Characterization of differential pore-forming activities of ESAT-6 proteins from Mycobacterium tuberculosis and Mycobacterium smegmatis

  • FEBS Lett. 2016 Feb;590(4):509-19. doi: 10.1002/1873-3468.12072.
Xiuli Peng  1  2 ,  Guozhong Jiang  2 ,  Wei Liu  2 ,  Qi Zhang  2 ,  Wei Qian  3 ,  Jianjun Sun  2  3
Affiliations
  • 1. Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction, Ministry of Education, Huazhong Agriculture University, Wuhan, China.
  • 2. Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.
  • 3. Sino-Duth Biomedical and Information Engineering School of Northeastern University, Shenyang, China.
PMID: 26801203 DOI: 10.1002/1873-3468.12072
Abstract

Mycobacterium tuberculosis ESAT-6 (MtbESAT-6) plays essential roles in pathogenesis. MtbESAT-6 exhibits a unique pore-forming activity (PFA) that is not found in its ortholog from non-pathogenic Mycobacterium smegmatis (MsESAT-6). Here, we characterized the differential PFAs and found that exchange of I25-H26/T25-A26 between two proteins reciprocally affected their PFAs. MtbESAT-6(IH/TA) had ~ 40% reduction, while MsESAT-6(TA/IH) fully acquired its activity similar to MtbESAT-6. Mutations of A17E, K38T, N67L or R74Q on MtbESAT-6(IH/TA) further reduced the activity, with MtbESAT-6(IH/TA-17) being the lowest. This study suggests I25-H26 as the pH-sensor essential for MsESAT-6 to fully acquire the activity, while multiple residues contributed to MtbESAT-6 PFA.

Keywords
ESAT-6; Mycobacterium tuberculosis; pathogenesis; pore-forming activity; virulence factor.
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