Impact of cathelicidin cleavage by SpeB on Streptococcus pyogenes CovRS signaling

Guerra, S.; Qu, C.; LaRock, C.

doi:10.64898/2026.08.12.744433

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bioRxiv · 10.64898/2026.08.12.744433

Impact of cathelicidin cleavage by SpeB on Streptococcus pyogenes CovRS signaling

Guerra, S.·Qu, C.·LaRock, C.

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Abstract

Cathelicidins are a class of antimicrobial peptides (AMPs) that are part of the first line of defense of the innate immune system. While cathelicidin-derived peptides such as LL-37 can be directly bactericidal, Streptococcus pyogenes (Spy; Group A Streptococcus) is highly resistant to killing. Furthermore, Spy detects LL-37 through the CovRS two-component system to regulate its virulence factors. One effect of this signaling is the repression of expression of the bacterial protease SpeB. Prior work has also shown that SpeB, along with other bacterial proteases can cleave LL-37. However, it is unclear if SpeB cleavage of LL-37 impacts antimicrobial function and CovRS signaling activity. Using a genetic approach, we show that the presence SpeB did not significantly impact the killing of Spy by LL-37 relative to other known resistance factors. Furthermore, while SpeB cleaves LL-37, CovRS maintains sensitivity to LL-37 fragments. These results indicate that SpeB cleavage of LL-37 does not negatively impact virulence factor regulation in Spy.

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Guerra, S., Qu, C., LaRock, C.. 2026-08-12. Impact of cathelicidin cleavage by SpeB on Streptococcus pyogenes CovRS signaling. https://doi.org/10.64898/2026.08.12.744433

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