RESUMEN
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.
Asunto(s)
Proteínas Bacterianas/genética , Cisteína Endopeptidasas/genética , Proteínas Intrínsecamente Desordenadas/metabolismo , Peste/microbiología , Polimorfismo de Nucleótido Simple , Yersinia pestis/aislamiento & purificación , Alelos , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Sitios de Unión , Biología Computacional/métodos , Cisteína Endopeptidasas/química , Humanos , Filogenia , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Yersinia pestis/clasificación , Yersinia pestis/genéticaRESUMEN
We report the first draft genome sequences of two Yersinia pseudotuberculosis sequence type 43 (ST43) (O:1b) strains, B-7194 and B-7195, isolated in Russia. The total lengths of the assemblies are 4,427,121 bp and 4,608,472 bp, and 3,819 and 4,018 coding sequences, respectively, were predicted within the genomes.
RESUMEN
We report the first draft genome sequences of five Yersinia pseudotuberculosis isolates of sequence type (ST) 19 and of a variant from one of the five isolates. The total length of assemblies ranged from 4,226,485 bp to 4,274,148 bp, including between 3,808 and 3,843 predicted coding sequences.
