Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

Xiu Zhen Fan, Jimin Xu, Megan Files, Jeffrey D. Cirillo, Janice Endsley, Jia Zhou, Mark Endsley

Research output: Contribution to journalArticle

Abstract

The human immunodeficiency virus (HIV)pandemic is driving the re-emergence of tuberculosis (TB)as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/anti-mycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.

Original languageEnglish (US)
JournalTuberculosis
DOIs
StatePublished - Jan 1 2019

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Niclosamide
Mycobacterium tuberculosis
HIV-1
HIV
Macrophages
Multidrug-Resistant Tuberculosis
Jurkat Cells
Pandemics
Virus Replication
Coinfection
Drug Resistance
Pharmaceutical Preparations
Antiviral Agents
Tuberculosis
Beijing
Anti-Bacterial Agents
Viruses
T-Lymphocytes
Growth
Infection

Keywords

  • Co-infection
  • Drug development
  • HIV
  • Niclosamide
  • Tuberculosis

ASJC Scopus subject areas

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

Cite this

Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing). / Fan, Xiu Zhen; Xu, Jimin; Files, Megan; Cirillo, Jeffrey D.; Endsley, Janice; Zhou, Jia; Endsley, Mark.

In: Tuberculosis, 01.01.2019.

Research output: Contribution to journalArticle

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