Researchers identify bacterial enzyme that can cause fatal heart conditions with pneumonia infections

Researchers Identify Bacterial Enzyme that can Cause Fatal Heart Conditions with Pneumonia Infections

The Enzyme Could Become a Target for Future Vaccines or Drug Therapies

BALTIMORE, Dec. 4, 2025: Pneumonia is a disease that burdens the healthcare system with more that 1.2 million emergency room visits each year and more than 41,000 adult deaths in the United States. Worldwide, more than one million children under the age of five die of the disease annually. But while past research has focused on the lungs, it can trigger heart complications—such as heart failure, arrhythmias, or heart attacks—that cause death.

Now, researchers from the University of Maryland School of Medicine (UMSOM) and the University of Alabama at Birmingham’s Heersink School of Medicine have identified a bacterial enzyme that may be the reason some people get heart complications with pneumonia, while others do not. Since enzymes create chemical reactions to help bacteria survive, grow, and sometimes attack tissues, the researchers understood this particular enzyme, named zmpB, could become a target for future vaccines or drug therapies. They published their findings in Cell Reports on Dec. 4.

“About one in five people hospitalized with pneumonia will suffer a life-threatening adverse cardiac event and, even in the years following, are at least twice as likely to experience some form of heart failure,” said the study’s lead author Carlos J. Orihuela, PhD, Professor of Microbiology at the University of Alabama at Birmingham.

While there are several bacteria and viruses causing pneumonia, the team looked specifically at Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. They used bacterial genome-wide association studies (bGWAS), mouse models, and cardiac organoids to confirm and make the discovery that S. pneumoniae can directly damage the heart and that zmpB potentiates the invasion of S. pneumoniae into the heart, respectively.

“This role for zmpB is totally new and this information now makes it a potential treatment target” said Orihuela.

“When we examined hundreds of strains isolated from patients who developed heart complications and compared those with bacteria from patients who only experienced pneumonia, a pattern immediately jumped out at us. Patients with heart failure were more frequently infected with a version of S. pneumoniae that carried the gene zmpB with a distinctive genetic trait, FIVAR domains, which are special segments that help the bacteria invade and survive within heart cells and cause pockets of infection,” said Adonis D’Mello, PhD, Bioinformatics Analyst in the group of Hervé Tettelin, PhD, Professor of Microbiology and Immunology at UMSOM and the Institute for Genome Sciences, both authors on the study. “In fact, it turns out that we found the more FIVAR domains this gene has, which so far had no characterized function, the more damage to the heart it causes.”

The researchers infected mice with either a regular pneumonia strain or with a genetically modified strain where they knocked out the zmpB gene and monitored disease progression. They found that mice infected with the normal strain developed numerous cardiac microlesions and cell death that damaged the heart, but those who had the knocked-out strain had few or no microlesions or cell death around their hearts.

Next, they exposed heart organoids—beating cardiac cells grown from human stem cells in a petri dish—to one of three tests: infecting them with pneumococcal strains with and without the zmpB gene as well as different versions of zmpB. Those with zmpB with FIVAR domains attached and invaded heart cells, whereas those that lacked the FIVAR domains had reduced heart tissue cell death and bacterial entry.

“With the mouse models, we learned that injury to the heart depended on the zmpB expressed by the strain, and with the organoids, we learned that it happens because the proteins equipped with FIVAR  domains help bacteria invade heart cells and damage them,” Dr. Tettelin said.

“Our hope is that by understanding these molecular fingerprints we can better protect patients against the risk of heart damage during an illness with pneumonia or at least minimize the severity,” Dr. Orihuela said. “Although more work needs to be done before it’s ready for the clinic, it may be possible that with a simple genetic test, doctors could identify high-risk strains of the bacteria early in an infection for closer cardiac monitoring or a targeted treatment to prevent heart damage.”

"These are extremely important findings,” said Mogens Kilian DMD, DSc, Dr. hc, FKC, R1, Professor Emeritus of Medical Microbiology at Aarhus University in Denmark, who is an expert in the field but did not participate in this research. “Not only does the study identify a function of an enigmatic enzyme in Streptococcus pneumoniae, it also explains the pathogenesis of serious complications associated with infections caused by some strains of this pathogen, and thereby, opens a potential route to prevention."

About the Institute for Genome Sciences

The Institute for Genome Sciences' (IGS) has been part of the University of Maryland School of Medicine (UMSOM) since 2007. IGS scientists work in diverse areas, applying genomics and systems biology approaches to better understand health issues to create a healthier Maryland and world. Our research spans multiple areas including cancer and precision medicine; parasitic, fungal, and bacterial diseases; sexual and reproductive health; the underpinnings of aging; and neuroscience areas including brain development, addiction, and mental health IGS also remains at the forefront of high-throughput genomic technologies and bioinformatics analyses through its core facility, Maryland Genomics which provides researchers around the world with cutting-edge, collaborative, and cost-effective sequencing and analysis.

About the University of Maryland School of Medicine

The University of Maryland School of Medicine, established in 1807 as the first public medical school in the U.S., continues today as one of the fastest growing, top-tier biomedical research enterprises in the world. The School has nearly $500 million total research funding, 46 departments, centers, and institutes, more than 2,200 student trainees and over 3,000 faculty members, including notable members of the National Academy of Medicine. As the largest public medical school in the DC/MD/VA region, faculty-physicians are working to help patients manage chronic diseases like obesity, cancer, heart disease and addiction, while also working on cutting-edge research to address the most critical generational health challenges. In 2024, the School ranked #12 among public medical schools and #27 among all medical schools for R&D expenditures by the National Science Foundation. With a $1.3 billion total operating budget, the School partners with the University of Maryland Medical Center to serve nearly 2 million patients annually. The School's global reach extends around the world with research and treatment facilities in 33 countries.  In Maryland, the School of Medicine is spearheading new initiatives in AI and health computing and partnering with the University of Maryland BioPark to develop new medical technologies and bioengineering ventures. For more information, visit medschool.umaryland.edu.

About the UAB Marnix E. Heersink School of Medicine

With more than 800 medical students and a faculty of more than 1,200, the Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham, a part of the University of Alabama System, is one of the premier academic medical centers in the United States. UAB is in the top four percent in research funding from the National Institutes of Health among public universities and is routinely listed among the best in various national rankings. UAB’s Medical-Scientist Training Program (M.D.-Ph.D.), Rural Medical Scholars Program and Early Medical School Acceptance Program are a few of the innovations on campus that foster collaboration across a multitude of disciplines. As the educational arm of UAB Medicine, the school trains students and residents in a world-class setting; UAB Hospital’s 1,400 beds place it as the 8th largest hospitals in the country. Doctoral students in UAB’s Graduate Biomedical Sciences Program participate in interdisciplinary thematic programs that integrate more than 25 departments and 20 research centers across UAB. Learn more at www.uab.edu. 

 

 

 

 

END