New Study Unlocks Pathway To Thwart Flesh-Eating Bacteria
“Group A streptococcus infections are pretty widespread. Not only do they cause several million cases of strep throat every year, but also can lead to more severe infections, such as flesh-eating disease and acute rheumatic heart disease,” Muthiah Kumaraswami, Ph.D., an infectious diseases researcher at the Houston Methodist Research Institute, said. “If you don’t treat strep throat in children, for instance, recurring infections can lead to those more serious diseases and are very difficult to treat. We don’t have a vaccine, so basic research is geared toward finding targets for vaccine development.”
Successful pathogens use complex signaling mechanisms to monitor their environment and reprogram global gene expression during specific stages of infection. Group A Streptococcus (GAS) is a major human pathogen that causes significant disease burden worldwide. A secreted cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB) is a key virulence factor that is produced abundantly during infection and is critical for GAS pathogenesis. Although identified nearly a century ago, the molecular basis for growth phase control of speB gene expression remains unknown.
Scientists at the Houston Methodist Research Institute have now discovered that GAS uses a previously unknown peptide-mediated intercellular signaling system to control
SpeB production, alter global gene expression, and enhance virulence. By blocking the toxin, they may be able to prevent or treat the disease.The researchers believe that by manipulating the target, they can either reduce the severity of the infections or clear them up faster.
Kumaraswami says that bacteria talking to each other and producing toxins is not that new. Their communication codes have been characterized for a long time, so researchers know a lot of the classic features in these signals. What’s different in what his team discovered is the nature of the language. The Group A streptococcus communication signal they found lacks a majority of those classic hallmarks.
Moving forward, there are several different avenues researchers could take in targeting this peptide signal for either antibiotic or vaccine development. They can develop antibodies to target it or a competing peptide to jam the communication path, which would allow them to block toxin production and reduce disease severity. The second approach involves triggering the toxin production at the early stage where the toxin level would be minimal. Then, the host’s immune response would be triggered and clear the bacterial infection much earlier.
