Effect Of Staphyloxanthin On Photodynamic Antimicrobial Therapy

Staphylococcus aureus(S.aureus),a typical gram-positive opportunistic pathogen that can cause a variety of human disease,has a notorious capacity to acquire multidrug resistance.With the rapid increase in the number and range of antibiotic-resistant S.aureus strains,traditional antibiotic therapy is gradually ineffective against it.Therefore,we urgently need to explore new and alternative antimicrobial therapies.Among others,photodynamic antimicrobial chemotherapy(PACT)has been widely concerned and studied due to its unique antibacterial mechanism through reactive oxygen species(ROS),which can kill the drug-resistant microorganism efficiently without developing any potential resistance to the photodynamic treatment.Staphyloxanthin(STX)is a virulence factor of S.aureus which is located on the cell membrane.It is a a non-enzymatic antioxidant which plays an important role in the fitness of S.aureus in bad environment and cope with oxidativet stress.The effect of PACT largely depends on the ROS level produced by photosensitizer under illumination,and STX is a natural antioxidant,so this paper aims to explore the effect of STX on PACT.First,we extracted and purified STX from S.aureus ATCC 6538,and then added the purified STX into the bacterial suspension for PACT.It was found that bactericidal effect of PACT was attenuated by the purified STX in a dose-dependent manner.Then we found that purified STX could reduce the ROS level produced by the photosensitizer Zn Pc-(Lys)5 under red light irradiation in a dose-dependent manner.This indicated that the attenuated bactercidal effect of PACT brought by STX may be related to the antioxidant activity of STX which can scavenge ROS.In addition,we also found that STX can form a complex with Zn Pc-(Lys)5 to further weaken the antimicrobial effect of PACT.Next,we confirmed that 10 ?M naftifine hydrochloride can inhibit the STX sythesis without affecting the growth of S.aureus.Based on this,we explored the effect of naftifine hydrochloride on PACT killing S.aureus with two phthalocyanine photosensitizers in vitro.We found that compared with untreated S.aureus,the susceptibility of PACT against S.aureus treated with naftifene hydrochloride was significantly enhanced,i.e.,naftifene hydrochloride increased the antimicrobial effect of PACT against S.aureus.Further studies suggested that the phenomenon may be contributed to that naftifene hydrochloride blocked S.aureus STX sythesis,thereby increasing the membrane permeability of S.aureus,and promoting intracellular ROS generation during PACT process.Taken together,we believe that STX is a limiting factor of PACT which can improve the bacterial survival rate among this process.Therefore,the combination of PACT and inhibitor of STX biosynthesis can achieve a synergistic bactericidal effect on S.aureus.This paper provides a new idea and strategy for the development of rapid and effective anti-S.aureus therapies.