title: Polymorphism of the Cysteine Protease YopT from Yersinia pestis.
abstract: Antibiotic therapy of plague is hampered by the recent isolation of Yersinia pestis strain resistant to all of antibiotics recommended for cure. This has constrained a quest for new antimicrobials taking aim at alternative targets. Recently Y. pestis cysteine protease YopT has been explored as a potential drug target. Targets conserved in the pathogen populations should be more efficacious; therefore, we evaluated intraspecies variability in yopT genes and their products. 114 Y. pestis isolates were screened. Only two YopT full-size isoforms were found among them. The endemic allele (N149) was present in biovar caucasica from Dagestan-highland natural plague focus # 39. The biovar caucasica strains from Transcaucasian highland (# 4-6) and Pre-Araks (# 7) plague foci also contained the N149 allele. These strains from foci # 4 7 possessed a truncated version of YopT that was a consequence of a frame-shift due to the deletion of a single nucleotide at position 71 bp. Computational analyses showed that although the SNP at the position 149 has a very minimal effect of the intrinsic disorder propensity of YopT proteins, whereas the N-terminal truncations of the YopT detected in bv. caucasica strains Pestoides F_YopT1 and F_YopT2, and Pestoides G generated isoforms with the significantly modified intrinsic disorder propensities and with reduced capability to interact with lost ability to utilize their N-terminal tail for the disorder-based interactions with biological partners. Considering that representatives of biovar caucasica were reported to be the reason of sporadic cases of human plague, this study supports the necessity of additional testing of globally disseminated YopT (S149) isoform as a potential target for treatment of plague caused by the strains producing different YopT isoforms.
authors: Mikhail E
authors: ME
authors: Platonov
authors: Tat'yana E
authors: TE
authors: Svetoch
authors: Vera V
authors: VV
authors: Evseeva
authors: Anastasiya I
authors: AI
authors: Knyazeva
authors: Svetlana V
authors: SV
authors: Dentovskaya
authors: Vladimir L
authors: VL
authors: Motin
authors: Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 07, Tampa, FL 33612, USA.. vuversky@health.usf.edu.
authors: Vladimir N
authors: VN
authors: Uversky
authors: State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Moscow Region, Russia.. a-p-anisimov@yandex.ru.
authors: Andrey P
authors: AP
authors: Anisimov
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000378:metabolism*; D010802:Phylogeny; D010930:Plague / Q000382:microbiology*; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D015010:Yersinia pestis / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D001426:Bacterial Proteins; D064267:Intrinsically Disordered Proteins; D020033:Protein Isoforms; C116117:YopT protein, Yersinia; D003546:Cysteine Endopeptidases