A survey of ADP-ribosyltransferase families in the pathogenic Legionella

Abstract

BackgroundADP-ribosyltransferases (ARTs) are a superfamily of enzymes implicated in various cellular processes, including pathogenic mechanisms. The Legionella genus, known for causing Legionnaires disease, possesses diverse ART-like effectors. This study explores the proteomes of 41 Legionella species to bioinformatically identify and characterise novel ART-like families, providing insights into their potential roles in pathogenesis and host interactions. MethodsWe conducted a comprehensive bioinformatic survey of 41 Legionella species to identify proteins with significant sequence or structural similarity to known ARTs. Sensitive sequence searches were performed to detect candidate ART-like families. Subsequent validation, including structure prediction of such families, was achieved using artificial intelligence-driven tools, such as AlphaFold. Comparative analyses were performed to assess sequence and structural similarities between the novel ART-like families and known ARTs. ResultsOur analysis identified 63 proteins with convincing similarity to ARTs, organised into 39 ART-like families, including 26 novel families. Key findings include: O_LIDUF2971 family: exhibits sequence similarity to DarT toxins and other DNA-acting ARTs. C_LIO_LIDUF4291 family: the largest newly identified family shows structural and sequence similarity to the diphtheria toxin, suggesting the ability to modify proteins. C_LI Most members of the novel ART families are predicted effectors. Although experimental validation of the predicted ART effector functions is necessary, the novel ART-like families identified present promising targets for understanding Legionella pathogenicity and developing therapeutic strategies. We publish a complete catalogue of our results in the astARTe database: http://bioinfo.sggw.edu.pl/astarte/.