Impact of MRSA on Lymphatic Function Studied by MGH Investigators

Investigators from Massachusetts General Hospital (MGH) have made some interesting findings regarding methicillin-resistant Staphylococcus aureus (MRSA) that may hold the key to curbing lymphatic repercussions.

According to the Centers for Disease Control and Prevention (CDC) approximately 2 in every 100 individuals carry MRSA. Although data on the incidence of the bacteria in the community is not available, studies have shown that about 500,000 individuals are hospitalized each year for serious MRSA infections and 10% of those patients will have a recurrent infection that requires readmission within a month.

Individuals who suffer from lymphedema are most likely to suffer reinfections, according to a press release on the MGH study, and these reinfections can further exacerbate the condition. Until this most recent study, however, investigators had yet to research “the potential interactions between bacterial infections and lymphatic function.”

Using a mouse model, investigators from MGH discovered that although MRSA cleared tissue infections within 30 days of infection and inflammation associated with the infection was gone within 60 days, the mice still showed abnormalities in their lymphatic vessels. In particular, “the lymphatic vessels in MRSA-infected tissues showed abnormalities—including increased vessel diameter and weaker, less frequent contractions—that were still present 120 days after the induction of infection. Close examination revealed that the number of lymphatic muscle cells surrounding lymphatic vessels was depleted as late as 260 days after infection.”

Senior author, Timothy Padera, PhD, of the Steele Laboratories for Tumor Biology in the MGH Department of Radiation Oncology, shared that the investigators expected that they would find that lymphatic function impairment measures would be similar to those seen during inflammation that was not infection-associated, but they discovered this was not the case. Dr. Padera is quoted in the press release as saying, “[W]hile lymph pumping was restored after the resolution of sterile inflammation, MRSA-induced impairment persisted long after the infection was resolved and the inflammation had stopped. This persistence long after bacteria have been cleared can be explained by the loss of lymphatic muscle cells."

Furthermore, the investigators found that both cultured mouse and human lymphatic or smooth muscles cells that were exposed to proteins produced by MRSA died. Analysis of the proteins revealed several known pathogenic toxins. The expression of most of these toxins is controlled by the accessory gene regulator (agr). “The team tested a mutant form of MRSA lacking the agr against several types of cultured cells and in their animal model,” according to the press release, and found that the mutated MRSA did not produce the killing proteins. In addition, “…lymphatic function—including the strength and frequency of vessel contraction—was significantly better in mice infected with the mutant strain than in animals infected with a non-mutated strain.”

The team postulates that these results suggest that targeting the agr during or after MRSA infection could have a profound positive impact on lymphatic function, at least in mice. The next steps for the team are to determine if humans experience similar impaired lymphatic function and then identify the MRSA toxins that act on the human lymphatic muscle cells.