HU-Lacking Mutants of Salmonella enterica Enteritidis Are Highly Attenuated and Can Induce Protection in Murine Model of Infection

Autor(es)

Milanez, Guilherme P. ^[1] ; Werle, Catierine H. ^[1] ; Amorim, Mariene R. ^[1] ; Ribeiro, Rafael A. ^[1] ; Tibo, Luiz H. S. ^[1] ; Roque-Barreira, Maria Cristina ^[2] ; Oliveira, Aline F. ^[2] ; Brocchi, Marcelo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, SP - Brazil

^[2] Univ Sao Paulo, Dept Cellular & Mol Biol, Fac Med Ribeirao Preto, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 9, AUG 22 2018.
• Citações Web of Science: 0

Resumo

Salmonella enterica infection is a major public health concern worldwide, particularly when associated with other medical conditions. The serovars Typhimurium and Enteritidis are frequently associated with an invasive illness that primarily affects immunocompromised adults and children with HIV, malaria, or malnutrition. These serovars can also cause infections in a variety of animal hosts, and they are the most common isolates in poultry materials. Here, we described S. Enteritidis mutants, where hupA and hupB genes were deleted, and evaluated their potential use as liveattenuated vaccine candidates. In vitro, the mutants behaved like S. Typhimurium described previously, but there were some particularities in macrophage invasion and survival experiments. The virulence and immunogenicity of the mutant lacking both hupA and hupB (PT4 Delta hupAB) were evaluated in a BALB/c mice model. This mutant was highly attenuated and could, therefore, be administrated at doses higher than 10(9) CFU/treatment, which was sufficient to protect all treated mice challenged with the wild-type parental strain with a single dose. Additionally, the PT4 Delta hupAB strain induced production of specific IgG and IgA antibodies against Salmonella and TH1-related cytokines (IFN-gamma and TNE-alpha), indicating that this strain can induce systemic and mucosal protection in the murine model. Additional studies are needed to better understand the mechanisms that lead to attenuation of the double-mutant PT4 Delta hupAB and to elucidate the immune response induced by immunization using this strain. However, our data allow us to state that hupAB mutants could be potential candidates to be explore as live-attenuated vaccines. (AU)

• Processo FAPESP: 13/04088-0 - Lectinas de patógenos
• Beneficiário: Maria Cristina Roque Antunes Barreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/57354-0 - Avaliação do potencial imunogênico e protetor de novas linhagens atenuadas de Salmonella enterica Typhimurium
• Beneficiário: Aline Ferreira de Oliveira Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/05382-6 - Avaliação da virulência e expressão gênica diferencial in vivo de Salmonella enterica mutantes para proteínas associadas ao nucleóide.
• Beneficiário: Guilherme Paier Milanez
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/13412-8 - Salmonella enterica: importância de NAPS na patogenicidade e atenuação da virulência
• Beneficiário: Marcelo Brocchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/05359-0 - Distribuição de paracoccina na superfície de Paracoccidioides brasiliensis e interação com receptores de células da imunidade inata: papel na fase aguda da paracoccidioidomicose
• Beneficiário: Aline Ferreira de Oliveira Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado