|
Methicillin resistant Staph aureus (MRSA) have become increasingly unresponsive to first-line antibiotic therapy and have compromised the utility of methicillin and related antibiotics, cephalosporins, macrolides, quinolones, and beta-lactamase inhibitors. Even the last drug of choice, vancomycin, is often ineffective in eradicating serious MRSA infections.
Scientists at UCSD have discovered a new target which may provide an entirely new class of antibiotics for treating MRSA. Using a molecular genetic approach pairing mutagenesis and heterologous expression, the researchers have been able to identify the virulence factor of S. aureus. The factor, which is normally present in the organism, was shown to protect the organism from host peroxide and renders it more resistant to phagocytic killing. Inhibition of the factor rendered the organisms more susceptible to oxidants and impaired in blood survival. To assess the significance of the factor in disease pathogenesis, organisms without the factor were evaluated in murine subcutaneous challenge models of infection, and were not able to generate infection. In other studies, agents that inhibit the factor were shown to inhibit the virulence of the organisms in a dose-dependent fashion.
National prospective surveillance of over 24,000 invasive bacterial isolates show disease-associated S. aureus strains with methicillin resistance have increased from 22% in 1995 to 57% currently. An urgent need exists for discovery of novel classes of antibiotics to address this public health crisis. The approach presented here may provide a novel target for a new class of antibiotics.
Case No: SD2005-166
Inquiries To: invent@ucsd.edu
|
