Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences

Pilla, G., McVicker, G. ORCID: 0000-0002-6967-5968 and Tang, C.M., 2017. Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences. PLOS Genetics, 13 (9), e1007014. ISSN 1553-7404

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Abstract

Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segrega tional killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecula r recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS 1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.

Item Type: Journal article
Publication Title: PLOS Genetics
Creators: Pilla, G., McVicker, G. and Tang, C.M.
Publisher: Public Library of Science
Date: 2017
Volume: 13
Number: 9
ISSN: 1553-7404
Identifiers:
NumberType
10.1371/journal.pgen.1007014DOI
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 17 Oct 2017 10:58
Last Modified: 17 Oct 2017 10:58
URI: http://irep.ntu.ac.uk/id/eprint/31822

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