Elucidate Regulatory Networks That Drive Staphylococcal Lipoprotein Expression

Abstract

Staphylococcus aureus (S. aureus) is a leading pathogen of bacterial infection in health care and community based settings. The community- acquired methicillin-resistant S. aureus (MRSA) has rapidly become the most widely reported resistant pathogen identified in several parts of the world that is associated with high morbidity and mortality. As metal ions are essential cofactors in almost all basic metabolic pathways in S. aureus, the promoters of the targeted genes were cloned and then evaluated in terms of their activity and their effect on S. aureus growth in presence or absence of the different metals (iron, zinc, manganese, and cupper). The reporter plasmid pHC48 with a red fluorescence protein and the promoter of the S. aureus sarA gene was used to construct several reporter plasmids carrying promoters from characterized (copL, mntC and uncharacterized Lpps (SAUSA300_1478, SAUSA300_2315) and they were investigated in term of the promoter activity and their effect on the bacterial growth in presence and absence of different metals. Results: We didn’t obtain results with the reporter plasmid (pHC48_PmntC), while the other used reporter plasmids displayed a wide range of differential degree of promoter activity on the selected gene expression and growth of S. aureus under the different metals. Conclusion: The current study high lightened the central role of SarA in biosynthesis of virulence determinants in S. aureus. We characterized novel genes of unknown function in S. aureus, proposed to have a role in S. aureus virulence through regulation of staphylococcal Lpps. The current study provides new insights about a novel Lpps in S. aureus that could play a role in survival under metal stress. The current results may hold opportunities to emerge novel anti-bacterial strategies to address the ongoing challenge of MRSA. Further studies are needed to fully characterize the unknown Lpps with their targeted genes.