Abstract

Biofilm formation is regarded as one of the major determinants in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as pathogens of medical device-related infection. However, methicillin-susceptible S. aureus (MSSA) can also form biofilm in vitro and such biofilms are resistant to vancomycin. Hence, researching the possible mechanisms of MSSA biofilm formation is urgent and necessary. Here, we used S. aureus ATCC25923 as the model strain, and studied gene expression profiles in biofilms after the treatment of ursolic acid and resveratrol using RNA-seq technology. The results showed that only ursolic acid could inhibit biofilm formation, which differed from their applied on the multiple clinical drugs resistant MRSA biofilm. RNA-seq data was validated by examining the expression of six genes involved in biofilm formation by qRT-PCR. These data analysis indicated that the mechanism of the MSSA biofilm formation was different from that of the MRSA, due to absence of accessory gene regulator (agr) function. These findings suggest that biofilms of S. aureus with agr dysfunction may be more resistant than those with agr function. Therefore, the infection from clinical MSSA may be recalcitrant once forming biofilm. Further study is necessary to uncover the mechanisms of biofilm formation in other clinical S. aureus.

Highlights

  • Biofilm formation is regarded as one of the major determinants in the prevalence of methicillinresistant Staphylococcus aureus (MRSA) as pathogens of medical device-related infection

  • The susceptibility of the methicillin-susceptible S. aureus (MSSA) planktonic cells to ursolic acid was determined in vitro by methods recommended by the Clinical and Laboratory Standards Institute (CLSI)

  • The results showed that the Minimal inhibitory concentration (MIC) of ursolic acid against S. aureus ATCC25923 was 60 μ g/mL

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Summary

Introduction

Biofilm formation is regarded as one of the major determinants in the prevalence of methicillinresistant Staphylococcus aureus (MRSA) as pathogens of medical device-related infection. RNA-seq data was validated by examining the expression of six genes involved in biofilm formation by qRT-PCR These data analysis indicated that the mechanism of the MSSA biofilm formation was different from that of the MRSA, due to absence of accessory gene regulator (agr) function. We confirmed that S. aureus ATCC25923, an agr-III strain which is a quality control strain in antimicrobial susceptibility test, is capable to form biofilm in vitro These findings led to the hypothesis that S. aureus may developed its ability to form a thick biofilm due to agr-locus inactivation, which does not correlate to the antibiotic resistance. To investigate the potential mechanisms of MSSA biofilm formation at the genetic level, we used high-throughout Illumina sequencing of cDNA (Illumina RNA-seq) to study the differentially expressed genes of S. aureus ATCC25923 in biofilm that was treated with ursolic acid and resveratrol, respectively. These results were compared with the genes expression of MRSA in biofilms under the same conditions[18]

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Conclusion

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