Research Article

Insights from S. aureus Pangenome along with Agr typing Revealed Agr operon Reduction in Chronic Elderly Patients

Syed Basit Ali Shah, Muhammad Makeen Alam

Abstract :

Staphylococcus aureus (S. aureus) is a pathogen responsible for various infections, including skin and soft tissue infections (SSTI) and bloodstream infections. Methicillin-resistant S. aureus (MRSA) presents treatment challenges due to antibiotic resistance. To investigate the genetic diversity, pangenome structure, and the role of the agr operon in S. aureus using whole-genome analyses. A total of 460 complete S. aureus genomes were retrieved from the NCBI database. Whole-genome average nucleotide identity (ANI) and genome-togenome distance were computed using FASTANI and GGDC, respectively. Metadata, including isolation host, country, and antibiotic resistance, were extracted. Genomes were annotated using Prokka. Pangenome analysis was conducted with Roary, categorizing genes into core, soft core, shell, and cloud. Recombination detection and phylogenetic analysis were performed using Gubbins and FastTree. Agr operon genes were analyzed using in-house scripts for local BLAST searches. The pangenome comprised 6,159 genes, with 2,093 core genes and 3,275 cloud genes. Pangenome analysis revealed an open pangenome. Core genome phylogeny identified significant genetic diversity and distinct population structures. Agr-typing showed dominance of agrI (59.47%) followed by agrII (25.27%) and agrIII (12.85%). One genome lacked the agr operon. The distribution of clonal complexes (CCs) varied, with CC8 being prominent in MRSA genomes. MRSA strains were dominant, especially within CC8, reflecting high methicillin resistance. The study highlights the genetic diversity and adaptability of S. aureus. The agr operon plays a critical role in virulence regulation. The absence of the agr operon in one strain suggests possible niche adaptation. Continuous surveillance and molecular typing are essential to monitor resistant strain’s evolution and spread.

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