MRSA
A microscopic scan of MRSA, a drug-resistant Staphylococcus aureus bacteria.
Credit: CDC/Janice Haney Carr

Infection with MRSA, a dangerous, drug-resistant form of Staphylococcus aureus (S. aureus), is unpleasant, to say the least.

It starts with painful, pus-filled bumps that create deep, painful abscesses that need to be surgically drained. Left untreated, bacteria can flood the body, causing life-threatening infections in the blood, bones and joints. 

There are more than 80,000 invasive MRSA infections – causing more than 11,000 deaths – in the U.S. each year, according to the Centers for Disease Control and Prevention.

But there is a strange twist: Research has shown that men are more at-risk to be infected by S. aureus than women. 

UNM researcher Pamela Hall, PhD, wants to know why this sex bias exists, and how the factors protecting women can be used to promote stronger immune system responses in men. 

Hall, an assistant professor of pharmaceutical sciences in the College of Pharmacy, is publishing a paper on her work concerning sex differences in S. aureus infections, and has received funding from the National Institutes of Health to discover new mechanisms that may help bolster mens’ immune response.

Scientists have known for some time that a gender bias exists in who gets infected by MRSA. “More men – and women on birth control – have been reported to be persistent carriers (of the bacteria),” Hall says. “Pre-menopausal women not on birth control are less likely to be carriers.” 

Some behavioral factors may contribute to the overall sex difference, she says. For example, women are generally more hygienic and thus are less likely to carry S. aureus on their skin. Also, mens’ skin is thicker than women’s, which may contribute to the different infection rates.

“Animal models also show that females are better at clearing the S. aureus in skin infection,” Hall says. But “if female sex organs are removed, they become susceptible to S. aureus infection.” Because the female sex organs produce estrogen, this suggests a direct connection between resistance to the infection and the hormone.

So what does estrogen do that testosterone does not? When activated by estrogen, estrogen receptors may help activate genes that are responsible for boosting the immune response, Hall says. Part of this dynamic response includes the production of neutrophils, cells that directly kill the bacteria, and macrophages, which decrease inflammation by cleaning up dead neutrophils. 

If a similar response could be stimulated in men, their immune system might kill S. aureus more efficiently and better fight antibiotic-resistant S. aureus, Hall says. Estrogen therapy in men is controversial, however, as injection of the hormone can cause unwanted effects.

Treatments used in current clinical trials target specific toxins produced by S. aureus to help the immune system kill the bacteria more efficiently. Other drugs may be developed to assist in promoting immune system defense, to increase the protective response.

Hall adds that anything that will advance the ability of the immune system to clear the microbes would have a broad effect – not just against staph, but potentially could be broadly effective against infections such as those caused by Streptococci or E. coli.

Understanding the sex bias in susceptibility to infection, Hall thinks, will have very powerful impact on future therapies aimed at targeting the person’s immune system to promote defense.