Triclosan, a widely used antibacterial agent, possesses potent activity against Staphylococcus aureus. This study reports on an investigation of the antibacterial target of triclosan in this pathogen. A strain of S. aureus overexpressing the enoyl-[acyl-carrier-protein] reductase (FabI), demonstrated by Western immunoblotting, gave rise to an increase in the MIC of triclosan, while susceptibilities to a range of unrelated antibacterials were unaffected. There are approximately 12 000 molecules of FabI per cell in mid-log phase growth. This number increased by approximately three- to four-fold in the S. aureus FabI overexpressor. Triclosan selectively inhibited the incorporation of [(14)C]acetate into TCA-precipitable product, an indicator of fatty acid biosynthesis. Furthermore, it inhibited de novo fatty acid biosynthesis in this organism. In vitro, triclosan inhibited recombinant, purified S. aureus FabI with an IC(50) of approximately 1 microM. The combination of these biochemical and genetic data provide further evidence that the mode of action of triclosan in S. aureus is via inhibition of FabI.
In August 2018, Public Health England (PHE) was made aware of five probable cases of Shiga toxin‐producing Escherichia coli (STEC) O157:H7 among individuals reporting participation in a mud‐based obstacle race. An additional four cases, identified via routine whole‐genome sequencing, were subsequently linked to the same event. Two of the nine cases were due to secondary household transmission. Despite an agreement between the event organizers and the local authority, to ensure that all livestock were removed from the site 28 days before the event, sheep were observed grazing on some of the routes taken by the runners 2 days prior to the race taking place. A retrospective review of incidents reported to PHE between 2015 and 2018 identified 41 cases of gastroenteritis associated with muddy assault course events. Of these, 25 cases were due to infection with STEC O157:H7, of which all but one were associated with outbreaks. Due to the environment in which such events take place, it is impossible to entirely remove the risk of exposure to potentially pathogenic zoonoses. However, race organizers should ensure that livestock are removed from the course 28 days before the event. They should also ensure that participants are made aware of the risk of contracting gastrointestinal disease from the environment, and to stress the importance of hand hygiene post‐event and the risk of secondary transmission, particularly to children who are at risk of developing haemolytic uraemic syndrome.
In an assessment of antibiotic action on Staphylococcus aureus, we found that distinct changes in intracellular nucleotide pools occur depending on the antibiotic mode of action. In particular, we have quantitated the effect of antibiotics on pools of the nucleotide guanosine 3'-diphosphate, 5'-triphosphate (pppGpp). Intracellular pppGpp levels increased in response to treatment with the isoleucyl tRNA synthetase inhibitor mupirocin, the uncoupler carbonyl cyanide-m-chlorophenylhydrazone, and rifampicin. These compounds were distinguishable by the degree in which they increased the pppGpp pool and by their differential effect on the pools of other nucleotides. This technique has been used to confirm and to refute the expected mode of action of several compounds identified as possible inhibitors of tRNA synthetases. Our results provide the framework for using nucleotide analysis in the assessment of novel antimicrobial compounds with unknown modes of action.
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