title: Genus-optimized strategy for the identification of chlamydial type III secretion substrates.
abstract: Among chlamydial virulence factors are the type III secretion (T3S) system and its effectors. T3S effectors target host proteins to benefit the infecting chlamydiae. The assortment of effectors, each with a unique function, varies between species. This variation likely contributes to differences in host specificity and disease severity. A dozen effectors of Chlamydia trachomatis have been identified; however, estimates suggest that more exist. A T3S prediction algorithm, SVM-based Identification and Evaluation of Virulence Effectors (SIEVE), along with a Yersinia surrogate secretion system helped to identify a new T3S substrate, CT082, which rather than functioning as an effector associates with the chlamydial envelope after secretion. SIEVE was modified to improve/expand effector predictions to include all sequenced genomes. Additional adjustments were made to the existing surrogate system whereby the N terminus of putative effectors was fused to a known effector lacking its own N terminus and was tested for secretion. Expansion of effector predictions by cSIEVE and modification of the surrogate system have also assisted in identifying a new T3S substrate from C. psittaci. The expanded predictions along with modifications to improve the surrogate secretion system have enhanced our ability to identify novel species-specific effectors, which upon characterization should provide insight into the unique pathogenic properties of each species.
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Hovis
authors.forename: Sergio
authors.initials: S
authors.lastname: Mojica
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Laura
authors.initials: L
authors.lastname: Pedersen
authors.forename: Chana
authors.initials: C
authors.lastname: Simhi
authors.forename: Roger G
authors.initials: RG
authors.lastname: Rank
authors.forename: Garry S A
authors.initials: GS
authors.lastname: Myers
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
authors.forename: Ru-ching
authors.initials: RC
authors.lastname: Hsia
authors.forename: Patrik M
authors.initials: PM
authors.lastname: Bavoil
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015870:Gene Expression; D023061:Gene Order; D006168:Guinea Pigs; D009154:Mutation; D021381:Protein Transport; D040901:Proteomics / Q000379:methods; D013045:Species Specificity; D013379:Substrate Specificity; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism
chemical_list: D058947:Bacterial Secretion Systems
keywords: Chlamydia; effector; type III secretion