Targeting autolysin ATL of Streptococcus suis: structural insights and inhibition by lanreotide acetate

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe infections in pigs and humans. Bacterial autolysins play essential roles in cell-wall remodelling and virulence; however, the structural and functional characteristics of the SS2 autolysin ATL remain poorly understood. With the increasing emergence of antimicrobial resistance, anti-virulence strategies that attenuate bacterial pathogenicity without directly inhibiting growth have attracted increasing attention.

ATL domain organization was analysed bioinformatically. The catalytic domain was expressed, purified and crystallized, and its structure was determined at 1.8 Å resolution. An atl deletion mutant was generated, and ATL function was evaluated by autolysis, biofilm formation, adhesion and mouse infection assays. Lanreotide acetate was assessed for its effects on bacterial growth, ATL inhibition and anti-virulence activity in vitro and in vivo.

ATL contains cell-wall-binding repeats and a C-terminal Zn2+-dependent amidase domain with a His13-Glu27-His81 catalytic site. Deletion of atl did not affect bacterial growth but reduced autolysis, biofilm formation, adhesion and virulence in mice. Lanreotide acetate had a minimum inhibitory concentration (MIC) of 512 mg/L and showed no growth inhibition at sub-MIC concentrations. However, it inhibited ATL activity and reduced autolysis, biofilm formation, adhesion, barrier penetration and bacterial burden, while alleviating splenic pathology.

ATL is a key SS2 virulence-associated autolysin. Lanreotide acetate attenuates SS2 pathogenicity by inhibiting ATL activity without suppressing bacterial growth, supporting ATL as a potential anti-virulence target.