Journal article
Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis
Proceedings of the National Academy of Sciences - PNAS, Vol.107(37), pp.16286-16290
09/14/2010
DOI: 10.1073/pnas.1008368107
PMCID: PMC2941286
PMID: 20805502
Abstract
During bacterial cannibalism, a differentiated subpopulation harvests nutrients from their genetically identical siblings to allow continued growth in nutrient-limited conditions. Hypothesis-driven imaging mass spectrometry (IMS) was used to identify metabolites active in a Bacillus subtilis cannibalism system in which sporulating cells lyse nonsporulating siblings. Two candidate molecules with sequences matching the products of skfA and sdpC, genes for the proposed cannibalistic factors sporulation killing factor (SKF) and sporulation delaying protein (SDP), respectively, were identified and the structures of the final products elucidated. SKF is a cyclic 26-amino acid (aa) peptide that is posttranslationally modified with one disulfide and one cysteine thioether bridged to the α-position of a methionine, a posttranslational modification not previously described in biology. SDP is a 42-residue peptide with one disulfide bridge. In spot test assays on solid medium, overproduced SKF and SDP enact a cannibalistic killing effect with SDP having higher potency. However, only purified SDP affected B. subtilis cells in liquid media in fluorescence microscopy and growth assays. Specifically, SDP treatment delayed growth in a concentration-dependent manner, caused increases in cell permeability, and ultimately caused cell lysis accompanied by the production of membrane tubules and spheres. Similarly, SDP but not SKF was able to inhibit the growth of the pathogens Staphylococcus aureus and Staphylococcus epidermidis with comparable IC50 to vancomycin. This investigation, with the identification of SKF and SDP structures, highlights the strength of IMS in investigations of metabolic exchange of microbial colonies and also demonstrates IMS as a promising approach to discover novel biologically active molecules.
Details
- Title: Subtitle
- Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis
- Creators
- Wei-Ting Liu - Department of Chemistry and BiochemistryYu-Liang Yang - Skaggs School of Pharmacy and Pharmaceutical SciencesYuquan Xu - Skaggs School of Pharmacy and Pharmaceutical SciencesAnne Lamsa - Division of Biological SciencesNina M Haste - Skaggs School of Pharmacy and Pharmaceutical SciencesJane Y Yang - Department of Chemistry and BiochemistryJulio Ng - Department of Computer ScienceDavid Gonzalez - Department of Chemistry and BiochemistryCraig D Ellermeier - Department of MicrobiologyPaul D Straight - Department of Biochemistry and BiophysicsPavel A Pevzner - Department of Computer ScienceJoe Pogliano - Division of Biological SciencesVictor Nizet - Skaggs School of Pharmacy and Pharmaceutical SciencesKit Pogliano - Division of Biological SciencesPieter C Dorrestein - Department of Chemistry and Biochemistry
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.107(37), pp.16286-16290
- DOI
- 10.1073/pnas.1008368107
- PMID
- 20805502
- PMCID
- PMC2941286
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 09/14/2010
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083889002771
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