Marion Duprilot1, Dominique Decre1,2, Nathalie Genel1, Laurence Drieux1,3, Wladimir Sougakoff1,3, Guillaume Arlet1,2. 1. Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. 2. Laboratoire de Bactériologie, AP-HP, Groupe Hospitalier des Hôpitaux Universitaires de l'Est Parisien, AP-HP, Paris, France. 3. Laboratoire de Bactériologie, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP, Paris, France.
Abstract
Objectives: To explore the VagCD toxin-antitoxin (TA) systems encoded on plasmids in multiresistant Klebsiella pneumoniae strains. Methods: Previously sequenced K. pneumoniae plasmids were used for in silico analysis and a collection of 63 resistant K. pneumoniae strains was used for epidemiological study. Functional analysis was done after separate cloning of the toxin gene under the control of the arabinose-inducible promoter of pBAD43 and of the antitoxin gene under the control of the constitutive promoter of pUC19. Results: In silico , two types of VagCD systems, VagCD1 and VagCD2, encoded on K. pneumoniae plasmids could be distinguished, 15% carrying one of these TA systems. Moreover, in a collection of antibiotic-resistant K. pneumoniae strains including ESBL or carbapenemase producers, 17.5% of isolates were found to harbour a VagCD TA system. VagCD1 and VagCD2 were proved functional TA systems, with VagD the toxin and VagC its antitoxin, not only in K. pneumoniae but also in Escherichia coli and other Enterobacteriaceae. Toxin expression was found to induce a significant decrease in a bacterial population resulting from both bactericidal and bacteriostatic effects. Conclusions: The vagCD genes of K. pneumoniae encode a functional broad-spectrum TA system and are conserved on the large multiple antibiotic resistance-conferring plasmids in this species.
Objectives: To explore the VagCD toxin-antitoxin (TA) systems encoded on plasmids in multiresistant Klebsiella pneumoniae strains. Methods: Previously sequenced K. pneumoniae plasmids were used for in silico analysis and a collection of 63 resistant K. pneumoniae strains was used for epidemiological study. Functional analysis was done after separate cloning of the toxin gene under the control of the arabinose-inducible promoter of pBAD43 and of the antitoxin gene under the control of the constitutive promoter of pUC19. Results: In silico , two types of VagCD systems, VagCD1 and VagCD2, encoded on K. pneumoniae plasmids could be distinguished, 15% carrying one of these TA systems. Moreover, in a collection of antibiotic-resistant K. pneumoniae strains including ESBL or carbapenemase producers, 17.5% of isolates were found to harbour a VagCD TA system. VagCD1 and VagCD2 were proved functional TA systems, with VagD the toxin and VagC its antitoxin, not only in K. pneumoniae but also in Escherichia coli and other Enterobacteriaceae. Toxin expression was found to induce a significant decrease in a bacterial population resulting from both bactericidal and bacteriostatic effects. Conclusions: The vagCD genes of K. pneumoniae encode a functional broad-spectrum TA system and are conserved on the large multiple antibiotic resistance-conferring plasmids in this species.
Authors: R Trastoy; T Manso; L Fernández-García; L Blasco; A Ambroa; M L Pérez Del Molino; G Bou; R García-Contreras; T K Wood; M Tomás Journal: Clin Microbiol Rev Date: 2018-08-01 Impact factor: 26.132
Authors: Ines Bleriot; Rocío Trastoy; Lucia Blasco; Felipe Fernández-Cuenca; Antón Ambroa; Laura Fernández-García; Olga Pacios; Elena Perez-Nadales; Julian Torre-Cisneros; Jesús Oteo-Iglesias; Ferran Navarro; Elisenda Miró; Alvaro Pascual; German Bou; Luis Martínez-Martínez; Maria Tomas Journal: Microb Genom Date: 2020-04-29