A pneumococcal enzyme, zmpB, is a key factor in some pneumonia patients develop serious heart complications.<\/p>\n
RT\u2019s Three Key Takeaways:<\/p>\n
Bacterial Driver of Cardiac Complications \u2013 Researchers identified a pneumococcal enzyme, zmpB, as a key factor explaining why some pneumonia patients develop serious heart complications such as heart failure or heart attacks.<\/p>\n
Mechanism of Heart Damage \u2013 Strains of Streptococcus pneumoniae carrying zmpB with specialized FIVAR domains can more effectively invade heart cells, causing cardiac microlesions and cell death, as shown in mouse models and human heart organoids.<\/p>\n
Future Clinical Impact \u2013 Identifying zmpB-positive strains could enable early risk stratification, targeted monitoring, and the development of vaccines or therapies aimed at preventing pneumonia-related heart damage.<\/p>\n
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\u2014such as heart failure, arrhythmias, or heart attacks\u2014that cause death.<\/p>\n
Now, researchers from the University of Maryland School of Medicine (UMSOM) and the University of Alabama at Birmingham\u2019s 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\u00a0zmpB, could become a target for future vaccines or drug therapies. They published their findings in\u00a0Cell Reports\u00a0on Dec. 4.<\/p>\n
\u201cAbout 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,\u201d said the study\u2019s lead author Carlos J. Orihuela, PhD, Professor of Microbiology at the University of Alabama at Birmingham.<\/p>\n
While there are several bacteria and viruses causing pneumonia, the team looked specifically at\u00a0Streptococcus 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\u00a0S. pneumoniae\u00a0can directly damage the heart and that\u00a0zmpB\u00a0potentiates the invasion of\u00a0S. pneumoniae\u00a0into the heart, respectively.<\/p>\n
\u201cThis role for\u00a0zmpB\u00a0is totally new and this information now makes it a potential treatment target\u201d said Orihuela.<\/p>\n
\u201cWhen 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\u00a0S. pneumoniae that carried the gene\u00a0zmpB\u00a0with 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,\u201d said Adonis D\u2019Mello, PhD, Bioinformatics Analyst in the group of Herv\u00e9 Tettelin, PhD, Professor of Microbiology and Immunology at UMSOM and the Institute for Genome Sciences, both authors on the study. \u201cIn 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.\u201d<\/p>\n
The researchers infected mice with either a regular pneumonia strain or with a genetically modified strain where they knocked out the\u00a0zmpB\u00a0gene 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.<\/p>\n
Next, they exposed heart organoids\u2014beating cardiac cells grown from human stem cells in a petri dish\u2014to one of three tests: infecting them with pneumococcal strains with and without the\u00a0zmpB\u00a0gene as well as different versions of\u00a0zmpB. Those with\u00a0zmpB\u00a0with FIVAR domains attached and invaded heart cells, whereas those that lacked the FIVAR domains had reduced heart tissue cell death and bacterial entry.<\/p>\n
\u201cWith the mouse models, we learned that injury to the heart depended on the\u00a0zmpB\u00a0expressed by the strain, and with the organoids, we learned that it happens because the proteins equipped with FIVAR \u00a0domains help bacteria invade heart cells and damage them,\u201d Dr. Tettelin said.<\/p>\n
\u201cOur 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,\u201d Dr. Orihuela said. \u201cAlthough more work needs to be done before it\u2019s 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.\u201d<\/p>\n
\u201cThese are extremely important findings,\u201d 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. \u201cNot only does the study identify a function of an enigmatic enzyme in\u00a0Streptococcus pneumoniae,\u00a0it 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.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"A pneumococcal enzyme, zmpB, is a key factor in some pneumonia patients develop serious heart complications. RT\u2019s Three…\n","protected":false},"author":2,"featured_media":168350,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[55816,100081,163,85,46,100082,100083,35750],"class_list":{"0":"post-168349","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-bacterial-pneumonia","9":"tag-cardiology-and-cardiovascular","10":"tag-health","11":"tag-il","12":"tag-israel","13":"tag-lung-infection-bacterial","14":"tag-pneumococcus","15":"tag-pneumonia"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/168349","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=168349"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/168349\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/168350"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=168349"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=168349"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=168349"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}