Pneumonia, a disease that takes a toll on global health, is responsible for over 1.2 million emergency room visits and a staggering 41,000 adult deaths annually in the United States alone. Worldwide, it claims the lives of more than one million children under five each year. But here's where it gets controversial: while pneumonia's impact on the lungs has been well-studied, its ability to trigger life-threatening heart complications, including heart failure, arrhythmias, and heart attacks, has been less explored.
Researchers from the University of Maryland School of Medicine (UMSOM) and the University of Alabama at Birmingham's Heersink School of Medicine have made a groundbreaking discovery. They've identified a bacterial enzyme, zmpB, which may be the key to understanding why some individuals develop heart complications from pneumonia while others do not. Enzymes are like the bacteria's secret weapons, aiding their survival and growth, and sometimes, their attack on our tissues.
"One in five people hospitalized with pneumonia faces a life-threatening cardiac event, and even years later, they are twice as likely to experience heart failure," warns Carlos J. Orihuela, PhD, a Professor of Microbiology at the University of Alabama at Birmingham and the lead author of the study.
The team focused on Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. Using advanced techniques like bacterial genome-wide association studies (bGWAS), mouse models, and cardiac organoids, they confirmed that S. pneumoniae can directly damage the heart. The zmpB enzyme was found to potentiate the invasion of S. pneumoniae into the heart.
"This role for zmpB is entirely new, and now it's a potential target for future treatments," Orihuela emphasizes.
Adonis D'Mello, PhD, a Bioinformatics Analyst involved in the study, explains: "When we compared the strains from patients with heart complications to those with pneumonia only, we noticed a pattern. Patients with heart failure were more often infected with an S. pneumoniae version carrying the zmpB gene, which has a unique genetic trait called FIVAR domains. These domains help the bacteria invade heart cells, survive within them, and cause infection pockets."
The researchers infected mice with either a regular pneumonia strain or a modified strain lacking the zmpB gene. They found that mice with the normal strain developed cardiac microlesions and cell death, damaging their hearts. In contrast, those with the knocked-out strain had minimal or no microlesions or cell death around their hearts.
Next, they exposed heart organoids (beating cardiac cells grown from human stem cells) to different pneumococcal strains and versions of zmpB. Those with zmpB and FIVAR domains invaded heart cells, while those without FIVAR domains showed reduced heart tissue cell death and bacterial entry.
"The mouse models taught us that the injury depended on the zmpB expressed by the strain, and the organoids showed us why: proteins with FIVAR domains help bacteria invade heart cells and cause damage," explains Hervé Tettelin, PhD, Professor of Microbiology and Immunology at UMSOM and the Institute for Genome Sciences.
"By understanding these molecular fingerprints, we hope to protect patients from heart damage during pneumonia or at least reduce its severity," Orihuela says. "With further research, a simple genetic test might identify high-risk bacterial strains early, allowing for closer cardiac monitoring or targeted treatments."
Mogens Kilian DMD, DSc, Dr. hc, FKC, R1, Professor Emeritus of Medical Microbiology at Aarhus University, Denmark, who was not involved in the research, calls it "extremely important." He adds, "It not only identifies an enigmatic enzyme's function but also explains the pathogenesis of serious complications, opening a potential route to prevention."
The study, "Allele-specific Zinc Metalloprotease B influences cardiac damage during invasive pneumococcal disease," was published in Cell Reports on December 4, 2025.
So, what do you think? Could this research lead to a breakthrough in pneumonia treatment and prevention? Share your thoughts in the comments!
