Influence of iron and aeration on Staphylococcus aureus growth, metabolism, and transcription.
Staphylococcus aureus is a prominent nosocomial pathogen and a major cause of biomaterial-associated infections. The success of S. aureus as a pathogen is due in part to its ability to adapt to stressful environments. As an example, the transition from residing in the nares to residing in the blood or deeper tissues is accompanied by changes in the availability of nutrients and elements such as oxygen and iron. As such, nutrients, oxygen, and iron are important determinants of virulence factor synthesis in S. aureus. In addition to influencing virulence factor synthesis, oxygen and iron are critical cofactors in enzymatic and electron transfer reactions; thus, a change in iron or oxygen availability alters the bacterial metabolome. Changes in metabolism create intracellular signals that alter the activity of metabolite-responsive regulators such as CodY, RpiRc, and CcpA. To assess the extent of metabolomic changes associated with oxygen and iron limitation, S. aureus cells were cultivated in iron-limited medium and/or with decreasing aeration, and the metabolomes were examined by nuclear magnetic resonance (NMR) spectroscopy. As expected, oxygen and iron limitation dramatically decreased tricarboxylic acid (TCA) cycle activity, creating a metabolic block and significantly altering the metabolome. These changes were most prominent during post-exponential-phase growth, when TCA cycle activity was maximal. Importantly, many of the effects of iron limitation were obscured by aeration limitation. Aeration limitation not only obscured the metabolic effects of iron limitation but also overrode the transcription of iron-regulated genes. Finally, in contrast to previous speculation, we confirmed that acidification of the culture medium occurs independent of the availability of iron.
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Nagender
N
Ledala
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Bo
B
Zhang
Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Javier
J
Seravalli
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Robert
R
Powers
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA gsomerville3@unl.edu.
Greg A
GA
Somerville
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002952:Citric Acid Cycle; D004734:Energy Metabolism / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007501:Iron / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D001426:Bacterial Proteins; D007501:Iron; D010100:Oxygen