Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model

Mamoudou Maiga, Nisheeth Agarwal, Nicole Ammerman, Radhika Gupta, Haidan Guo, Marama C. Maiga, Shichun Lun, William Ramses Bishai

Research output: Contribution to journalArticle

Abstract

Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans.

Original languageEnglish (US)
Article numbere30749
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 3 2012

Fingerprint

Phosphodiesterase Inhibitors
tuberculosis
shortenings
adjuvants
Tuberculosis
animal models
therapeutics
Pharmaceutical Preparations
Chemotherapy
Pathology
Therapeutics
Tissue
drugs
duration
drug resistance
United States Food and Drug Administration
Drug Resistance
infectious diseases
drug therapy
Communicable Diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model. / Maiga, Mamoudou; Agarwal, Nisheeth; Ammerman, Nicole; Gupta, Radhika; Guo, Haidan; Maiga, Marama C.; Lun, Shichun; Bishai, William Ramses.

In: PLoS One, Vol. 7, No. 2, e30749, 03.02.2012.

Research output: Contribution to journalArticle

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