New Drugs Diminish Group A Streptococcus Pathogenicity

A new category of drugs was found to be effective in protecting mice from infection by group A streptococcus (GAS) bacteria.

Drug developers have been searching for replacements to currently used antibiotics that would lower the chances that the target bacteria would evolve mechanisms of resistance to the drugs. One approach that may minimize selection for resistant organisms is to direct the drugs at molecules involved in microbial pathogenicity without inhibiting bacterial growth.

Toward this end, investigators at the University of Missouri (Columbia, USA) and University of Michigan (Ann Arbor, USA) looked for compounds capable of inhibiting gene expression of streptokinase (SK), a critical group A streptococcal (GAS) virulence factor.

The Investigators reported in the February 13, 2012, online edition of the journal Proceedings of the [US] National Academy of Sciences that during a high-throughput, growth-based screen of a library of 55,000 small molecules, they had identified the compound CCG-2979 and an analog CCG-102487 that inhibited the production of active SK protein. Microarray analysis of GAS grown in the presence of CCG-102487 showed down-regulation of a number of important virulence factors in addition to SK, suggesting disruption of a general virulence gene regulatory network. CCG-2979 and CCG-102487 both enhanced granulocyte phagocytosis and killing of GAS in an in vitro assay, and CCG-2979 also protected mice from GAS-induced mortality in vivo.

“We know that 70% of bacteria causing infections in the hospital are resistant to at least one of the drugs commonly used for treatment,” said first author Dr. Hongmin Sun, assistant professor of internal medicine at the University of Missouri. “Rather than killing off the bacteria, this new compound changes the behavior of the bacteria and makes it less harmful.”

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