Daniel Williams
Dec 17, 2024
iXpressGenes (iXG) has been awarded a $1,000,000 Phase II Department of Defense (DoD) Small Business Innovation contract to develop extremophile-derived antibiotics to protect soldiers from biowarfare agents and “superbugs.” Selection was based on achievements during the Phase I project to now continue development and maturation of discovered antibiotic candidates.
iXG, a biotechnology company located on the HudsonAlpha Institute for Biotechnology campus, specializes in protein crystallization, microbiome and structure-based drug discovery.
iXG has developed a rare environmental DNA library from extremophilic environmental samples, collected from hot springs, thermal vents, and permafrost. Extremophilic organisms are those that thrive in extreme physical or chemical conditions that are hostile to most life on earth. Using next generation sequencing technology and bioinformatics tools, researchers discovered a high prevalence (>60%) of novel organisms and biosynthetic pathway types within environmental DNA samples from extreme cold (permafrost) and hot (hot springs) environments. A high throughput platform, Extremophilic Microbiome Antimicrobial Discovery (EMAD), was created during the Phase I effort.
“We believe our EMAD platform provides the optimal path to combating antimicrobial resistant (AMR) bacteria by rapidly discovering drug-like, antibacterial compounds with high rates of novel chemistry due to their extremophilic origins,” said AJ Singhal, the principal investigator and iXG Director of Drug Discovery. “These new chemical classes will produce desperately needed novel mechanism of action antibiotics, which can circumvent all current resistance mechanisms.”
The EMAD platform has three major advantages over the current state-of-the-art: 1) the understudied extremophilic sources greatly reduce rediscovery of known compounds which plague other platforms; 2) the source also provides high degrees of novel chemistry, which greatly increase new antibiotic mechanism of action discovery rates; and 3) the engineered bacterial host selects for drug-like compounds, which also enhances the efficiency of the discovery process.
Six novel, broad-spectrum antibacterial natural product extracts were discovered during the Phase I effort. Sequencing and bioinformatics analysis of these six antibiotic-producing clones indicates natural products with novel chemistry. Novel chemical class antibiotics are desperately needed to combat the growing antimicrobial resistance (AMR) crisis.
AMR pathogens kill approximately 700,000 people per year globally. iXG President Joe Ng, Ph.D., is pleased to see some promising antibacterial extracts resulting from early and recent explorations made by himself, Owen Garriott and Richard Garriott while seeking out novel organisms, “Nature has long been the best provider of antimicrobials, we’re happy to expand the field by harnessing the full potential of understudied extremophilic microbiomes with our unique platform.”
These novel compounds will be further characterized and tested against DoD priority pathogens by collaborators Blaine Pfeifer, Ph.D. (SUNY Buffalo), Mark Liles, Ph.D. (Auburn University), USAMRIID, and HudsonAlpha associate companies Serina Therapeutics and CFD Research Corporation during the Phase II project.
