When infectious diseases specialist Michael David was in medical school at Yale in the 1990s, almost no one on the U.S. East Coast had community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. In fact, he says, if patients presented with a skin infection, he and his colleagues would ask the patient if he or she had been in the hospital. If they hadn’t, “you would not treat them for a MRSA infection because it was almost impossible that they would get one.”
But since then new strains have rapidly evolved and merged, he says. Some regular strains of S. aureus picked up a novel genetic cassette and became MRSA. These new strains were so common and so able to spread rapidly that by 2004 they became the most common cause of skin infections in patients coming to urban emergency rooms in the U.S.
David and colleagues have been studying the evolution of MRSA. Their newest work, published this week in mBio, suggests that households can serve as a reservoir for transmitting MRSA: Once the bacterium enters a home, it can linger for years, spreading from person to person and evolving genetically to become unique to that household.
For the study, coauthor Timothy D. Read, PhD, an associate professor of infectious diseases at the Emory University School of Medicine in Atlanta and Tauqeer Alam, a postdoctoral fellow at Emory, performed whole genome sequencing on 146 isolates of USA300 MRSA – the predominant community-associated strain of MRSA, which is virulent and easily transmissible. These isolates were collected during a previous study from 21 households in Chicago and Los Angeles where a family member had presented to the emergency room with a skin infection found to be caused by USA300 MRSA. During that study, published in Clinical Infectious Diseases in 2012, investigators visited the homes of 350 skin infection patients, culturing their and their family members’ noses, throats and groins. Among 1,162 people studied (350 skin infection patients and 812 household members), S. aureus colonized at one or more body sites 40 percent (137 of 350) of patients with skin infections and 50 percent (405 of 812) of their household contacts.
For the current study, Dr. Alam evaluated the genome data to understand transmission dynamics, genetic relatedness, and microevolution of USA300 MRSA within households. He and the study coauthors also compared genetic information from these MRSA samples with previously published genome sequences of 35 USA300 MRSA isolates from San Diego, 277 USA300 MRSA isolates from New York City, and the completed genomes of the USA300 strains TCH1516 and FPR3757. Dr. Alam created a phylogenetic tree to show the relationships among the bacterial strains.
The researchers found that isolates within households clustered into closely related groups, suggesting a single common USA300 ancestral strain was introduced to and transmitted within each household. Researchers also determined from Bayesian evolutionary reconstruction that USA300 MRSA persisted within households from 2.3 to 8.3 years before their samples were collected, and that in the course of a year, USA300 strains had about a 1 in a million chance of having a random genetic change at any place in the genome, estimating the speed of evolution in these strains. Researchers also found evidence that USA300 clones, when persisting in households, continued to acquire extraneous DNA.
“USA300 MRSA strains within households were more similar to each other than those from different households,” says David, an assistant professor of medicine at the University of Chicago. Although MRSA is introduced into households rarely, he says, once it gets in, “it can hang out there for years, ping-ponging around from person to person. Our findings strongly suggest that unique USA300 MRSA isolates are transmitted within households that contain an individual with a skin infection.”
USA300 broke down into two big clades, with the vast majority of isolates from Los Angeles genetically different from those in Chicago. Fluoroquinolone-resistant USA300 clones emerged around 1995 and were more widespread in Los Angeles, San Diego and New York City than in Chicago.
“The study adds to the knowledge base of how USA300 MRSA has spread throughout the country,” says Dr. Read. “We’re also getting hints at how it evolves inside households. Decolonization of household members may be a critical component of prevention programs to control USA300 MRSA spread in the United States.”
Continuing work will look at potential interventions in households to prevent new infections among cohabitants and potential interventions to try to eliminate the bacteria from households, David says. He’s also interested in figuring out whether the bacteria evolve to become more or less virulent, and teasing out risk factors for recurrent MRSA infections.
-- Karen Blum