title: Simulation of the M13 life cycle II: Investigation of the control mechanisms of M13 infection and establishment of the carrier state.
abstract: Bacteriophage M13 is a true parasite of bacteria, able to co-opt the infected cell and control the production of progeny across many cellular generations. Here, our genetically-structured simulation of M13 is applied to quantitatively dissect the interplay between the host cellular environment and the controlling interactions governing the phage life cycle during the initial establishment of infection and across multiple cell generations. Multiple simulations suggest that phage-encoded feedback interactions constrain the utilization of host DNA polymerase, RNA polymerase and ribosomes. The simulation reveals the importance of p5 translational attenuation in controlling the production of phage double-stranded DNA and suggests an underappreciated role for p5 translational self-attenuation in resource allocation. The control elements active in a single generation are sufficient to reproduce the experimentally-observed multigenerational curing of the phage infection. Understanding the subtleties of regulation will be important for maximally exploiting M13 particles as scaffolds for nanoscale devices.
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors: Steven W
authors: SW
authors: Smeal
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors: Margaret A
authors: MA
authors: Schmitt
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors: Ronnie Rodrigues
authors: RR
authors: Pereira
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors: Ashok
authors: A
authors: Prasad
authors: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA; Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: nickfisk@colostate.edu.
authors: John D
authors: JD
authors: Fisk
mesh_terms: D017104:Bacteriophage M13 / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000821:virology*; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins
keywords: Computational biology; Genetically-structured simulation; M13 bacteriophage; Systems biology; Virus life cycle