Bold claim: a single bacterial enzyme may explain why some pneumonia patients suffer serious heart problems while others do not. This is the core idea researchers are exploring, and it could change how pneumonia is treated and monitored.
A team from the University of Maryland School of Medicine and the University of Alabama at Birmingham has identified a specific enzyme from Streptococcus pneumoniae, named zmpB, as a potential driver of heart complications in pneumonia cases. Enzymes drive chemical reactions that help bacteria survive, grow, and sometimes invade tissues. The researchers propose that zmpB could become a target for future vaccines or therapies aimed at preventing cardiac damage during pneumonia. The study was published in Cell Reports on December 4.
Key findings include:
- Bacterial factor linked to cardiac events – Researchers found that zmpB is a key factor in why some pneumonia patients experience serious heart issues, such as heart failure or heart attacks.
- How heart damage occurs – Pneumococcal strains carrying zmpB, particularly versions with specialized FIVAR domains, more effectively invade heart cells, leading to microlesions and cell death. This was demonstrated in mouse models and in human heart organoids (lab-grown beating heart tissue from stem cells).
- Implications for care – Detecting zmpB-positive strains could enable early risk assessment, closer cardiac monitoring, and the development of vaccines or treatments to prevent pneumonia-related heart damage.
Disease burden highlights the stakes. Pneumonia causes over 1.2 million emergency department visits and more than 41,000 adult deaths annually in the United States, and globally, more than a million children under five die from pneumonia each year. While the lungs are the primary site of pneumonia, life-threatening heart complications can occur and contribute to mortality.
The study specifically focused on Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. Using genome-wide association studies (bGWAS), mouse experiments, and heart organoids, the researchers showed that S. pneumoniae can directly harm the heart, with zmpB enhancing the bacteria’s ability to invade cardiac tissue.
Lead author Carlos J. Orihuela, PhD, emphasized the novelty of zmpB’s role and its potential as a treatment target. Adonis D’Mello, PhD, and Hervé Tettelin, PhD, added that the presence of zmpB with more FIVAR domains correlated with greater heart damage, suggesting these domains assist bacterial invasion and tissue injury.
In their experiments, mice infected with a normal pneumonia strain developed widespread heart lesions and cell death, whereas mice infected with a zmpB-knockout strain showed markedly fewer heart lesions. In parallel, human heart organoids exposed to zmpB-bearing strains with FIVAR domains experienced higher bacterial entry and tissue injury compared with strains lacking FIVAR domains.
The researchers concluded that the impact on the heart hinges on the specific zmpB variant carried by the bacterial strain. The FIVAR domains appear to drive the invasion of heart cells and subsequent damage. The team envisions future work that could include a genetic test to identify high-risk strains early in infection, enabling targeted cardiac monitoring or therapies to prevent heart injury.
External experts not involved in the study praised the work for clarifying how a previously enigmatic enzyme contributes to severe complications and for outlining a potential path to prevention.
Controversial angle and open questions. Some may question how widespread the zmpB-associated risk is across different patient populations or how best to implement routine genetic testing in clinical settings. Others might argue for broader research into whether intervening on zmpB could affect the bacteria’s viability or antibiotic resistance. What are your thoughts on prioritizing zmpB as a vaccine or therapeutic target in the fight against pneumonia-related heart damage? Join the discussion below.
