Cigarette smoke makes MRSA more aggressive

Antibiotic-resistant methicillin-resistant Staphylococcus aureus (MRSA) exposed to cigarette smoke become even more resistant to killing by the immune system, according to a study published in Infection and Immunity.

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, and colleagues, used in-vitro models to study the interaction between cigarette smoke-exposed MRSA and cells of innate immunity (macrophages and epithelial cells). They also studied characteristics of the bacterial surface in vitro. Researchers used a mouse model of pneumonia to demonstrate that cigarette smoke-exposed MRSA leads to more bacteria in the lungs and higher mortality rates.

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Crotty Alexander“MRSA is no longer isolated to nosocomial infections,” said 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.

“It is present in 20% to 30% of the population, and the nasopharynx is one of the sites it colonizes,” Dr Crotty Alexander said. “Because we found that cigarette smoke changes the virulence of this superbug, and these changes persist for days, the more virulent form of the bug can be spread from cigarette exposed individuals-smokers and those exposed to second-hand and third-hand smoke-to the rest of the population through contact. Thus, our findings are important to the whole population, not just smokers. Determining how cigarette smoke exposure makes MRSA more virulent-aggressive and able to cause invasive disease and death-will help guide therapeutic decision making, by targeting pathways that are still effective against this bacteria."

Dr Crotty Alexander’s message is simple: Stop smoking.

According to the American Lung Association, cigarette smoking is the number 1 cause of preventable disease and death worldwide. Every year in the United States more than 392,000 people die from tobacco-caused disease. Another 50,000 people die from exposure to second-hand smoke.

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“Cigarette smoke yet again has been found to be bad for human health,” she said. “In this era of increasing microbial resistance to antibiotics, trying to halt processes which lead to increased resistance is imperative. Cigarette smoke drives resistance to host antimicrobial peptides-very similar in structure and function to daptomycin-and macrophage killing in general, thus continuing the campaign against smoking is important.”

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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.

More MRSA coverage from our sister publication Dermatology Times.

“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,” Crotty Alexander said. “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, according to Crotty Alexander.

“Now we have evidence that cigarette smoke-induced resistance in MRSA may be an additional contributing factor,” she said.

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