Dataset Information

Affecting the Effectors: Regulation of Legionella pneumophila Effector Function by Metaeffectors.

ABSTRACT: Many bacterial pathogens utilize translocated virulence factors called effectors to successfully infect their host. Within the host cell, effector proteins facilitate pathogen replication through subversion of host cell targets and processes. Legionella pneumophila is a Gram-negative intracellular bacterial pathogen that relies on hundreds of translocated effectors to replicate within host phagocytes. Within this large arsenal of translocated effectors is a unique subset of effectors called metaeffectors, which target and regulate other effectors. At least one dozen metaeffectors are encoded by L. pneumophila; however, mechanisms by which they promote virulence are largely unknown. This review details current knowledge of L pneumophila metaeffector function, challenges associated with their identification, and potential avenues to reveal the contribution of metaeffectors to bacterial pathogenesis.

SUBMITTER: Joseph AM

PROVIDER: S-EPMC7911563 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Affecting the Effectors: Regulation of <i>Legionella pneumophila</i> Effector Function by Metaeffectors.

Joseph Ashley M AM Shames Stephanie R SR

Pathogens (Basel, Switzerland) 20210122 2

Many bacterial pathogens utilize translocated virulence factors called effectors to successfully infect their host. Within the host cell, effector proteins facilitate pathogen replication through subversion of host cell targets and processes. <i>Legionella pneumophila</i> is a Gram-negative intracellular bacterial pathogen that relies on hundreds of translocated effectors to replicate within host phagocytes. Within this large arsenal of translocated effectors is a unique subset of effectors call ...[more]

PMID: 33499048

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Project description:A large number of highly pathogenic bacteria utilize secretion systems to translocate effector proteins into host cells. Using these effectors, the bacteria subvert host cell processes during infection. Legionella pneumophila translocates effectors via the Icm/Dot type-IV secretion system and to date, approximately 100 effectors have been identified by various experimental and computational techniques. Effector identification is a critical first step towards the understanding of the pathogenesis system in L. pneumophila as well as in other bacterial pathogens. Here, we formulate the task of effector identification as a classification problem: each L. pneumophila open reading frame (ORF) was classified as either effector or not. We computationally defined a set of features that best distinguish effectors from non-effectors. These features cover a wide range of characteristics including taxonomical dispersion, regulatory data, genomic organization, similarity to eukaryotic proteomes and more. Machine learning algorithms utilizing these features were then applied to classify all the ORFs within the L. pneumophila genome. Using this approach we were able to predict and experimentally validate 40 new effectors, reaching a success rate of above 90%. Increasing the number of validated effectors to around 140, we were able to gain novel insights into their characteristics. Effectors were found to have low G+C content, supporting the hypothesis that a large number of effectors originate via horizontal gene transfer, probably from their protozoan host. In addition, effectors were found to cluster in specific genomic regions. Finally, we were able to provide a novel description of the C-terminal translocation signal required for effector translocation by the Icm/Dot secretion system. To conclude, we have discovered 40 novel L. pneumophila effectors, predicted over a hundred additional highly probable effectors, and shown the applicability of machine learning algorithms for the identification and characterization of bacterial pathogenesis determinants.

Dataset Information

Affecting the Effectors: Regulation of Legionella pneumophila Effector Function by Metaeffectors.

Publications

Affecting the Effectors: Regulation of <i>Legionella pneumophila</i> Effector Function by Metaeffectors.

Similar Datasets

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