title: Secretome of obligate intracellular Rickettsia.
abstract: The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g. josamycin, ciprofloxacin, chloramphenicol, and azithromycin) are also effective. Much of the recent research geared toward understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial 'life on the inside'.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA jgillespie@som.umaryland.edu.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Gillespie
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Simran J
authors.initials: SJ
authors.lastname: Kaur
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: M Sayeedur
authors.initials: MS
authors.lastname: Rahman
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Rennoll-Bankert
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Khandra T
authors.initials: KT
authors.lastname: Sears
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Magda
authors.initials: M
authors.lastname: Beier-Sexton
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Abdu F
authors.initials: AF
authors.lastname: Azad
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D019295:Computational Biology; D005057:Eukaryotic Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D042541:Intracellular Space / Q000382:microbiology*; D012281:Rickettsia / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins
keywords: Sec translocon; Sec-TolC pathway; T1SS; T4SS; T5SS; Tat system