UCSD: Methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant superbug, can cause life-threatening skin, bloodstream and surgical site infections or pneumonia. Researchers at the University of California, San Diego School of Medicine now report that cigarette smoke may make matters worse. The study, published March 30 by Infection and Immunity, shows that MRSA bacteria exposed to cigarette smoke become even more resistant to killing by the immune system.
“We already know that smoking cigarettes harms human respiratory and
immune cells, and now we’ve shown that, on the flipside, smoke can also
stress out invasive bacteria and make them more aggressive,” said senior
author Laura E. Crotty Alexander, MD, assistant clinical professor of
medicine at UC San Diego and staff physician at the Veterans Affairs San
Diego Healthcare System.
Crotty Alexander is a pulmonologist who sees many patients who smoke
cigarettes. She also sees many MRSA infections, and that got her
wondering if one might influence the other. To test the hypothesis,
Crotty Alexander and her team infected macrophages, immune cells that
engulf pathogens, with MRSA. Some of the bacteria were grown normally
and some were grown with cigarette smoke extract. They found that while
the macrophages were equally able to take up the two bacterial
populations, they had a harder time killing the MRSA that had been
exposed to cigarette smoke extract.
To better understand why, the Crotty Alexander team tested the
bacteria’s susceptibility to individual mechanisms macrophages typically
employ to kill bacteria. Once inside macrophages, smoke-exposed MRSA
were more resistant to killing by reactive oxygen species, the chemical
burst that macrophages use to destroy their microbial meals. The team
also discovered that smoke-exposed MRSA were more resistant to killing
by antimicrobial peptides, small protein pieces the immune system uses
to poke holes in bacterial cells and trigger inflammation. The effect
was dose-dependent, meaning that the more smoke extract they used, the
more resistant the MRSA became.
MRSA treated with cigarette smoke extract were also better at
sticking to and invading human cells grown in the lab. In a mouse model,
MRSA exposed to cigarette smoke survived better and caused pneumonia
with a higher mortality rate.
The data suggest that cigarette smoke strengthens MRSA bacteria by
altering their cell walls in such a way that they are better able to
repel antimicrobial peptides and other charged particles.
“Cigarette smokers are known to be more susceptible to infectious
diseases. Now we have evidence that cigarette smoke-induced resistance
in MRSA may be an additional contributing factor,” Crotty Alexander
Study co-authors include Elisa K. McEachern, John H. Hwang, Katherine
M. Sladewski, UC San Diego and Veterans Affairs San Diego Healthcare
System; Shari Nicatia, UC San Diego, Veterans Affairs San Diego
Healthcare System and Utrecht University; Carola Dewitz, UC San Diego,
Veterans Affairs San Diego Healthcare System and University of
Veterinary Medicine, Hannover, Germany; Denzil P. Mathew, Veterans
Affairs San Diego Healthcare System; and Victor Nizet, UC San Diego.
This research was funded, in part, by the U.S. Department of Veterans Affairs.