Thymine- and thymidine-dependent mutants of Y. pestis strain EV-76 have been isolated and characterized. Obtaining Y. pestis thymine-dependent mutants in trimethoprim-containing media with full nutritional value in the presence of thymine and thymidine and the capacity of natural strains from the foci of infection in Transcaucasia and Mongolia to grow in such media indicate that Y. pestis has gene tpp controlling thymidine phosphorylase, but this enzyme is strongly suppressed under normal conditions. The capacity for its suppression under definite conditions and the degree of the activation of thymidine phosphorylase determine the realization of Thy and Thyd phenotypes in Y. pestis mutants under study, though both types of these mutants have a mutation damage of gene thy A coding the synthesis of thymidylate synthetase.
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bioRxiv
December 2024
Department of Microbiology and Immunology, University of Louisville.
is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signaling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation.
View Article and Find Full Text PDFTwo live attenuated vaccines (LAVs), LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their efficacy and immune responses in wild type (WT) and interferon gamma (IFNγ) knockout (KO) mice in a C57BL/6 background. While LMA and LMP are triple deletion mutants of CO92 strain, Ad5-YFV incorporates three protective plague immunogens. An impressive 80-100% protection was observed in all vaccinated animals against highly lethal intranasal challenge doses of parental CO92.
View Article and Find Full Text PDFPLoS Pathog
October 2024
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Leukotriene B4 (LTB4) is an inflammatory lipid produced in response to pathogens that is critical for initiating the inflammatory cascade needed to control infection. However, during plague, Yersinia pestis inhibits the timely synthesis of LTB4 and subsequent inflammation. Using bacterial mutants, we previously determined that Y.
View Article and Find Full Text PDFComb Chem High Throughput Screen
August 2024
Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, India.
mSphere
September 2024
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA-F1V, respectively. We show that OmpA-ls-F1V and OmpA-F1V can be successfully delivered into the lumen and membrane of the OMVs of respectively.
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