Heterogeneity in ¿-lactam resistance confered by a mobile element

• Grant number: 24/23910-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo da Silva Galhardo
• Grantee: Caiani Dutra Alves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

Antibiotic resistance in bacteria is one of the greatest threats to global public health, and the spread of resistance genes, such as those encoding ¿-lactamases, has complicated the treatment of severe infections. Among these enzymes, CMY-2, an AmpC-type ¿-lactamase present in plasmids, has stood out for conferring resistance to broad-spectrum cephalosporins and other ¿-lactams. Recently, an integrative conjugative element (ICE), ICEPmiJpn1, carrying the blaCMY-2 gene, was identified in Proteus mirabilis. This ICE, belonging to the SXT/R391 family, plays a crucial role in spreading resistance among different bacterial strains and species. However, preliminary studies suggest that the manifestation of the resistance phenotype in P. mirabilis and Escherichia coli carrying ICEPmiJpn1 is heterogeneous, meaning that the expression of ampicillin resistance does not occur uniformly across all cells in the population. This phenomenon suggests that the regulation of blaCMY-2 expression may be more complex than previously thought, potentially influenced by the structure of the ICE and contextual factors, such as the presence of other genes associated with a transposon carrying blaCMY-2. Given the impact of antimicrobial resistance on public health and the relevance of the CMY-2 enzyme in the spread of this resistance, this project aims to investigate the underlying mechanisms of phenotypic heterogeneity in ¿-lactam resistance conferred by a mobile element