Salmonella Gallinarum mgtC mutant shows a delayed fowl typhoid progression in chicken

• Published in: Gene 2024-01, Vol.892, p.147827-147827, Article 147827
• Main Authors: Rodrigues Alves, Lucas Bocchini, Freitas Neto, Oliveiro Caetano de, Saraiva, Mauro de Mesquita Souza, do Monte, Daniel Farias Marinho, de Lima, Bruna Nestlehner, Cabrera, Julia Memrava, Barbosa, Fernanda de Oliveira, Benevides, Valdinete Pereira, de Lima, Túlio Spina, Campos, Isabella Cardeal, Rubio, Marcela da Silva, Nascimento, Camila de Fatima, Arantes, Letícia Cury Rocha Veloso, Alves, Victória Veiga, de Almeida, Adriana Maria, Olsen, John Elmerdahl, Berchieri Junior, Angelo
• Format: Article
• Language: English
• Subjects: bacteria; chickens; disease course; disease progression; Fowl typhoid; gene expression; genes; immunohistochemistry; infectious diseases; interleukins; liver; Macrophages; mortality; mutants; Pathogenesis; pathogenicity; pathogenicity islands; pathogens; Salmonella Gallinarum; Salmonellosis; serotypes; SPI-3; spleen; Systemic infection
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2023.147827

Salmonella Gallinarum (SG) provokes fowl typhoid, an infectious disease of acute clinical course that affects gallinaceous of any age and leads to high mortality rates. During the typhoid-like systemic infection of S. Typhimurium (STM) in mice, the bacterium expresses the mgtC gene, which is encoded in the Salmonella Pathogenecity Island – 3 (SPI-3). In this serovar, the function is linked to bacterial replication within macrophages, and its absence attenuates the pathogen. We hypothesized that deleting mgtC from SG genome would alter the microorganism pathogenicity in susceptible commercial poultry in a similar manner. Thus, the present study sought to elucidate the importance of mgtC on SG pathogenicity. For this, a mgtC-mutant lacking S. Gallinarum mutant was constructed (SG ΔmgtC). Its ability to replicate in medium that mimicries the mgtC-related intracellular environment of macrophages as well as in primary macrophages from chicken was evaluated. Moreover, the infection of susceptible chickens was performed to elucidate its pathogenicity and the elicited immune responses by measuring key interleukins by qRT-PCR and the population of macrophages and lymphocytes T CD4+ and CD8+ by means of immunohistochemistry. It was observed that mgtC was required for S. Gallinarum replication in acidified low-Mg2+ media and survival within macrophages. However, unlike its requirement for initial phase of STM infection in mice, lower bacterial counts were only observed at the late stage of macrophage infection without affecting the citotoxicity. Experiments showed that knocking-out the mgtC gene neither altered bacterial uptake by macrophages nor affects bacterial counts in liver and spleen and total chicken mortality. However, plotting a survival curve and analyzing the clinical-pathologic conditions, it was observed a slower progression of the disease in chickens infected by SG ΔmgtC compared to those challenged by the wild-type strain. Furthermore, the mRNA expression of IFN-γ and LITAF were similar between the infected chickens, but higher than in the uninfected group. The same was observed in macrophages and lymphocytes T CD4+ populations. On the other hand, the presence of lymphocytes T CD8+ was increased in the initial phase of the disease provoked by the wild-type strain over the mutant strain. We concluded that the role of mgtC in Fowl Typhoid in susceptible chickens differs from the role in typhoid-like infections in mammals. Thus, the deletion of mgtC gene