Deletion of Two Genes in Burkholderia pseudomallei MSHR668 That Target Essential Amino Acids Protect Acutely Infected BALB/c Mice and Promote Long Term Survival.

Autor:	Amemiya K; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Dankmeyer JL; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Biryukov SS; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Treviño SR; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Klimko CP; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Mou SM; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Fetterer DP; Biostatistical Services, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Garnes PG; Biostatistical Services, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Cote CK; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Worsham PL; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., DeShazer D; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2019 Nov 26; Vol. 7 (4). Date of Electronic Publication: 2019 Nov 26.
DOI:	10.3390/vaccines7040196
Abstrakt:	Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen Burkholderia pseudomallei . It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine against melioidosis. In this study, multiple B. pseudomallei MSHR668 deletion mutants were evaluated as live attenuated vaccines in the sensitive BALB/c mouse model of melioidosis. The most efficacious vaccines after an intraperitoneal challenge with 50-fold over the 50% median lethal dose (MLD 50 ) with B. pseudomallei K96243 were 668 Δ hisF and 668 Δ ilvI . Both vaccines completely protected mice in the acute phase of infection and showed significant protection (50% survivors) during the chronic phase of infection. The spleens of the survivors that were examined were sterile. Splenocytes from mice vaccinated with 668 Δ hisF and 668 Δ ilvI expressed higher amounts of IFN-γ after stimulation with B. pseudomallei antigens than splenocytes from mice vaccinated with less protective candidates. Finally, we demonstrate that 668 Δ hisF is nonlethal in immunocompromised NOD/SCID mice. Our results show that 668 Δ hisF and 668 Δ ilvI provide protective cell-mediated immune responses in the acute phase of infection and promote long term survival in the sensitive BALB/c mouse model of melioidosis.
Databáze:	MEDLINE
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