Now, an international team led by Osaka University, Japan, in collaboration with Keio University, Japan, and University of California San Diego, USA, has discovered a way this disease organism obtains nutrition from the skin surface. This knowledge could lead to new therapeutic approaches to tackle infections. The team recently published the work inCell Reports.

It was already known that some bacteria break down arginine (an amino acid -- one of the building blocks of proteins) via a biochemical pathway named the arginine deaminase (ADI) pathway. The team confirmed thatS. pyogenescan survive using arginine even when starved of glucose. When they deleted the bacterial gene (namedarcA) encoding the first enzyme in the ADI pathway, theS. pyogeneslost that ability and also became less toxic towards human skin cells grown in culture.

When arginine is supplied, the ADI pathway ofS. pyogenesis activated but there are also widespread changes in gene expression. Some genes are down-regulated but large numbers of genes are up-regulated, including genes associated with virulence ofS. pyogenes, such as those that produce bacterial toxins.

Using mouse skin as a model system for human skin, the team showed for the first time thatS. pyogenescan use arginine to survive on the skin surface.S. pyogeneslacking thearcAgene survived poorly and were less virulent on mouse skin, confirming the importance of this pathway in the disease process. In contrast, in blood (containing plentiful glucose), the alteredS. pyogenesappeared no different to normalS. pyogenessince the ADI pathway was not needed.

"We showed that arginine from stratum corneum-derived filaggrin was a key substrate for the ADI pathway ofS. pyogenes," says lead researcher Dr. Yujiro Hirose. "In mice that do not produce filaggrin, less arginine is available and theS. pyogenesbacteria do not utilize ADI pathway to cause the skin lesion."

"This represents a significant step forward in understanding howS. pyogenessurvives on the skin," explains Dr. Hirose. "We expect our study will lead to novel treatment strategies: if we can block arginine metabolism inS. pyogenesit should restrict the pathogen's survival and virulence."