Intercellular peptide identified as a potential therapeutic target in group A Streptococcus

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New research has uncovered a leaderless intercellular peptide signal that might contribute to the mechanisms behind group A Streptococcus (GAS) virulence, providing a framework to investigate these signals in other bacteria.

GAS can causes an array of symptoms including mild pharyngitis and necrotizing fasciitis. GAS produces many bacterial virulence factors, including streptococcal pyrogenic exotoxin B (SpeB). In infected humans, SpeB is produced abundantly and is crucial for the development of necrotizing fasciitis.

Muthiah Kumaraswami (Houston Methodist, TX, USA), one of the authors of the study that was published in Proceedings of the National Academy of Sciences, explained: “GAS 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… If you don’t treat strep throat in children, for instance, recurring infections can lead to those more serious diseases [necrotizing fasciitis and acute rheumatic heart disease]and are very difficult to treat. We don’t have a vaccine, so basic research is geared toward finding targets for vaccine development.”

Although SpeB was identified almost a century ago, researchers haven’t been able to detect what initiates SpeB production by GAS. Bacterial production of toxins and cell communication codes have been characterized previously, however, the researchers were able to find that the GAS communication signal lacks a majority of the classic hallmarks found in typical signalling pathways.

“Typically, the signal is quite long and has a number of characteristic features,” Kumaraswami commented. “The signal we found is compact and doesn’t have many of what we traditionally see in other bacterial peptides, which is probably what contributed to the difficulties in finding it for such a long time. There could be similar atypical signals in other bacteria that have been overlooked, as well, so we believe the discovery of this peptide will likely facilitate discovering additional bacterial peptide signals in other pathogens.”

The researchers identified a previously unknown peptide-mediated intercellular signalling system to control SpeB production, which they referred to as SIP. Within their study, they went into further detail about the mechanism by which SIP induces SpeB production and its contribution to GAS virulence.

This discovery of SIP provides a framework for the identification of other SIP-like leaderless peptides in other microorganisms. The researchers concluded that: “Our data reveal a paradigm of bacterial signalling and identify previously unknown molecules that may serve as therapeutic targets.”

Sources: Do H, Makthal N, VanderWal AR et al. Leaderless secreted peptide signaling molecule alters global gene expression and increases virulence of a human bacterial pathogen. Proc. Natl Acad. Sci. USA doi:10.1073/pnas.1705972114 (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-09/hm-rup091817.php

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