A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice
The development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient muta...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/6/953 |
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| author | Miriam Moscoso Juan A. Vallejo Maria P. Cabral Patricia García Víctor Fuentes-Valverde Eva Gato Jorge Arca-Suárez Pablo Aja-Macaya Germán Bou |
| author_facet | Miriam Moscoso Juan A. Vallejo Maria P. Cabral Patricia García Víctor Fuentes-Valverde Eva Gato Jorge Arca-Suárez Pablo Aja-Macaya Germán Bou |
| author_sort | Miriam Moscoso |
| collection | DOAJ |
| description | The development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient mutant, for preventing <i>Klebsiella pneumoniae</i> infections. The deletion mutant lacks the <i>murI</i> gene and requires exogenous addition of D-glutamate for growth. The results showed that the <i>K. pneumoniae</i> Δ<i>murI</i> strain is attenuated and includes a favourable combination of antigens for inducing a robust immune response and conferring an adequate level of cross-protection against systemic infections caused by <i>K. pneumoniae</i> strains, including some hypervirulent serotypes with elevated production of capsule polysaccharide as well as multiresistant <i>K. pneumoniae</i> strains. The auxotroph also induced specific production of IL-17A and IFN-γ. The rapid elimination of the strain from the blood of mice without causing disease suggests a high level of safety for administration as a vaccine. |
| first_indexed | 2024-03-09T22:16:13Z |
| format | Article |
| id | doaj.art-619c929ee0e945bfab10096283719a74 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:16:13Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-619c929ee0e945bfab10096283719a742023-11-23T19:22:00ZengMDPI AGVaccines2076-393X2022-06-0110695310.3390/vaccines10060953A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in MiceMiriam Moscoso0Juan A. Vallejo1Maria P. Cabral2Patricia García3Víctor Fuentes-Valverde4Eva Gato5Jorge Arca-Suárez6Pablo Aja-Macaya7Germán Bou8Department of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainDepartment of Microbiology, University Hospital A Coruña (CHUAC)—Biomedical Research Institute A Coruña (INIBIC), 15006 A Coruña, SpainThe development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient mutant, for preventing <i>Klebsiella pneumoniae</i> infections. The deletion mutant lacks the <i>murI</i> gene and requires exogenous addition of D-glutamate for growth. The results showed that the <i>K. pneumoniae</i> Δ<i>murI</i> strain is attenuated and includes a favourable combination of antigens for inducing a robust immune response and conferring an adequate level of cross-protection against systemic infections caused by <i>K. pneumoniae</i> strains, including some hypervirulent serotypes with elevated production of capsule polysaccharide as well as multiresistant <i>K. pneumoniae</i> strains. The auxotroph also induced specific production of IL-17A and IFN-γ. The rapid elimination of the strain from the blood of mice without causing disease suggests a high level of safety for administration as a vaccine.https://www.mdpi.com/2076-393X/10/6/953<i>Klebsiella pneumoniae</i>live vaccinesD-glutamate auxotrophyglutamate racemasecross-protection |
| spellingShingle | Miriam Moscoso Juan A. Vallejo Maria P. Cabral Patricia García Víctor Fuentes-Valverde Eva Gato Jorge Arca-Suárez Pablo Aja-Macaya Germán Bou A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice Vaccines <i>Klebsiella pneumoniae</i> live vaccines D-glutamate auxotrophy glutamate racemase cross-protection |
| title | A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice |
| title_full | A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice |
| title_fullStr | A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice |
| title_full_unstemmed | A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice |
| title_short | A New Live Auxotrophic Vaccine Induces Cross-Protection against <i>Klebsiella pneumoniae</i> Infections in Mice |
| title_sort | new live auxotrophic vaccine induces cross protection against i klebsiella pneumoniae i infections in mice |
| topic | <i>Klebsiella pneumoniae</i> live vaccines D-glutamate auxotrophy glutamate racemase cross-protection |
| url | https://www.mdpi.com/2076-393X/10/6/953 |
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