Lysogeny with Shiga Toxin 2-Encoding Bacteriophages Represses Type III Secretion in Enterohemorrhagic Escherichia coli

PLoS Pathogens

Mark E. J. Woolhouse¹  Margo E. Chase-Topping¹  Stefano Morabito²  Rosangela Tozzoli²  David L. Gally³  Eliza B. K. Wolfson³  Jai J. Tree³  Arvind Mahajan³  Xuefang Xu³  Sean P. McAteer³  Andrew J. Roe⁴  Scott A. Beatson⁵  Lesley J. Allison⁶  Darren J. Shaw⁷ 

[1] Centre for Immunity, Infection & Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom;European Union Reference Laboratory for Escherichia coli, Istituto Superiore di Sanitá, Dipartimento di Sanitá Pubblica Veterinaria e Sicurezza Alimentare, Rome, Italy;Immunity and Infection Division, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom;Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Glasgow Biomedical Research Centre, Glasgow, United Kingdom;School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia;Scottish E. coli VTEC Reference Laboratory, Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom;Veterinary Clinical Sciences, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom

关键词: Bacteriophages;    Regulator genes;    Lysogeny;    Toxins;    Comparative genomics;    Secretion;    Viral genomics;    Enterohaemorrhagic Escherichia coli;   

DOI  :  10.1371/journal.ppat.1002672

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins.

【 授权许可】

CC BY