AUTHOR=Wang Guizhen , Gao Yawen , Wang Hongsu , Niu Xiaodi , Wang Jianfeng 

TITLE=Baicalin Weakens Staphylococcus aureus Pathogenicity by Targeting Sortase B

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 8 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00418

DOI=10.3389/fcimb.2018.00418

ISSN=2235-2988

ABSTRACT=Staphylococcus aureus (S. aureus) is a human and animal co-pathogenic bacterium that contributes to the primary aetiology of nosocomial pneumonia, a disease with high mortality rates and costs. Treatment for multiple resistant S. aureus infection is extremely challenging. New alternative therapeutic strategies beyond antibiotic treatment are essential. Anti-virulence agents that specifically target the molecular determinants of virulence may be an alternative method to treat resistant nosocomial infections. SortaseB（SrtB）is a crucial virulence factor found in S. aureus that plays an important role during infection. In this essay, we find that baicalin has a suppressive effect on the activity of SrtB. Minimum inhibitory concentration and growth curve assays confirmed that baicalin has no anti-S. aureus properties. We performed live/dead, LDH, adherence and enzyme-linked immune-sorbent assays to confirm that baicalin reduces injury to human alveolus epithelial A549 cells caused by S. aureus, reduces the adherence of S. aureus to A549 cells, and significantly attenuates the inflammation response of mouse macrophage cells (J774) caused by S. aureus. Additionally, we were able to elucidate the binding mechanics and identify the 
active site of baicalin and SrtB based on molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching. Finally, we confirmed that baicalin directly binds to the active centre of SrtB and residues Asn92 and Tyr128 play an important role in the interaction of SrtB and baicalin. Taken together, these data indicate that baicalin is a possible candidate to combat S.aureus infections.