A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii

ABSTRACT We have recently described a clinical isolate of Providencia rustigianii strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A cdtB mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The str...

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Main Authors: Jayedul Hassan, Atsushi Hinenoya, Noritoshi Hatanaka, Sharda Prasad Awasthi, Goutham Belagula Manjunath, Nahid Rahman, Jyoji Yamate, Shota Nakamura, Daisuke Motooka, Akira Nagita, Shah M. Faruque, Shinji Yamasaki
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Language:English
Published: American Society for Microbiology 2024-10-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.02297-24
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author Jayedul Hassan
Atsushi Hinenoya
Noritoshi Hatanaka
Sharda Prasad Awasthi
Goutham Belagula Manjunath
Nahid Rahman
Jyoji Yamate
Shota Nakamura
Daisuke Motooka
Akira Nagita
Shah M. Faruque
Shinji Yamasaki
author_facet Jayedul Hassan
Atsushi Hinenoya
Noritoshi Hatanaka
Sharda Prasad Awasthi
Goutham Belagula Manjunath
Nahid Rahman
Jyoji Yamate
Shota Nakamura
Daisuke Motooka
Akira Nagita
Shah M. Faruque
Shinji Yamasaki
author_sort Jayedul Hassan
collection DOAJ
description ABSTRACT We have recently described a clinical isolate of Providencia rustigianii strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A cdtB mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The strain was subjected to phenotypic and genetic analyses including whole genome sequencing (WGS) to explore the genetic determinants of the observed invasiveness and diarrheagenic properties. Analysis and annotation of WGS data revealed the presence of two distinct type III secretion systems (T3SS) in strain JH-1, one of which was located on the chromosome designated as cT3SS (3,992,833 bp) and the other on a mega-plasmid designated as pT3SS (168,819 bp). Comparative genomic analysis revealed that cT3SS is generally conserved in Providencia spp. but pT3SS was limited to a subset of Providencia spp., carrying cdt genes. Strain JH-1 was found to invade HeLa cells and induce fluid accumulation with characteristic pathological lesions in rabbit ileal loops. Remarkably, these phenomena were associated with the pT3SS but not cT3SS. The plasmid could be transferred by conjugation from strain JH-1 to other strains of P. rustigianii, Providencia rettgeri, and Escherichia coli with concomitant transfer of these virulence properties. This is the first report of a functional and mobile T3SS in P. rustigianii and its association with invasiveness and diarrheagenicity of this bacterium. These data suggest that P. rustigianii and other CDT-producing Providencia strains might carry T3SS and exert their diarrheagenic effect by exploiting the T3SS nano-machinery.IMPORTANCEThe precise mechanism of virulence of Providencia rustigianii is unclear, although some strains produce cytolethal distending toxin as a putative virulence factor. We have detected the presence of a type III secretion system (T3SS) for the first time on a plasmid in a P. rustigianii strain. Plasmid-mediated T3SS seems to be directly involved in virulence of P. rustigianii and may serve as a means of horizontal transfer of T3SS genes. Our results may have implication in understanding the mechanism of emergence of new pathogenic strains of P. rustigianii.
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spelling doaj-art-98b0aac38d1e4a8fbb12426e752e68ed2025-08-20T02:16:49ZengAmerican Society for MicrobiologymBio2150-75112024-10-01151010.1128/mbio.02297-24A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianiiJayedul Hassan0Atsushi Hinenoya1Noritoshi Hatanaka2Sharda Prasad Awasthi3Goutham Belagula Manjunath4Nahid Rahman5Jyoji Yamate6Shota Nakamura7Daisuke Motooka8Akira Nagita9Shah M. Faruque10Shinji Yamasaki11Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanGraduate School of Veterinary Science, Osaka Metropolitan University, Osaka, JapanGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanResearch Institute for Microbial Diseases, Osaka University, Osaka, JapanResearch Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Pediatrics, Mizushima Central Hospital, Okayama, JapanSchool of Environment and Life Sciences, Independent University Bangladesh (IUB), Dhaka, BangladeshGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, JapanABSTRACT We have recently described a clinical isolate of Providencia rustigianii strain JH-1 carrying the genes for cytolethal distending toxin (CDT) in a conjugative plasmid. A cdtB mutant of strain JH-1, which lost CDT activity, was still found to retain invasiveness and diarrheagenicity. The strain was subjected to phenotypic and genetic analyses including whole genome sequencing (WGS) to explore the genetic determinants of the observed invasiveness and diarrheagenic properties. Analysis and annotation of WGS data revealed the presence of two distinct type III secretion systems (T3SS) in strain JH-1, one of which was located on the chromosome designated as cT3SS (3,992,833 bp) and the other on a mega-plasmid designated as pT3SS (168,819 bp). Comparative genomic analysis revealed that cT3SS is generally conserved in Providencia spp. but pT3SS was limited to a subset of Providencia spp., carrying cdt genes. Strain JH-1 was found to invade HeLa cells and induce fluid accumulation with characteristic pathological lesions in rabbit ileal loops. Remarkably, these phenomena were associated with the pT3SS but not cT3SS. The plasmid could be transferred by conjugation from strain JH-1 to other strains of P. rustigianii, Providencia rettgeri, and Escherichia coli with concomitant transfer of these virulence properties. This is the first report of a functional and mobile T3SS in P. rustigianii and its association with invasiveness and diarrheagenicity of this bacterium. These data suggest that P. rustigianii and other CDT-producing Providencia strains might carry T3SS and exert their diarrheagenic effect by exploiting the T3SS nano-machinery.IMPORTANCEThe precise mechanism of virulence of Providencia rustigianii is unclear, although some strains produce cytolethal distending toxin as a putative virulence factor. We have detected the presence of a type III secretion system (T3SS) for the first time on a plasmid in a P. rustigianii strain. Plasmid-mediated T3SS seems to be directly involved in virulence of P. rustigianii and may serve as a means of horizontal transfer of T3SS genes. Our results may have implication in understanding the mechanism of emergence of new pathogenic strains of P. rustigianii.https://journals.asm.org/doi/10.1128/mbio.02297-24ProvidenciaT3SSplasmid
spellingShingle Jayedul Hassan
Atsushi Hinenoya
Noritoshi Hatanaka
Sharda Prasad Awasthi
Goutham Belagula Manjunath
Nahid Rahman
Jyoji Yamate
Shota Nakamura
Daisuke Motooka
Akira Nagita
Shah M. Faruque
Shinji Yamasaki
A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
mBio
Providencia
T3SS
plasmid
title A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
title_full A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
title_fullStr A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
title_full_unstemmed A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
title_short A plasmid-mediated type III secretion system associated with invasiveness and diarrheagenicity of Providencia rustigianii
title_sort plasmid mediated type iii secretion system associated with invasiveness and diarrheagenicity of providencia rustigianii
topic Providencia
T3SS
plasmid
url https://journals.asm.org/doi/10.1128/mbio.02297-24
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