Genomic and phenotypic characterization of hospital and community-acquired Methicillin-Resistant Staphylococcus aureus (MRSA) search for new antibacterial agents

Abstract

Staphylococcus aureus, a Gram-positive pathogen that can exhibit multidrug resistance, is responsible for both hospital-acquired and community-based infections and is seen as a leading cause of morbidity and mortality worldwide. Methicillin-resistant S. aureus (MRSA) is considered a serious threat by the CDC, accounting for 23% of S. aureus infection cases in 2018, according to BrGLASS. The formation of MRSA occurs through the incorporation of the staphylococcal chromosomal cassette mec (SCCmec), a genomic island that encodes mecA or mecC and confers resistance to most ²-lactams. Fifteen SCCmec (I-XV) types have already been identified, and their prevalence varies geographically depending on their adaptation. This study will analyze current MRSA strains from outpatients and hospitalized patients in São Luís (MA) and São Carlos (SP). The antimicrobial sensitivity profile will be determined, and clones will be selected by PFGE typing to sequence genomes by Illumina and Nanopore that can reveal circulating lineages and new genetic elements of resistance/virulence. Given the scarcity of therapeutic options for this pathogen, we will test new antimicrobial peptides (AMPs), which stand out as an attractive study option due to their wide diversity and spectrum of activity. We will prospect bacteriophages, which are more species and lineage-specific, for further studies. Among the AMPs studied, those with the best activity will be selected for testing with different strains of MRSA, including those isolated in this project. If the BEPE grant application is also accepted, anti-MRSA bacteriophages will be explored in the search for new bioactive agents against these multi-resistant bacteria.