use can make a person more susceptible to the lung infection cryptococcosis,
according to a study published in mBio®, the online open-access journal of the
American Society for Microbiology.
found that injected methamphetamine (METH or Tik) significantly enhanced colonisation
of the lungs by Cryptococcus neoformans and accelerated progression of the
disease and the time to death in mouse models. C. neoformans is usually
harmless to healthy individuals, but METH causes chinks in the blood-brain
barrier that can permit the fungus to invade the central nervous system, where
it causes a deadly brain infection.
highest uptake of the drug is in the lungs," says corresponding author
Luis Martinez of Long Island University-Post, in Brookville, New York and of
Albert Einstein College of Medicine in The Bronx. "This may render the
individual susceptible to infection. We wanted to know how METH would alter C.
people in the US have abused METH in their lifetimes, and regular METH users
numbered approximately 353 000 in 2010, the most recent year for which data are
available. A central nervous system stimulant that adversely impacts
immunological responses, recent studies show that injected METH accumulates in
various sites in the body, but the lungs seem to accumulate the highest
concentrations, says Martinez, which could well impact how the lung responds to
the impact this accumulation might have on pulmonary infection, Martinez and
his colleagues injected mice with doses of METH over the course of three weeks,
then exposed those mice to the C. neoformans fungus. In humans, C. neoformans
initially infects the lungs but often crosses the blood-brain barrier to infect
the central nervous system and cause meningitis. In their experiments, METH
significantly accelerated the speed with which the infected mice died, so that
nine days after infection, 100% of METH treated mice were dead, compared to 50%
of the control mice.
fluorescent microscopy to examine lung tissue in METH-treated and control mice,
the researchers found that METH enhanced the interaction of C. neoformans with
epithelial cells in the lining of the lung. Seven days after exposure to the
fungus, the lungs of METH-treated mice showed large numbers of fungi surrounded
by vast amounts of gooey polysaccharide in a biofilm-like arrangement.
METH-treated mice also displayed low numbers of inflammatory cells early during
infection and breathed faster than controls, a sign of respiratory distress.
says this greater ability to cause disease in the lung may be due in part to
simple electrical attraction. Their analysis shows that METH imparts a greater
negative charge on the surface of the fungal cells, possibly lending them a
greater attraction to the surface of the lung and an enhanced ability to form a
biofilm that can protect its members from attack by the immune system. The
fungus also releases more of its capsular polysaccharide in METH-treated mice,
which can help the organism colonize and persist in the lung.
the organism senses the drug, it basically modifies the polysaccharide in the
capsule. This might be an explanation for the pathogenicity of the organism in
the presence of the drug, but it also tells you how the organism senses the
environment and that it will modify the way that it causes disease,"
fungus doesn't stop in the lungs. "The drug stimulates colonisation and
biofilm formation in the lungs of these animals," says Martinez. "And
this will follow to dissemination to the central nervous system by the
neoformans in the lung moved on to the bloodstream and then into the central
nervous system. The brains of METH-treated mice had higher numbers of C.
neoformans cells, greater quantities of the fungus' polysaccharide, and larger
lesions than control mice, indicating that METH has a detrimental effect on the
blood-brain barrier, permitting the pathogen to cross more easily from the
bloodstream to infect the central nervous system.
alterations to the molecules responsible to maintain the integrity of the
blood-brain barrier provide an explanation for the susceptibility of METH
abuser to brain infection by HIV and other pathogens," write the authors.
and his colleagues plan to follow up on the work by investigating how aspects
of the immune system might be involved in changes the drug causes to the