CAMBRIDGE, Mass. -- Scientists at Microbia, Inc. have identified a gene required by Staphylococcus aureus to mediate antibiotic resistance when forming biofilm colonies. The study is the first to find a link between the resistance mechanisms of biofilm bacteria and those present in methicillin-resistant S. aureus (MRSA), an increasing public health threat and the major cause of antibiotic failure in hospital-acquired infections. Microbia also announced the discovery of a new class of small-molecule compounds that increase the antibiotic sensitivity of S. aureus biofilms. Details were presented at the 42nd annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Diego.
"Microbia has identified a critical node in the network of genes that confer antibiotic resistance in Staphylococcus aureus biofilm infections, and we have the first compounds that target this network to restore antibiotic sensitivity," said Peter Hecht, PhD, CEO of Microbia. "These results underscore the promise of this approach to discovering new classes of anti-infectives that disable the intrinsic mechanisms of antibiotic resistance."
The team of researchers altered a conventional strain of S. aureus that is resistant to oxacillin in a biofilm by inactivating a single gene, which restored the efficacy of oxacillin against this mutant strain both in vitro and in vivo. This mutant is not affected in its sensitivity to antibiotics in the free-floating form as compared to wild type. The gene inactivated in this mutant, fmtC, was previously shown to play an important role in antibiotic resistance in MRSA. These data suggest that biofilm-mediated resistance and MRSA may have an unexpected overlap in molecular mechanisms of resistance. In addition, the investigative team discovered a novel class of compounds that restore oxacillin sensitivity of S. aureus biofilms.
S. aureus defies antibiotic treatment in a variety of clinical situations, and there is a growing body of evidence that S. aureus biofilms play a role in these treatment failures. Bacterial biofilms can be as much as 1,000-fold more resistant to antibiotics than the same free-floating bacteria. These bacterial biofilm infections affect approximately 10 million people in the U.S. every year. Conventional antibiotics may kill planktonic bacteria released by biofilms but do not eradicate the biofilm. Biofilms are commonly found on medical devices such as catheters, endotracheal tubes, and orthopedic implants, as well as surgical wound sutures. In addition to medical device infections, biofilms are implicated in serious systemic infections like cystic fibrosis, endocarditis and osteomyelitis.