycobacterium antigen Ag85 biology and implications in countermeasures for M. tuberculosis.

Tuberculosis remains one of the most prevalent and deadly infectious diseases, largely due to the emergence of multidrug-resistant and extensive drug-resistant Mycobacterium tuberculosis, especially the coinfection with HIV. Mycobacterium Ag85 complex (Ag85A, B, and C), with a carboxylesterase consensus sequence and conserved surface catalysis residues, involves in cell wall biosynthesis and the trigger of the host immune response. The physiological function, structures, distributions, and molecular mechanisms of regulations as well as their implications in novel vaccines and diagnostics against tuberculosis are summarized. Special focus is the regulation underlying the Ag85 expression. This will facilitate in-depth understanding of the role of Ag85 and developing better novel measures against M. tuberculosis infection.

New insights into the pathogenesis of tuberculosis revealed by Mycobacterium marinum: the zebrafish model from the systems biology perspective.

Tuberculosis remains a worldwide health concern, largely due to the emergence of multi-drug-resistant (MDR) and extensive-drug-resistant (XDR) Mycobacterium tuberculosis co-infection with HIV. The exact mechanism of Mycobacterium virulence, pathogenesis, and persistence is not fully understood. The hallmark of tuberculosis, granulomas are promoted by Mycobacterium virulence factors, and they have long been considered a structural advantage to the host. However, this traditional view has been challenged recently, largely due to the evidence originating from the M. marinum-zebrafish model. As a genetically tractable model, zebrafish provide unprecedented opportunities to address the pathogenesis of tuberculosis from a systems biology perspective. The latest data from this model are summarized in this review, special attention is given to the shared pathway and network between zebrafish and humans. This research serves to deepen our understanding of this complex process and to promote the discovery of better countermeasures against tuberculosis.

Identification of idiosyncratic Mycobacterium tuberculosis ribosomal protein subunits with implications in extraribosomal function, persistence, and drug resistance based on transcriptome data.

Ribosome, the protein synthesis machinery essential for all living cells, consists of ribosomal proteins and RNA. Extraribosomal functions have recently been discovered for many ribosomal proteins, acting either as individual regulatory proteins or as a complex with other cell components. However, extraribosomal functions of Mycobacterium tuberculosis ribosomal proteins have not been systematically addressed. To this end, M. tuberculosis ribosomal proteins potentially engaged in extraribosomal functions were curated by data mining from transcriptional profiles of M. tuberculosis exposed to diverse treatments. Six M. tuberculosis ribosomal proteins, namely, S3 (Rv0707, rpsC), L16 (Rv0708, rplP), L29 (Rv0709, rpmC), S17 (Rv0710, rpsQ), S14 (Rv2056c, rpsN2), and L33 (Rv2057c, rpmG1), were found to behave idiosyncratically. The function of these abnormal ribosomal subunits can be further explored. Special emphasis is on their potential value as novel targets for better antibiotics.