Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
JournalmBio
Volume4
Issue number4
DOIs
StatePublished - Jul 30 2013

Fingerprint

Cryptococcus neoformans
Methamphetamine
Lung
Brain
Infection
Fungi
Street Drugs
Biofilms
Respiratory System
Polysaccharides
Fungal Meningitis
Acquired Immunodeficiency Syndrome
Permissiveness
Central Nervous System Stimulants
Cryptococcus
Aptitude
Virulence Factors
Communicable Diseases
Immunity
Homeostasis

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Patel, D., Desai, G. M., Frases, S., Cordero, R. J. B., DeLeon-Rodriguez, C. M., Eugenin, E. A., ... Martinez, L. R. (2013). Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain. mBio, 4(4). https://doi.org/10.1128/mBio.00400-13

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.

In: mBio, Vol. 4, No. 4, 30.07.2013.

Research output: Contribution to journalArticle

Patel, D, Desai, GM, Frases, S, Cordero, RJB, DeLeon-Rodriguez, CM, Eugenin, EA, Nosanchuk, JD & Martinez, LR 2013, 'Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain', mBio, vol. 4, no. 4. https://doi.org/10.1128/mBio.00400-13
Patel D, Desai GM, Frases S, Cordero RJB, DeLeon-Rodriguez CM, Eugenin EA et al. Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain. mBio. 2013 Jul 30;4(4). https://doi.org/10.1128/mBio.00400-13
Patel, Dhavan ; Desai, Gunjan M. ; Frases, Susana ; Cordero, Radames J B ; DeLeon-Rodriguez, Carlos M. ; Eugenin, Eliseo A. ; Nosanchuk, Joshua D. ; Martinez, Luis R. / Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain. In: mBio. 2013 ; Vol. 4, No. 4.
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