A new study led by researchers with the New York University (NYU) School of Medicine is providing insight into how a unique strain of virulent and antibiotic-resistant community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) spread within a community and how genomic sequencing technology could prevent wider spread of community-based infections.
The findings appear in the Proceedings of the National Academy of Sciences.
Identifying a high-risk population
The strain of CA-MRSA, a variant of the USA300 strain that is dominant in the United States and is known for causing skin infections in settings where people have frequent skin-to-skin contact, began to appear in children from an Orthodox Jewish community in Brooklyn starting around 10 years ago. Most of the children were presenting with skin and other soft-tissue infections.
While it wasn't an outbreak by definition, infectious disease clinicians at NYU Langone Health noted that the frequency of the infections seemed to be higher in children from the Orthodox Jewish community. They asked study co-author Bo Shopsin, MD, PhD, director of epidemiology at NYU Langone Health and a professor of medicine at NYU School of Medicine, to look into it.
An initial investigation of more than 4,300 pediatric patients admitted to the hospital from May 2015 to December 2016 confirmed what the clinicians had observed; the risk for CA-MRSA infection among children from Orthodox-associated zip codes was 10-fold higher than children from other New York City zip codes, and risk for colonization was twice as high. It's the first known correlation between the Orthodox Jewish community and risk of MRSA infection.
"You could see that the cases were clustering by zip code, so we knew it wasn't necessarily a problem in the hospital," Shopsin told CIDRAP News.
Shopsin and his colleagues don't know how the strain began to spread within the Orthodox Jewish community in Brooklyn, but they suspect it might have started in daycare centers catering to the community, and then likely spread through households. That's typically how MRSA strains spread in high-risk communities where people have close contact.
"Daycare centers, inmates in correctional facilities, professional sports participants, a lot of different populations are at risk for having something like this happen," Shopsin said. "This is a larger group…but it's a high-risk population that probably has characteristics similar to other high-risk populations."
Future studies will explore the particular risk factors in Brooklyn's Orthodox Jewish community. But for this study, the researchers wanted to understand the genomic characteristics of the strain and how it evolved.
To do that, they analyzed MRSA isolates from 92 infected community members, 84 of whom were children. Molecular typing of the isolates showed that all were a clone of the epidemic USA300 lineage, and comparing the genome sequences with those of control isolates of USA300 MRSA and other USA300 strains from New York revealed that the Brooklyn isolates were unique and belonged to their own sub-clade, which the researchers named USA300-BKV.
Further analysis of the isolates' DNA fingerprint uncovered what made the USA300-BKV strain unique and enabled it to thrive. One was a mutation to a gene, pyrR, that enhanced the strain's ability to colonize the gastrointestinal tract of MRSA patients, giving it a fitness advantage. The other was the presence of a novel bacteriophage that essentially rewired the strain to promote large skin abscesses, a factor that could play a role in making the MRSA strain more contagious. "Abscesses probably promote transmission," Shopsin said. "That's why you cover wounds in hospitals."
Finally, the isolates also contained plasmids—mobile pieces of DNA that can be acquired from other bacteria—that harbored genes conferring resistance to mupirocin and chlorhexidine, the two topical antibiotics that are the mainstays for controlling and preventing the spread of MRSA.
Those resistance genes, which the researchers believe were acquired from Staphylococcus epidermidis bacteria, enhanced the strain's ability to fend off decolonization efforts, enabling it to continue spreading in the community. "It's probably likely that the doctors in the community were trying to decolonize patients to prevent recurrent infections…but the strain responded by becoming resistant," Shopsin explained.
Shopsin said the findings suggest the evolution of virulent, resistant CA-MRSA clones is a two-step process in which virulence evolves first and resistance is acquired later, and that high-risk communities can serve as incubators for these strains.
"First the strain gets adapted to the environment, and that adaption promotes spread and transmission. Once that happens, you have a clone that then spreads efficiently and is outcompeting its neighbors," he said. "Adaptation and expansion begets a clinical response; people start getting infections, they go see their doctors and they start getting antibiotics, and that clinical response is what selects for antibiotic resistance."
The concern is that CA-MRSA strains like USA300-BKV can spread beyond the communities where they evolved and get into hospitals and the general population. Shopsin said he and his colleagues are looking to see if the virulence and resistance elements that characterize USA300-BKV have made it into other MRSA strains in New York. "It remains to be seen whether that has happened or not," he said.
But the study also has important implications for future efforts to control strains of CA-MRSA. Shopsin thinks genomic sequencing technology, which wasn't readily available when clinicians first started noticing the cluster of CA-MRSA infections, could be applied more vigilantly to community-based disease surveillance. Instead of waiting for an outbreak to appear and then investigate, clinicians could respond to community-based disease clusters early on and break transmission before the resistant pathogens spread.
"Genomic surveillance, prospectively done, might change the way we do surveillance," he said. "We would be able to see not only what's going in hospitals, but we would actually have a window into the community."
Jan 7 Proc Natl Acad Sci USA study