A multidisciplinary research team has identified a key mechanism by which the human bacterium Mycoplasma pneumoniae acquires essential lipids, including cholesterol, from the host body. This discovery, published in Nature Communications, was co-led by Dr. Noemí Rotllan, Dr. Marina Marcos, and Dr. David Vizarraga, with overall coordination by Dr. Joan Carles Escolà-Gil, Dr. Jaume Piñol, and Dr. Ignacio Fita.
P116 Protein and Lipid Uptake
The bacterium utilizes the P116 protein to capture cholesterol and other essential lipids, a process critical for its survival and ability to colonize tissues beyond the lungs. Mycoplasma pneumoniae, unlike many other bacteria, cannot synthesize many lipids necessary for its cell membrane and relies entirely on the host for these components.
Experiments showed that P116 rapidly incorporates cholesterol from human lipoproteins like LDL and HDL. It can also capture phosphatidylcholines, sphingomyelins, and triacylglycerols. This broad lipid uptake capacity allows Mycoplasma pneumoniae to adapt to various bodily environments and colonize lipid-rich tissues outside the respiratory system, which helps explain extra-respiratory clinical manifestations and potential contributions to systemic inflammatory processes.
Therapeutic and Biotechnological Implications
A monoclonal antibody specifically targeting the C-terminal domain of P116 has been found to block cholesterol uptake by the bacterium, which is essential for its survival. This antibody significantly reduces the growth of Mycoplasma pneumoniae in cell cultures and limits its ability to adhere to human atherosclerotic lesions in ex vivo samples.
Preventing this adhesion is considered important because the presence of Mycoplasma pneumoniae in vulnerable plaques may promote local inflammation and compromise plaque stability, potentially leading to cardiovascular events.
Researchers have also developed a modified, harmless version of the bacterium as a biotechnological tool. This modified microorganism retains its natural ability to localize to lipid-rich tissues. In studies with hypercholesterolemic mice, it selectively accumulated in the liver and atherosclerotic plaques, suggesting its potential as a vehicle for targeted delivery of therapeutic molecules or diagnostic agents.
Collaborative Effort
The study involved collaboration from institutions including the Sant Pau Research Institute (IR Sant Pau), Autonomous University of Barcelona (UAB), Institute of Molecular Biology of Barcelona (IBMB-CSIC), and the Center for Genomic Regulation (CRG), among others. This research provides a conceptual advance in understanding Mycoplasma pneumoniae and offers new avenues for developing antimicrobial therapies, vaccines, and biotechnological tools for metabolic and cardiovascular diseases.