Understanding Anaplasmataceae pathogenesis using "Omics" approaches

Abstract

This paper examines how "Omics" approaches improve our understanding of Anaplasmataceae pathogenesis, through a global and integrative strategy to identify genes and proteins involved in biochemical pathways key for pathogen-host-vector interactions. The Anaplasmataceae family comprises obligate intracellular bacteria mainly transmitted by arthropods. These bacteria are responsible for major human and animal endemic and emerging infectious diseases with important economic and public health impacts. In order to improve disease control strategies, it is essential to better understand their pathogenesis. Our work focused on four Anaplasmataceae, which cause important animal, human and zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia chaffeensis, and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was also included in this review as a model of a non-pathogenic Anaplasmataceae. A gap analysis on "Omics" approaches on Anaplasmataceae was performed, which highlighted a lack of studies on the genes and proteins involved in the infection of hosts and vectors. Furthermore, most of the studies have been done on the pathogen itself, mainly on infectious free-living forms and rarely on intracellular forms. In order to perform a transcriptomic analysis of the intracellular stage of development, researchers developed methods to enrich bacterial transcripts from infected cells. These methods are described in this paper. Bacterial genes encoding outer membrane proteins, post-translational modifications, eukaryotic repeated motif proteins, proteins involved in osmotic and oxidative stress and hypothetical proteins have been identified to play a key role in Anaplasmataceae pathogenesis. Further investigations on the function of these outer membrane proteins and hypothetical proteins will be essential to confirm their role in the pathogenesis. Our work underlines the need for further studies in this domain and on host and vector responses to infection.

Keywords: Anaplasma; Anaplasmataceae; Ehrlichia; pathogenesis; proteomics; transcriptomics.

Figure 1

Intracellular life cycle of Anaplasmataceae. The Anaplasmataceae dense-cored cell develops into replicating reticulate cells in the phagosome, which does not fuse with lysosome and forms morulae (vegetative form). Then, reticulate cells mature into dense-cored cells that are liberated by exocytosis or host cell lysis (infectious form). Arrows, transition between stages; ER, endoplasmic reticulum.

Figure 2

Overview of pathogen, host, and vector transcriptomic and proteomic studies. Transcriptomic or proteomic studies done on host (pink circle) and on vector (blue circle) after pathogen infection (the name of the pathogen is indicated for each study). Transcriptomic or proteomic studies done on the pathogen (gray). Intersections of circles correspond to studies done both on the pathogen and on host or/and vector. In example, transcriptomic studies of Anaplasma phagocytophilum and of its host and vector have been done whereas only proteomic studies of Anaplasma phagocytophilum and its host have been performed.