| Title: | An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle Arrest in Yeast |
| Author(s): | Arellano VJ; Martinell Garcia P; Rodriguez Plaza JG; Lara Ortiz MT; Schreiber G; Volkmer R; Klipp E; Rio GD; |
| Address: | "Departamento de Bioquimica y Biologia Estructural, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. Theoretische Biophysik, Humboldt-Universitat zu Berlin, Berlin, Germany. Institut fur Medizinische Immunologie, Charite - Universitatsmedizin Berlin, Berlin, Germany. Leibniz-Institut fur Molekulare Pharmakologie, Berlin, Germany" |
| ISSN/ISBN: | 1664-302X (Print) 1664-302X (Electronic) 1664-302X (Linking) |
| Abstract: | "Although most antibiotics act on cells that are actively dividing and non-dividing cells such as in microbe sporulation or cancer stem cells represent a new paradigm for the control of disease. In addition to their relevance to health, such antibiotics may promote our understanding of the relationship between the cell cycle and cell death. No antibiotic specifically acting on microbial cells arrested in their cell cycle has been identified until the present time. In this study we used an antimicrobial peptide derived from alpha-pheromone, IP-1, targeted against MATa Saccharomyces cerevisiae cells in order to assess its dependence on cell cycle arrest to kill cells. Analysis by flow cytometry and fluorescence microscopy of various null mutations of genes involved in biological processes activated by the pheromone pathway (the mitogen-activated protein kinase pathway, cell cycle arrest, cell proliferation, autophagy, calcium influx) showed that IP-1 requires arrest in G(0)/G(1) in order to kill yeast cells. Isolating cells in different cell cycle phases by elutriation provided further evidence that entry into cell cycle arrest, and not into G(1) phase, is necessary if our peptide is to kill yeast cells. We also describe a variant of IP-1 that does not activate the pheromone pathway and consequently does not kill yeast cells that express the pheromone's receptor; the use of this variant peptide in combination with different cell cycle inhibitors that induce cell cycle arrest independently of the pheromone pathway confirmed that it is cell cycle arrest that is required for the cell death induced by this peptide in yeast. We show that the cell death induced by IP-1 differs from that induced by alpha-pheromone and depends on FIG1 in a way independent of the cell cycle arrest induced by the pheromone. Thus, IP-1 is the first molecule described that specifically kills microbial cells during cell cycle arrest, a subject of interest beyond the process of mating in yeast cells. The experimental system described in this study should be useful in the study of the mechanisms at play in the communication between cell cycle arrest and cell death on other organisms, hence promoting the development of new antibiotics" |
| Keywords: | Saccharomyces cerevisiae antimicrobial peptide cell cycle arrest cell death cytometry gene deletions microscopy pheromone pathway; |
| Notes: | "PubMed-not-MEDLINEArellano, Vladimir J Martinell Garcia, Paula Rodriguez Plaza, Jonathan G Lara Ortiz, Maria T Schreiber, Gabriele Volkmer, Rudolf Klipp, Edda Rio, Gabriel Del eng Switzerland 2018/07/03 Front Microbiol. 2018 Jun 14; 9:1240. doi: 10.3389/fmicb.2018.01240. eCollection 2018" |
