Cadmium stress dictates central carbon flux and alters membrane composition in Streptococcus pneumoniae

• Type of Material: Article
• Authors: Stephanie L. Neville, University of Melbourne; Bart A. Eijkelkamp, Flinders University South Australia; Amber Lothian, University of Melbourne; James C. Paton, University of Adelaide; Blaine Roberts, Emory University; Jason W. Rosch, St Jude Children's Research Hospital; Christopher A. McDevitt, University of Melbourne
• Language: English
• Date: 2020-12-19
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s42003-020-01417-y
• Title of Journal or Parent Work: COMMUNICATIONS BIOLOGY
• Volume: 3
• Issue: 1
• Start Page: 694
• End Page: 694
• Grant/Funding Information: This work was supported by the National Health and Medical Research Council (NHMRC) Program Grant 1071659 to J.C.P., Project Grants 1080784 and 1122582 to C.A.M., and the Australian Research Council (ARC) Discovery Project Grant DP170102102 to J.C.P. and C.A.M. S.L.N. is an NHMRC Early Career Research Fellow (1142695) and C.A.M. is an ARC Future Fellow (FT170100006). J.W.R is supported by 1U01AI124302, 1RO1AI110618, and by ALSAC. B.R.R acknowledges receiving partial support from the NHMRC (1061550 & 1138673), and the Motor Neuron Disease Research Institute of Australia
• Keywords: ACETYL-COA CARBOXYLASE; Science & Technology - Other Topics; COMPETENCE; Life Sciences & Biomedicine; GROWTH-RATE REGULATION; PNEUMOCOCCAL PATHOGENESIS; GENOME SEQUENCE; HEAVY-METALS; Biology; FATTY-ACID BIOSYNTHESIS; OXIDATIVE STRESS; Science & Technology; Multidisciplinary Sciences; GENETIC-TRANSFORMATION; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; Life Sciences & Biomedicine - Other Topics
• Research Categories: Biology, Cell; Biology, Genetics

Abstract

Metal ion homeostasis is essential for all forms of life. However, the breadth of intracellular impacts that arise upon dysregulation of metal ion homeostasis remain to be elucidated. Here, we used cadmium, a non-physiological metal ion, to investigate how the bacterial pathogen, Streptococcus pneumoniae, resists metal ion stress and dyshomeostasis. By combining transcriptomics, metabolomics and metalloproteomics, we reveal that cadmium stress dysregulates numerous essential cellular pathways including central carbon metabolism, lipid membrane biogenesis and homeostasis, and capsule production at the transcriptional and/or functional level. Despite the breadth of cellular pathways susceptible to metal intoxication, we show that S. pneumoniae is able to maintain viability by utilizing cellular pathways that are predominately metal-independent, such as the pentose phosphate pathway to maintain energy production. Collectively, this work provides insight into the cellular processes impacted by cadmium and how resistance to metal ion toxicity is achieved in S. pneumoniae.