A novel preventative and treatment for klebsiella pneumoniae infection

The National Institute of Allergy and Infectious Diseases awarded Virtici LLC $306,500 on September 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a first-in-class, orally administered probiotic therapy for treatment and prevention of Klebsiella pneumoniae gastrointestinal colonization, transmission, and infection. The award is a Project Grant with assistance type classification.

K. pneumoniae causes pneumonia, urinary tract infections, bloodstream infections, and other serious health conditions particularly in healthcare settings, and gastrointestinal colonization by certain strains contributes to inflammatory bowel disease and fatty liver disease. The rise of carbapenem-resistant, antibiotic-resistant K. pneumoniae strains limits treatment options and increases mortality. The project will exploit bacteriocins—antimicrobial peptides that bacteria naturally produce to outcompete related species in the gut microbiome—as a therapeutic strategy to address multidrug-resistant K. pneumoniae infections where traditional antibiotics are ineffective.

Performance is located in Washington and runs through August 31, 2028. Virtici LLC is a for-profit biomedical research and development company based in Seattle, Washington, with prior federal experience in vaccine research, immunological therapeutics, and infectious disease treatment development.

Abstract

Our goal is to develop a first-in-class, orally administered probiotic therapy for the treatment and prevention of klebsiella (K.) pneumoniae gastrointestinal (GI) colonization, transmission, and infection. K. Pneumoniae is a gram-negative, rod-shaped bacteria belonging to the family enterobacteriaceae. Among the numerous species within the genus, K. Pneumoniae stands out as a significant human pathogen, capable of causing a range of infections, from pneumonia and urinary tract infections to bloodstream infections, particularly in healthcare SETTINGS14, 15. GI colonization by certain K. Pneumoniae strains also contributes to the development of inflammatory bowel DISEASE16 and fatty acid liver DISEASE17. The rise of antibiotic resistance in klebsiella strains, fueled by the indiscriminate use of antibiotics, presents a grave concern globally. The emergence of carbapenem-resistant strains, often referred to as superbugs, poses a formidable challenge to healthcare systems, limiting treatment options and increasing mortality RATES14, 15, 18-20. Efforts to combat K. Pneumoniae infections encompass a multifaceted approach, including stringent infection control measures, surveillance programs, and the use of antibiotics. The human GUT microbiome is a densely populated ecosystem, where our bacterial symbionts are in constant competition for nutrients and SURVIVAL21. A major strategy employed by bacteria to outcompete their neighbors is the production of highly specific antimicrobial peptides, so called bacteriocins, that target closely related species or STRAINS22. While small molecule antimicrobials, such as PENICILLIN23, have been exploited for decades as traditional antibiotics, antimicrobial peptides as therapeutic agents have just recently gained widespread interest as potential treatments of MDR PATHOGENS24, 25. Class IIB microcins are ribosomally synthesized bacteriocins between 5 KDA to 10 KDA in size with activity against closely related strains or SPECIES1-3, 26, 27. Recently, our project team identified a novel class IIB microcin MCCI47 (ECI47) that demonstrated potent inhibition of numerous enterobacteriaceae, including multidrug-resistant clinical ISOLATES1, 5. We genetically engineered the probiotic bacterium escherichia coli nissle 1917 (ECN) to produce ECI47 from a stable multicopy plasmid. We then tested the clinical potential of the ECN-ECI47-producing probiotic in a murine carbapenem-resistant (CR) K. Pneumoniae colonization model and demonstrated significant ECN-ECI47- dependent reduction of CR K. Pneumoniae abundance after seven days of daily oral probiotic ADMINISTRATION1, 5. We have since identified a series of novel class IIB microcins that are more potent against K. Pneumoniae and other enterobacteriaceae species. Building from this work, our goal is to develop a first-in-class, orally administered, probiotic therapy for the treatment and prevention of K. Pneumoniae GI colonization, transmission, and infection. Successful commercialization would provide a profound front-line medical advancement in combating multidrug resistant klebsiella infection.