$4.4M From NIH Supports UMD Research On Use of Enzymes to Combat Pneumonia

The National Institutes for Health, (NIH) awarded $4.4M to Daniel Nelson, a professor in the Department of Veterinary Medicine and a Fellow in the Institute for Bioscience and Biotechnology Research, and his colleague Norberto Gonzalez-Juarbe, Associate Professor at the J. Craig Venter Institute (JCVI) to develop both a novel therapeutic and a vaccine approach to address Streptococcus pneumoniae, the leading cause of bacterial community-acquired pneumonia worldwide.

According to the World Health Organization, pneumococcal infection causes more than 1.6 million deaths annually, with children and the elderly being the most vulnerable. Pneumococcal vaccinations are very effective, but they target just a few of the more than 100 different strains of pneumococcus, and they are sometimes unavailable in many developing countries.

Additionally, antimicrobial resistance is on the rise globally, and poses an escalating risk of pneumococcal disease that is increasingly difficult to combat.  One new strategy being developed to circumvent the problem of antimicrobial resistance is the use of endolysins, enzymes that can kill bacteria by degrading the bacterial cell wall upon contact. Endolysins represent an alternative to traditional vaccines and antibiotics, and because they function in a species-specific manner, they only affect pathogenic bacteria while sparing "good" bacteria.

Nelson and Gonzalez-Juarbe will be investigating this new strategy with the help of this new grant. Their research proposal, titled “Endolysins as tools to eradicate pneumococcal biofilms and development of protective immunity,” has two primary goals. First, endolysins will be directly evaluated for their ability to treat active pneumococcal infection. Next, the researchers will use endolysins to cause necroptosis, a form of cell death that initiates the development of protective immunity against colonizing bacteria.

“The use of an endolysin to induce localized necroptosis via bacterial lysis should have a significant impact on development of serotype-independent protective immunity against colonizing bacteria,” said Gonzalez-Juarbe. 

Pneumococcal antigens will be released as a result of endolysin-induced bacterial lysis, and when combined with localized necroptosis activity, they are anticipated to aid in the development of an effective immune response to future pneumococcal exposure. In this way, endolysin therapy would provide long-lasting, serotype-independent immunity.

“We have spent many years doing basic research to engineer and optimize the perfect pneumococcal endolysin. Now we are finally ready to move forward with the infection and efficacy studies supported by this award,” said Nelson. 

This article was adapted from the original text on the IBBR website.