Investigating the Relationship Between MRSA and the Lymphatic System

Dennis Jones, PhD

Dennis Jones, PhD, is a postdoctoral fellow in the Edwin L. Steele Labs at Massachusetts General Hospital. Dr. Jones won an award for a poster detailing the results of a research study that shows how MRSA infections contribute to recurrences of lymphedema by damaging muscle cells with bacterial toxins.

Continue reading to learn more about his team’s research:

Fourteen million people develop bacterial infections in their skin and soft tissues each year in the United States, with about 40% of these infections due to a difficult to treat bacteria called methicillin-resistant Staphylococcus aureus (MRSA). About 500,000 patients are hospitalized annually because of these infections; many of whom will endure repeated infections over the subsequent months and years.

Patients with lymphedema – swelling and fluid buildup caused by damage to or malformation of the lymphatic system – are particularly prone to recurrent infections like MRSA.

The lymphatic system is a network of tissues and organs that recycles biomolecules, eliminates waste, and facilitates specific immune responses to foreign material. Normal lymphatic function relies on a balance of fluid between the lymphatic vessels and the blood stream. Lymphatic muscle cells are critical for this fluid transport in that they contract and squeeze lymphatic vessels to move the fluid toward blood circulation. When this process is interrupted due to genetic abnormalities or physical damage to lymphatic vessels, lymphedema can occur.

Each MRSA infection further damages the lymphatic system and may lead to lymphedema or exacerbate existing lymphedema. Impairment of the lymphatic system increases the risk for infection, creating a vicious cycle of bacterial infection followed by lymphatic vessel damage and deteriorating lymphatic function.

Studying the relationship between bacterial infections and lymphedema

While we know that bacterial infections are a consequence of lymphedema, our study was the first of its kind to investigate the inverse relationship to see how bacterial infections impact lymphatic function.

To understand this relationship, we created a skin infection model using a strain of MRSA commonly found in human skin and soft tissue infections.

When we studied the model during bacterial infection, we found that lymphatic contraction and fluid flow within lymphatic vessels were reduced.

We were surprised to find that lymphatic function didn’t improve after the infection was cleared. Lymphatic muscle cell regeneration was incomplete and the lymphatic vessels’ ability to contract and transport fluid remained inhibited. We discovered that MRSA-derived toxins had killed lymphatic muscle cells, which are critical for lymphatic contraction.

Our study shows that MRSA infections permanently impair lymphatic function, potentially explaining why many patients have frequent recurrent infections. Our results suggest that inhibiting toxin production could be a potential therapeutic strategy to limit damage in patients prone to recurring bacterial infections.

Discovering this basic mechanism of how MRSA alters the body’s ability to fight infection will facilitate the development of drugs to maintain lymphatic function during and after MRSA infections, ultimately protecting patients from future infections.

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