Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against <i>Yersinia pestis</i> Infection
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
Affiliations
Svetlana V. Dentovskaya
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Anastasia S. Vagaiskaya
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Mikhail E. Platonov
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Alexandra S. Trunyakova
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Sergei A. Kotov
Department of Disinfectology, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Ekaterina A. Krasil’nikova
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Galina M. Titareva
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Elizaveta M. Mazurina
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Tat’yana V. Gapel’chenkova
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Rima Z. Shaikhutdinova
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Sergei A. Ivanov
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Tat’yana I. Kombarova
Laboratory of Biomodels, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Vladimir N. Gerasimov
Department of Disinfectology, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
Vladimir N. Uversky
Department of Molecular Medicine and Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Andrey P. Anisimov
Laboratory for Plague Microbiology, Especially Dangerous Infections Department, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis 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 S and intact genes R-Rz 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 Y. pestis 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.
