title: Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.
abstract: Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Abraham
authors.initials: A
authors.lastname: Lin
authors.forename: Jose
authors.initials: J
authors.lastname: Jimenez
authors.forename: Julien
authors.initials: J
authors.lastname: Derr
authors.forename: Pedro
authors.initials: P
authors.lastname: Vera
authors.forename: Michael L
authors.initials: ML
authors.lastname: Manapat
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Esvelt
authors.forename: Laura
authors.initials: L
authors.lastname: Villanueva
authors.forename: David R
authors.initials: DR
authors.lastname: Liu
authors.forename: Irene A
authors.initials: IA
authors.lastname: Chen
mesh_terms: D017104:Bacteriophage M13 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003227:Conjugation, Genetic; D004926:Escherichia coli / Q000254:growth & development / Q000821:virology; D005144:F Factor / Q000378:metabolism; D005814:Genes, Viral / Q000235:genetics; D008954:Models, Biological; D018933:Pili, Sex / Q000378:metabolism; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins