Abstract
Two-component systems (TCSs) consist of a histidine kinase and a response regulator. Here, we evaluated the conservation of the AgrAC TCS among 149 completely sequenced Staphylococcus aureus strains. It is composed of four genes: agrBDCA. We found that: (i) AgrAC system (agr) was found in all but one of the 149 strains, (ii) the agr positive strains were further classified into four agr types based on AgrD protein sequences, (iii) the four agr types not only specified the chromosomal arrangement of the agr genes but also the sequence divergence of AgrC histidine kinase protein, which confers signal specificity, (iv) the sequence divergence was reflected in distinct structural properties especially in the transmembrane region and second extracellular binding domain, and (v) there was a strong correlation between the agr type and the virulence genomic profile of the organism. Taken together, these results demonstrate that bioinformatic analysis of the agr locus leads to a classification system that correlates with the presence of virulence factors and protein structural properties.
Highlights
Staphylococcus aureus is a gram positive human pathogen that has evolved considerable antimicrobial resistance during the clinical antibiotic era
We analyzed 149 completely sequenced S. aureus strains from PATRIC database (Wattam et al, 2014) for the presence of agr locus
148 strains were predicted to be positive for agr locus, based on the domain search of histidine kinase and response regulator proteins and querying the neighborhood genes for the presence of agrB and agrD. Out of these 148 Agr positive strains, 85, 42, 16, and 4 strains were predicted as strains belonging to types I, II, III, and IV, respectively. This prediction was made by scanning the AgrD protein sequences by a custom python script for the presence of conserved motif that are present in each autoinducing peptide (AIP) type (Hawver et al, 2016)
Summary
Staphylococcus aureus is a gram positive human pathogen that has evolved considerable antimicrobial resistance during the clinical antibiotic era. It can cause a wide spectrum of infection types and severity, including soft tissue infection, bloodstream infections, pneumonia, osteomyelitis, and nosocomial device related infections (Lowy, 1998; Yarwood and Schlievert, 2003; Tong et al, 2015). AgrAC TCS is encoded by the agr locus and acts as a quorum sensing (QS) system in S. aureus. This QS mechanism modulates gene expression based on population density in response to environmental stimuli
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