The discovery and therapeutic application of naturally occurring antibiotics has saved many lives, however their overuse has also hastened the emergence of antibiotic resistant pathogens. Naturally occurring antibiotics are broad spectrum for good biological reasons, targeting whole classes of bacteria. In response, bacteria have evolved to easily share antibiotic-resistance genes among themselves. The widespread therapeutic introduction of these broad spectrum antibiotics into the medical and general environment killed many non-pathogens, upsetting ecological balances and our own microbiome, and favoring the development and spread of drug-resistant pathogen strains. Beyond managing these broad spectrum antibiotics more intelligently, new approaches are needed.
To address this growing challenge, the precision medicine paradigm is being applied to antibacterial agents. AvidBiotics is developing new antibacterial drugs that target the bacterial pathogen, sparing benign and useful bacteria and circumventing the acquisition of resistance from other microbes. Rapid gene sequencing and other recent advances enable diagnostics for fast, accurate identification of disease-causing bacteria and their particular drug sensitivities. A new class of bactericidal proteins is thereby being developed, engineered to kill precisely targeted bacteria without damaging the diversity of healthy microbiota of the host. These agents, Avidocin proteins, are orally active in the gut of experimental animals. Capable of subtracting selected bacterial species, they can prevent or treat enteric bacterial diseases. One such example is Avidocin-CD, which potently kills the epidemic strains of Clostridium difficile and in animal models can prevent C. difficile infections, now the most common hospital-acquired infection in the US. Use of this precision medicine approach to develop a portfolio of Avidocin agents for human and animal health as well as food safety applications will be discussed.
David W. Martin, Jr., M.D., is Chairman & CEO of AvidBiotics Corp., a biotechnology company in South San Francisco focused on preventing and treating bacterial diseases. He co-founded and was CEO of Eos Biotechnology, President of Chiron Therapeutics (1994-1995), and Executive Vice-President of R&D at DuPont Merck (1991-1993).
Prior to joining Genentech where he was Senior Vice-president of R&D (1982-1990), he was Professor of Medicine and Biochemistry at UCSF and Investigator, Howard Hughes Medical Institute. He attended M.I.T. and received his M.D. from Duke University