Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection

To develop a modern plague vaccine, we used hypo-endotoxic <i>Yersinia</i> <i>pestis</i> bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the prot...

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Main Authors: Svetlana V. Dentovskaya, Anastasia S. Vagaiskaya, Mikhail E. Platonov, Alexandra S. Trunyakova, Sergei A. Kotov, Ekaterina A. Krasil’nikova, Galina M. Titareva, Elizaveta M. Mazurina, Tat’yana V. Gapel’chenkova, Rima Z. Shaikhutdinova, Sergei A. Ivanov, Tat’yana I. Kombarova, Vladimir N. Gerasimov, Vladimir N. Uversky, Andrey P. Anisimov
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/10/1/51
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author Svetlana V. Dentovskaya
Anastasia S. Vagaiskaya
Mikhail E. Platonov
Alexandra S. Trunyakova
Sergei A. Kotov
Ekaterina A. Krasil’nikova
Galina M. Titareva
Elizaveta M. Mazurina
Tat’yana V. Gapel’chenkova
Rima Z. Shaikhutdinova
Sergei A. Ivanov
Tat’yana I. Kombarova
Vladimir N. Gerasimov
Vladimir N. Uversky
Andrey P. Anisimov
author_facet Svetlana V. Dentovskaya
Anastasia S. Vagaiskaya
Mikhail E. Platonov
Alexandra S. Trunyakova
Sergei A. Kotov
Ekaterina A. Krasil’nikova
Galina M. Titareva
Elizaveta M. Mazurina
Tat’yana V. Gapel’chenkova
Rima Z. Shaikhutdinova
Sergei A. Ivanov
Tat’yana I. Kombarova
Vladimir N. Gerasimov
Vladimir N. Uversky
Andrey P. Anisimov
author_sort Svetlana V. Dentovskaya
collection DOAJ
description To develop a modern plague vaccine, we used hypo-endotoxic <i>Yersinia</i> <i>pestis</i> bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. A similar holin-endolysin system from phage λ containing mutated holin gene <i>S</i> and intact genes <i>R-Rz</i> coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type <i>Y. pestis</i> strain showed that bacterial envelopes protected only cavies. BGs with maximally hydrolyzed peptidoglycan had a greater protectivity compared to BGs with a preserved peptidoglycan skeleton.
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spelling doaj.art-916ac1aba06b4c579ead5362839655ce2023-11-23T15:38:32ZengMDPI AGVaccines2076-393X2021-12-011015110.3390/vaccines10010051Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> InfectionSvetlana V. Dentovskaya0Anastasia S. Vagaiskaya1Mikhail E. Platonov2Alexandra S. Trunyakova3Sergei A. Kotov4Ekaterina A. Krasil’nikova5Galina M. Titareva6Elizaveta M. Mazurina7Tat’yana V. Gapel’chenkova8Rima Z. Shaikhutdinova9Sergei A. Ivanov10Tat’yana I. Kombarova11Vladimir N. Gerasimov12Vladimir N. Uversky13Andrey P. Anisimov14Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaDepartment of Disinfectology, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaLaboratory of Biomodels, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaDepartment of Disinfectology, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaDepartment of Molecular Medicine and Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USALaboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaTo develop a modern plague vaccine, we used hypo-endotoxic <i>Yersinia</i> <i>pestis</i> bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. A similar holin-endolysin system from phage λ containing mutated holin gene <i>S</i> and intact genes <i>R-Rz</i> coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type <i>Y. pestis</i> strain showed that bacterial envelopes protected only cavies. BGs with maximally hydrolyzed peptidoglycan had a greater protectivity compared to BGs with a preserved peptidoglycan skeleton.https://www.mdpi.com/2076-393X/10/1/51<i>Yersinia pestis</i>vaccineguinea pigsbubonic plagueinactivated vaccinephage
spellingShingle Svetlana V. Dentovskaya
Anastasia S. Vagaiskaya
Mikhail E. Platonov
Alexandra S. Trunyakova
Sergei A. Kotov
Ekaterina A. Krasil’nikova
Galina M. Titareva
Elizaveta M. Mazurina
Tat’yana V. Gapel’chenkova
Rima Z. Shaikhutdinova
Sergei A. Ivanov
Tat’yana I. Kombarova
Vladimir N. Gerasimov
Vladimir N. Uversky
Andrey P. Anisimov
Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
Vaccines
<i>Yersinia pestis</i>
vaccine
guinea pigs
bubonic plague
inactivated vaccine
phage
title Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
title_full Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
title_fullStr Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
title_full_unstemmed Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
title_short Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
title_sort peptidoglycan free bacterial ghosts confer enhanced protection against i yersinia pestis i infection
topic <i>Yersinia pestis</i>
vaccine
guinea pigs
bubonic plague
inactivated vaccine
phage
url https://www.mdpi.com/2076-393X/10/1/51
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