Proteomic and Metabolomic Analyses of a Tea-Tree Oil-Selected Staphylococcus aureus Small Colony Variant

Abstract

Tea tree oil (TTO) is hypothesized to kill bacteria by indiscriminately denaturing membrane and protein structures. A Staphylococcus aureus small colony variant (SCV) selected with TTO (SH1000-TTORS-1) demonstrated slowed growth, reduced susceptibility to TTO, a diminutive cell size, and a thinned cell wall. Utilizing a proteomics and metabolomics approach, we have now revealed that the TTO-selected SCV mutant demonstrated defective fatty acid synthesis, an alteration in the expression of genes and metabolites associated with central metabolism, the induction of a general stress response, and a reduction of proteins critical for active growth and translation. SH1000-TTORS-1 also demonstrated an increase in amino acid accumulation and a decrease in sugar content. The reduction in glycolytic pathway proteins and sugar levels indicated that carbon flow through glycolysis and gluconeogenesis is reduced in SH1000-TTORS-1. The increase in amino acid accumulation coincides with the reduced production of translation-specific proteins and the induction of proteins associated with the stringent response. The decrease in sugar content likely deactivates catabolite repression and the increased amino acid pool observed in SH1000-TTORS-1 represents a potential energy and carbon source which could maintain carbon flow though the tricarboxylic acid (TCA) cycle. It is noteworthy that processes that contribute to the production of the TTO targets (proteins and membrane) are reduced in SH1000-TTORS-1. This is one of a few studies describing a mechanism that bacteria utilize to withstand the action of an antiseptic which is thought to inactivate multiple cellular targets.

Comparative Proteomic and Morphological Change Analyses of Staphylococcus aureus During Resuscitation From Prolonged Freezing

“…FabD is an NADH-dependent component that increases the synthesis of cell membrane fatty acids ( Hong et al, 2010 ). FabD also showed a greater abundance in tea tree oil-selected S. aureus SCVs ( Torres et al, 2017 ). FapR is a transcriptional factor participating in bacteria membrane synthesis.…”

Transcriptome and Proteome of Methicillin-Resistant Staphylococcus aureus Small-Colony Variants Reveal Changed Metabolism and Increased Immune Evasion

“…As SCV strains have become a major clinical problem, an increasing number of studies are being conducted to elucidate their formation and functional mechanisms. Based on transcriptome or proteome technology, many studies have already identified the altered metabolome of an SCV strain selected with tea tree oil ( 16 ), compared the genome and transcriptome of an initial S. aureus WT isolate and stable SCV relapse isolates from a prosthetic joint infection ( 17 ), and conducted proteomic analyses with SCV phenotypes (e.g., clinically derived SCVs, hemB mutant, and gentamicin-induced SCVs) and normal strains (e.g., clinical wild-type strain, complemented hemB mutant, and spontaneous revertant of clinical SCVs) ( 18 ). In our study, taking advantage of advanced technologies such as RNA sequencing and protein mass spectrometry, we obtained the transcriptomic and proteomic profiles of normal strain IE1 and SCV strain IE2.…”