Transcriptome Analysis and Weighted Gene Co-expression Network Reveal Multitarget-Directed Antibacterial Mechanisms of Benzyl Isothiocyanate against Staphylococcus aureus

Staphylococcus aureus can cause
many diseases and has a strong tendency to develop resistance to multiple
antibiotics. In this study, benzyl isothiocyanate (BITC) was shown
to have an excellent inhibitory effect on S. aureus ATCC25923 and methicillin-resistant S. aureus strains, with a minimum inhibitory concentration of 10 μg/mL.
Under a scanning electron microscope, shrinkage and lysis of the cellular
envelope were observed when exposed to BITC, and a bactericidal mode
of BITC against S. aureus was further
confirmed through flow cytometry. Additionally, the RNA profiles of S. aureus cells exposed to BITC indicated a violent
transcriptional response to BITC. Through Kyoto Encyclopedia of Genes
and Genomes analysis, it was found that many pathways involving bacterial
survival were significantly affected, such as RNA degradation, oxidative
phosphorylation, arginine biosynthesis, and so forth. A gene co-expression
network was constructed using weighted gene co-expression network
analysis, and six biologically meaningful co-expression modules and
125 hub genes were identified from the network. Among them, EfeB,
GroES, SmpB, and Lsp were possibly targeted by BITC, leading to the
death of S. aureus. Our results indicated
a great potential of BITC to be applied in food safety and pharmaceuticals,
highlighting its multitarget-directed bactericidal effects on S. aureus.