Methamphetamine Enhances Cryptococcus neoformans Pulmonary Infection and Dissemination to the Brain

Patel, Dhavan; Desai, Gunjan M.; Frases, Susana; Cordero, Radames J.  B.; DeLeon-Rodriguez, Carlos M.; Eugenin, Eliseo A.; Nosanchuk, Joshua D.; Martinez, Luis R.

doi:10.1128/mbio.00400-13

Methamphetamine Enhances Cryptococcus neoformans Pulmonary Infection and Dissemination to the Brain

Journal Article · Tue Jul 30 00:00:00 EDT 2013 · mBio (Online)

DOI:https://doi.org/10.1128/mbio.00400-13· OSTI ID:1626103

Patel, Dhavan ^[1]; Desai, Gunjan M. ^[2]; Frases, Susana ^[3]; Cordero, Radames J. B. ^[3]; DeLeon-Rodriguez, Carlos M. ^[4]; Eugenin, Eliseo A. ^[5]; Nosanchuk, Joshua D. ^[4]; Martinez, Luis R. ^[6]

Long Island Univ. Post, Brookville, NY (United States); DOE/OSTI
Long Island Univ. Post, Brookville, NY (United States)
Universidade Federal do Rio de Janeiro (Brazil)
Albert Einstein College of Medicine, Bronx, NY (United States)
University of Medicine and Dentistry of New Jersey, Newark, NJ (United States)
Long Island Univ. Post, Brookville, NY (United States); Albert Einstein College of Medicine, Bronx, NY (United States)

Abstract: Methamphetamine (METH) is a major addictive drug of abuse in the United States and worldwide, and its use is linked to HIV acquisition. The encapsulated fungus Cryptococcus neoformans is the most common cause of fungal meningitis in patients with AIDS. In addition to functioning as a central nervous system stimulant, METH has diverse effects on host immunity. Using a systemic mouse model of infection and in vitro assays in order to critically assess the impact of METH on C. neoformans pathogenesis, we demonstrate that METH stimulates fungal adhesion, glucuronoxylomannan (GXM) release, and biofilm formation in the lungs. Interestingly, structural analysis of the capsular polysaccharide of METH-exposed cryptococci revealed that METH alters the carbohydrate composition of this virulence factor, an event of adaptation to external stimuli that can be advantageous to the fungus during pathogenesis. Additionally, we show that METH promotes C. neoformans dissemination from the respiratory tract into the brain parenchyma. Our findings provide novel evidence of the impact of METH abuse on host homeostasis and increased permissiveness to opportunistic microorganisms. Importance: Methamphetamine (METH) is a major health threat to our society, as it adversely changes people’s behavior, as well as increases the risk for the acquisition of diverse infectious diseases, particularly those that enter through the respiratory tract or skin. This report investigates the effects of METH use on pulmonary infection by the AIDS-related fungus Cryptococcus neoformans. This drug of abuse stimulates colonization and biofilm formation in the lungs, followed by dissemination of the fungus to the central nervous system. Notably, C. neoformans modifies its capsular polysaccharide after METH exposure, highlighting the fungus’s ability to adapt to environmental stimuli, a possible explanation for its pathogenesis. The findings may translate into new knowledge and development of therapeutic and public health strategies to deal with the devastating complications of METH abuse.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Washington, Seattle, WA (United States)

Sponsoring Organization:: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Irma T. Hirschl/Monique Weill-Caulier Trust; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: FG02-00ER41132

OSTI ID:: 1626103

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 4 Vol. 4; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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