Abstract
The identification of bacterial effectors is essential to understand how obligatory intracellular bacteria such as Ehrlichia spp. manipulate the host cell for survival and replication. Infection of mammals–including humans–by the intracellular pathogenic bacteria Ehrlichia spp. depends largely on the injection of virulence proteins that hijack host cell processes. Several hypothetical virulence proteins have been identified in Ehrlichia spp., but one so far has been experimentally shown to translocate into host cells via the type IV secretion system. However, the current challenge is to identify most of the type IV effectors (T4Es) to fully understand their role in Ehrlichia spp. virulence and host adaptation. Here, we predict the T4E repertoires of four sequenced Ehrlichia spp. and four other Anaplasmataceae as comparative models (pathogenic Anaplasma spp. and Wolbachia endosymbiont) using previously developed S4TE 2.0 software. This analysis identified 579 predicted T4Es (228 pT4Es for Ehrlichia spp. only). The effector repertoires of Ehrlichia spp. overlapped, thereby defining a conserved core effectome of 92 predicted effectors shared by all strains. In addition, 69 species-specific T4Es were predicted with non-canonical GC% mostly in gene sparse regions of the genomes and we observed a bias in pT4Es according to host-specificity. We also identified new protein domain combinations, suggesting novel effector functions. This work presenting the predicted effector collection of Ehrlichia spp. can serve as a guide for future functional characterisation of effectors and design of alternative control strategies against these bacteria.
Highlights
Gram-negative intracellular bacteria Ehrlichia spp. are pathogens of eukaryotic cells
A fundamental step for the survival and replication of intravacuolar bacterial pathogens is the establishment of a replicative niche inside host cells by the secretion of bacterial effector proteins in the cytoplasm of the infected cells
E. chaffeensis, which is the agent of human monocytic ehrlichiosis, can cause disease in several other vertebrates, including dogs and deer [2] whereas E. canis, E. muris and E. ruminantium have narrower host ranges [3,4,5]
Summary
Gram-negative intracellular bacteria Ehrlichia spp. are pathogens of eukaryotic cells They have evolved to survive and replicate in a wide range of tick and mammalian hosts, including humans. In Gram-negative intracellular bacteria, a large number of effectors harbour eukaryotic-like domains [10] These proteins interfere in different steps of the infection by mimicking the functions of eukaryotic proteins [11,12]. A possible approach for the prediction of T4Es is the analysis of T4E protein sequences using machine learning [13] For this purpose, our laboratory developed the S4TE2.0 algorithm, which searches for a large number of motifs related to the function (eukaryotic-like domains, protein-protein interaction, etc.) and the subcellular location of predicted T4Es [14,15]
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