Phenotypic and molecular characterization of polymyxin resistance in Salmonella spp. of animal origin

• Grant number: 21/12219-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: June 30, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Monique Ribeiro Tiba Casas
• Grantee: Monique Ribeiro Tiba Casas
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Carlos Henrique Camargo ; Enéas de Carvalho ; Marcos Paulo Vieira Cunha

Abstract

Approximately 700,000 people die each year from infections caused by resistant, multiresistant or even pan-resistant pathogens. The process of resistance to antimicrobials occurs naturally, however, the indiscriminate use of antibiotics in agriculture and in communities is becoming a threat to public health due to the inefficient action of drugs. Isolates of Salmonella spp. they are frequent causative agents of water and foodborne diseases, but they can also cause serious invasive diseases, especially in immunocompromised patients, and currently they have been showing resistance profiles to the main classes of antibiotics. In cases of multiresistant bacteria, it is necessary to search for a new therapeutic option, such as polymyxins. In 2015, the first report of polymyxin resistance mediated by the mcr gene (mobile colistin resistance) appeared, which spread across several continents. The objective of this work is to carry out the phenotypic and molecular characterization of Salmonella spp. resistant to polymyxins. The identification of the presence of mutations in genes associated with resistance to polymyxins (pmrA/B, phoP/Q) and plasmid resistance genes (mcr) to polymyxins will be carried out through PCR and Sanger sequencing. In colistin-resistant strains, the complete genome sequencing will be performed to characterize the plasmids of positive strains for the mcr genes that will be characterized against the molecular typing of plasmid incompatibility (Inc type) and pMLST. Through the results obtained from the sequencing, other associated resistance genes, virulence factors and genetic diversity through Core Genome Multilocus Sequence Typing (cgMLST) can be analyzed. Considering the representativeness and contemporaneity of the isolates received in our laboratory, from human, animal and environmental sources, we will carry out this study since data on resistance to polymyxins are still scarce in our country, and this drug is routinely used in animals causing selection pressure imposed by the use of colistin. Knowledge of the mechanisms of resistance to this drug could contribute to the understanding of the spread of resistance, and new control strategies could be implemented to limit the spread of resistance to this class of antimicrobial. (AU)