The study shows that a bacterial enzyme (ApdS) from Streptococcus suis can cut up the human antimicrobial peptide LL‑37, making it less able to kill the bacteria and to activate immune cells. When the bacteria encounter LL‑37, they produce more of this enzyme, which helps them evade the body's first line of defense.

<i>Streptococcus suis</i> is a globally distributed zoonotic pathogen associated with meningitis and septicemia in humans, posing a serious threat to public health. To successfully invade and disseminate within its host, this bacterium must overcome the innate immune system. The antimicrobial peptide LL-37 impedes invading pathogens by directly perforating bacterial membranes and stimulating the immune function of neutrophils, which are the major effector cells against <i>S. suis</i> However, little is known about the biological relationship between <i>S. suis</i> and LL-37 and how this bacterium adapts to and evades LL-37-mediated immune responses. In this study by using an array of approaches, including enzyme, chemotaxis, cytokine assays, quantitative RT-PCR, and CD spectroscopy, we found that the cysteine protease ApdS from <i>S. suis</i> cleaves LL-37 and thereby plays a key role in the interaction between <i>S. suis</i> and human neutrophils. <i>S. suis</i> infection stimulated LL-37 production in human neutrophils, and <i>S. suis</i> exposure to LL-37 up-regulated ApdS protease expression in the bacterium. We observed that ApdS targets and rapidly cleaves LL-37, impairing its bactericidal activity against <i>S. suis</i> We attributed this effect to the decreased helical content of the secondary structure in the truncated peptide. Moreover, ApdS rescued <i>S. suis</i> from killing by human neutrophils and neutrophil extracellular traps because LL-37 truncation attenuated neutrophil chemotaxis and inhibited the formation of extracellular traps and the production of reactive oxygen species. Altogether, our findings reveal an immunosuppressive strategy of <i>S. suis</i> whereby the bacterium blunts the innate host defenses via ApdS protease-mediated LL-37 cleavage.