الفهرس 
Screening and evaluation of chemically synthesized anti-virulence compounds as Non-conventional antimicrobial agents against staphylococcus aureus
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Abstract
The emergence of multi-drug resistant bacterial strains has proved the failure of antibiotics as a long-term therapy for S. aureus infection, especially with the limited rate of developing new antibiotics. In this study, the aim was to reduce S. aureus pathogenicity by developing an Agr quorum sensing chemical inhibitor, with minimal impact on viability, thus minimal impact on resistance development. A library of potential anti-Agr chemical compounds was designed and synthesized (31 drugs). These drugs were screened for lack of reduction of bacterial viability and anti-Agr activity; observed by a reduction in virulence. The initial screen employed measuring the optical density of the overnight culture, grown in presence of 40 æM of the drugs. Afterwards, the HA50, which reflects alpha hemolysin (Hla) activity, was measured. In vitro, the expression of virulence factors, in presence of the drugs, has been evaluated phenotypically in sheep blood agar and tributyrin agarose plates. On a transcriptional level, the RNAIII level was measured by real time PCR. The activity of these drugs was validated in vivo, using a murine abscess model. All the drugs had no effect on S. aureus viability. The secondary screen yielded three drugs; 1, 2D, 4B which reduce alpha-hemolytic activity. These drugs were also found to reduce delta-hemolytic activity. Two of them; 1 and 4B were capable of reducing the S. aureus lipolytic activity