Integration of metabolomics and transcriptomics indicates changes in MRSA exposed to terpinen-4-ol

Abstract

Background This study investigated the effects of terpinen-4-ol on methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, and the possible mechanisms governing this effect. Results We observed that terpinen-4-ol has good antibacterial activity and inhibits the formation of MRSA biofilm. The MIC and MBC values for terpinen-4-ol against S. aureus were 0.08% ~ 0.32%. And terpinen-4-ol at 0.32% could kill all bacteria and clear all biofilms. Untargeted metabolomic and transcriptomic analyses showed that terpinen-4-ol strongly inhibited DNA and RNA biosynthesis in MRSA at 2 h after treatment by affecting genes and metabolites related to purine and pyrimidine metabolic pathways. Some differential genes which play important roles in DNA synthesis and the production of eDNA from biofilm exposed to terpinen-4-ol was also significantly decreased compared with that of the control. Conclusions Terpinen-4-ol has good antibacterial activity and significantly inhibits the formation of MRSA biofilm by inhibiting purine and pyrimidine metabolism.

First Evidence of a Combination of Terpinen-4-ol and α-Terpineol as a Promising Tool against ESKAPE Pathogens

“…Time kill assays confirm the bactericidal properties of Synterpicine™ on Staphylococcus aureus, Escherichia coli , MRSA and Pseudomonas aeruginosa in less than 1 h at 4×MICs, which is faster than ampicillin on Staphylococcus aureus , amoxicillin on Escherichia coli and gentamicin on Pseudomonas aeruginosa in standard conditions. These results are in accordance with previously published results with terpinen-4-ol [ 16 , 56 ] and α-terpineol [ 35 ] alone. Time kill assays thus support standard MBC assays, and show that Synterpicine™ is an efficient bactericide against Staphylococcus aureus , MRSA, Escherichia coli and Pseudomonas aeruginosa , making this mixture of terpinen-4-ol and α-terpineol a good antibacterial natural candidate.…”

“…Hence, the respective MBCs and MICs of Synterpicine™ are identical ( Klebsiella pneumoniae , Pseudomonas aeruginosa ) or differ from a maximum of one serial dilution ( Staphylococcus aureus , MRSA, Enterococcus faecium , Staphylococcus aureus , Acinetobacter baumannii , and Enterobacter cloacae ). Similar results have been observed previously for terpinene-4-ol alone, with a MIC/MBC ratio of 1:2 on Staphylococcus strains [ 18 , 56 ].…”

Comprehensive Study of Components and Antimicrobial Properties of Essential Oil Extracted from Carum carvi L. Seeds

“…Previous studies have reported similar findings. Terpinen-4-ol, the primary constituent of tea tree oil, has been found to destroy MRSA biofilm by inhibiting the biosynthesis of pyrimidine nucleotides [ 41 ].…”