Interestingly, CidA was up-regulated Carfilzomib during ML and LL phases which could generate similar phenotype as down-regulating lrg. However, mutations in both lrg and CidA caused aberrant biofilm maturation, suggesting that imbalance in their gene expression could CHIR-99021 disrupt biofilm development. These effects of CCG-203592 may increase biofilm formation, which could be outweighed by the effects of down-regulation of other genes by CCG-203592. As a result, the combined effect of all the affected genes by CCG-203592 may produce net decrease of biofilm formation. Interestingly, CCG-203592 decreased the RNAIII level slightly, suggesting that up-regulation of RNAIII level by decreased SigB and CodY level was compensated by changes in other genes that may also regulate RNAIII level. CodY is another global gene regulator that represses agr and icaADBC operon. Inhibition of CodY could have different effects on biofilm formation. Inactivating CodY could enhance biofilm formation in S. aurues strain SA564 and UAMS-1, but reduce biofilm formation in high-biofilmproducing S. arueus isolate S30. More genes were affected by CCG-203592 at stationary phase than at growing phases. We also observed that an analog of CCG203592 changed expression of more genes at stationary phase than at growing phases in GAS. It was well known that expression patterns of many genes are changed at different growth phases. For example, depletion of glucose and change of pH after a long period of culture at stationary phase could impact the gene expression of agr system. As a result, it is possible that CCG203592 has different impacts on gene expression at different growth phases. In order to understand the mechanism of action of this novel anti-virulence compound, further studies on the impact of gene expression changes at different growth phases on biofilm formation are needed. Of note, some of the genes that have been down-regulated also play important roles in staphylococcus virulence. SPA, Hla and PSMs are virulence factors and 
sspB plays important roles in staphylococcus evasion and resistance to host defense. Based on the gene profile changes by CCG-203592, downregulation of these genes could lead to defects in biofilm formation at different stages and could also lead to diminished virulence. In conclusion, this class of novel anti-virulence compounds demonstrates inhibitory effects on gene expression of multiple S. aureus virulence factors, especially genes known to be involved in biofilm formation, resulting in significant inhibition of biofilm formation. The compounds also inhibit SK gene expression in GAS, suggesting that this class of compounds could target a gene regulatory mechanism that is conserved between GAS and S. aureus. This class of compounds could be a starting point for development of novel anti-microbial agents against multiple pathogens. Oversulfated chondroitin sulfate, a member of the family of glycosaminoglycans which includes, heparin, heparan sulfate, dextran sulfate, chondroitin sulfate A, CSB, CS-C, CS-E and their oversulfated forms, was found to be a major contaminant in heparin during the period of time in 2007�C 2008 with increased heparin adverse events. Clinical symptoms induced by OSCS-contaminated heparin included: hypotension, nausea and shortness of breath within 5 to 10 minutes after intravenous injection of the drug.