ニュース

Journal:  mBio

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

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.

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.

Keywords: Providencia; T3SS; plasmid.

Hassanさん（2019年3月修了、現バングラデシュ農業大学 獣医学部 教授）が大学院生の頃に行っていた研究をまとめた成果がmBio誌に掲載されました。

プロビデンシア属細菌は、知名度こそ高くはありませんが、本属に含まれるP. alcalifaciensは日本で集団食中毒を引き起こしたこともあります。ただし、プロビデンシア属細菌が病原菌なのか、非病原菌なのか、あるいは特定の性状を持ったものだけが病原性をもつのかについては明確にされていませんでした。
我々の研究グループでは、下痢患児から原因菌として分離したP. rustigianiiの性状を詳細に解析する中で、以下のことを世界で初めて明らかにしました。

①本菌株が接合伝達プラスミド性の3型分泌装置を保有すること。

②本菌の腸管病原性には、この3型分泌装置が必須であること。

③この3型分泌装置をコードする遺伝子群は、下痢の原因菌として分離されたP. alcalifaciensにも保存されていること。

本研究成果が、今後プロビデンシア属菌の病原メカニズムを明らかにしていくための足掛かりになるものと期待されます。