In vitro model of mycobacteria and HIV-1 co-infection for drug discovery

Sudhamathi Vijayakumar, Sarah Finney John, Rebecca J. Nusbaum, Monique Ferguson, Jeffrey D. Cirillo, Omonike Olaleye, Janice Endsley

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Tuberculosis (TB) has become a global health threat in the wake of the Human Immunodeficiency Virus (HIV) pandemic and is the leading cause of death in people with HIV/AIDS. Treatment of patients with Mycobacterium tuberculosis (Mtb)/HIV co-infection is complicated by drug interactions and toxicity that present huge challenges for clinical intervention. Discovery efforts to identify novel compounds with increased effectiveness and decreased drug-drug interactions against Mtb, HIV-1, or both, would be greatly aided by the use of a co-infection model for screening drug libraries. Currently, inhibitors of Mtb are screened independently in mycobacterial cell cultures or target based biochemical screens and less often in macrophages or peripheral blood leukocytes. Similarly, HIV-1 drugs are screened in vitro independently from anti-mycobacterial compounds. Here, we describe an in vitro model where primary human peripheral blood mononuclear cells or monocyte-derived macrophages are infected with Mycobacterium bovis BCG and HIV-1, and used to evaluate drug toxicity and activity in a co-infection setting. Our results with standard compounds (e.g. Azidothymidine, Rifampicin) demonstrate the utility of this in vitro model to evaluate drug effectiveness relevant to cellular toxicity, HIV-1 replication, and intracellular mycobacterial growth, through the use of ELISA, bacterial enumeration, and multi-variate flow cytometry. This model and associated assays have great value in accelerating the discovery of compounds for use in Mtb/HIV-1 co-infected patients.

Original languageEnglish (US)
JournalTuberculosis
Volume93
Issue numberSUPPL.
DOIs
StatePublished - Dec 1 2013

Fingerprint

Drug Discovery
Mycobacterium
Coinfection
HIV-1
Mycobacterium tuberculosis
HIV
Mycobacterium bovis
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
Macrophages
Pharmaceutical Preparations
Preclinical Drug Evaluations
Zidovudine
Pandemics
Virus Diseases
Rifampin
Virus Replication
Libraries
Cause of Death
Blood Cells

Keywords

  • Drug screening/Drug interactions
  • HIV
  • In vitro model
  • TB

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

In vitro model of mycobacteria and HIV-1 co-infection for drug discovery. / Vijayakumar, Sudhamathi; John, Sarah Finney; Nusbaum, Rebecca J.; Ferguson, Monique; Cirillo, Jeffrey D.; Olaleye, Omonike; Endsley, Janice.

In: Tuberculosis, Vol. 93, No. SUPPL., 01.12.2013.

Research output: Contribution to journalArticle

Vijayakumar, Sudhamathi ; John, Sarah Finney ; Nusbaum, Rebecca J. ; Ferguson, Monique ; Cirillo, Jeffrey D. ; Olaleye, Omonike ; Endsley, Janice. / In vitro model of mycobacteria and HIV-1 co-infection for drug discovery. In: Tuberculosis. 2013 ; Vol. 93, No. SUPPL.
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