Huntsville, Ala. — 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.
AboutiXpressGenes: iXpressGenes is a synthetic biology company located at the HudsonAlpha Institute for Biotechnology. Our company specializes in protein services and instrumentation, and drug discovery research. We support commercial, institutional and academic organizations. We have a special background in extremozymes, microgravity and trace fluorescent labeling. iXpressGenes has exclusive access to a suite of hyperthermophilic genomes from the deep sea vents of the Atlantic Ridge. Proteins and enzymes from these genomes have special qualities that are useful in engineering and metabolic reactions. Our team has deep experience in microgravity, having conducted several experiments on the International Space Station. These experiments have led us to diffraction studies in both X ray and neutron beam. Years of research in protein crystallization led us to a new technique that is highly effective in finding and discerning leads – trace fluorescent labeling. Our disciplines are in biochemistry, structural genomics and instrumentation.
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to innovating in the field of genomic technology and sciences across a spectrum of biological challenges. Opened in 2008, its mission is four-fold: sparking scientific discoveries that can impact human health and well-being; bringing genomic medicine into clinical care; fostering life sciences entrepreneurship and business growth; and encouraging the creation of a genomics-literate workforce and society. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. Designed to be a hothouse of biotech economic development, HudsonAlpha’s state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. The relationships formed on the HudsonAlpha campus encourage collaborations that produce advances in medicine and agriculture. Under the leadership of Dr. Richard M. Myers, a key collaborator on the Human Genome Project, HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education and includes more than 30 diverse biotech companies on campus. To learn more about HudsonAlpha, visit: www.hudsonalpha.org.