Abstract
Tuberculosis (TB), a leading infectious disease caused by Mycobacterium tuberculosis strain, takes four human lives every minute globally. Paucity of knowledge on M. tuberculosis virulence and antibiotic resistance is the major challenge for tuberculosis control. We have identified 47 acetyltransferases in the M. tuberculosis, which use diverse substrates including antibiotic, amino acids, and other chemical molecules. Through comparative analysis of the protein file of the virulent M. tuberculosis H37Rv strain and the avirulent M. tuberculosis H37Ra strain, we identified one acetyltransferase that shows significant variations with N-terminal deletion, possibly influencing its physicochemical properties. We also found that one acetyltransferase has three types of post-translation modifications (lysine acetylation, succinylation, and glutarylation). The genome context analysis showed that many acetyltransferases with their neighboring genes belong to one operon. By data mining from published transcriptional profiles of M. tuberculosis exposed to diverse treatments, we revealed that several acetyltransferases may be functional during M. tuberculosis infection. Insights obtained from the present study can potentially provide clues for developing novel TB therapeutic interventions.
Highlights
TB remains a major threat for global health largely due to vast mortality and morbidity
We found that one acetyltransferase can be lysine acetylated, succinylated and glutarylated, and many acetyltransferases with their neighboring genes are conserved in mycobacteria
Possible, probable, or hypothetical proteins were searched in the proteome of M. tuberculosis H37Rv, and a total of 47 acetyltransferases was found (Supplementary Table S1)
Summary
TB remains a major threat for global health largely due to vast mortality and morbidity. The increase of incidences with MDR TB (multidrug resistant TB) and XDR TB (extensively drug-resistant TB) further exacerbates the difficulty of TB patients’ treatment. It is imperative to find new targets and new anti-TB drugs. Rv0262c, a conserved aminoglycoside 2 -N-acetyltransferase (AAC(2 )-Ic) in mycobacteria, can acetylate all known aminoglycosides including ribostamycin, neomycin B, gentamicin, and tobramycin bearing 2 amino group [2,3]. Rv3225c, a putative phophotransferase containing GNAT (GCN5-related acetyltransferase) domain in N terminus, was found to have low level of aminoglycoside-modifying activity conferring resistance to aminoglycoside antibiotic in mycobacteria [5]. Eis (rv2416c, enhanced intracellular survival gene), one lysine N-acetyltransferase, was found its overexpression conferring M. tuberculosis kanamycin resistance [6]. About 80% of clinical isolates harboring eis promoter mutations exhibited
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