Secreted acid phosphatase (SapM) of Mycobacterium tuberculosis is indispensable for arresting phagosomal maturation and growth of the pathogen in guinea pig tissues.

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  • Author(s): Puri RV;Puri RV; Reddy PV; Tyagi AK
  • Source:
    PloS one [PLoS One] 2013 Jul 26; Vol. 8 (7), pp. e70514. Date of Electronic Publication: 2013 Jul 26 (Print Publication: 2013).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Acid Phosphatase/*metabolism ; Guinea Pigs/*microbiology ; Mycobacterium tuberculosis/*enzymology ; Phagosomes/*microbiology ; Tuberculosis/*microbiology; Acid Phosphatase/genetics ; Animals ; Cell Line ; Gene Deletion ; Humans ; Macrophages/microbiology ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/growth & development ; Tuberculosis/enzymology ; Tuberculosis/veterinary
    • Abstract:
      Tuberculosis (TB) is responsible for nearly 1.4 million deaths globally every year and continues to remain a serious threat to human health. The problem is further complicated by the growing incidence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), emphasizing the need for the development of new drugs against this disease. Phagosomal maturation arrest is an important strategy employed by Mycobacterium tuberculosis to evade the host immune system. Secretory acid phosphatase (SapM) of M.tuberculosis is known to dephosphorylate phosphotidylinositol 3-phosphate (PI3P) present on phagosomes. However, there have been divergent reports on the involvement of SapM in phagosomal maturation arrest in mycobacteria. This study was aimed at reascertaining the involvement of SapM in phagosomal maturation arrest in M.tuberculosis. Further, for the first time, we have also studied whether SapM is essential for the pathogenesis of M.tuberculosis. By deleting the sapM gene of M.tuberculosis, we demonstrate that MtbΔsapM is defective in the arrest of phagosomal maturation as well as for growth in human THP-1 macrophages. We further show that MtbΔsapM is severely attenuated for growth in the lungs and spleen of guinea pigs and has a significantly reduced ability to cause pathological damage in the host when compared with the parental strain. Also, the guinea pigs infected with MtbΔsapM exhibited a significantly enhanced survival when compared with M.tuberculosis infected animals. The importance of SapM in phagosomal maturation arrest as well as in the pathogenesis of M.tuberculosis establishes it as an attractive target for the development of new therapeutic molecules against tuberculosis.
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    • Accession Number:
      EC 3.1.3.2 (Acid Phosphatase)
    • Publication Date:
      Date Created: 20130808 Date Completed: 20140402 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      PMC3724783
    • Accession Number:
      10.1371/journal.pone.0070514
    • Accession Number:
      23923000