Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.

Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, the SCHU strain of F. tularensis SCHU P0 maintained by passaging in artificial media has been found to be attenuated. To better understand the molecular mechanisms b...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Akihiko Uda, Tsuyoshi Sekizuka, Kiyoshi Tanabayashi, Osamu Fujita, Makoto Kuroda, Akitoyo Hotta, Naoko Sugiura, Neekun Sharma, Shigeru Morikawa, Akio Yamada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f5d9151ba0d447db6e69230e176184c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0f5d9151ba0d447db6e69230e176184c
record_format	dspace
spelling	oai:doaj.org-article:0f5d9151ba0d447db6e69230e176184c2021-11-18T08:32:11ZRole of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.1932-620310.1371/journal.pone.0089075https://doaj.org/article/0f5d9151ba0d447db6e69230e176184c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24558472/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, the SCHU strain of F. tularensis SCHU P0 maintained by passaging in artificial media has been found to be attenuated. To better understand the molecular mechanisms behind the pathogenicity of F. tularensis SCHU, we attempted to isolate virulent bacteria by serial passages in mice. SCHU P5 obtained after 5th passages in mice remained avirulent, while SCHU P9 obtained after 9th passages was completely virulent in mice. Moreover, SCHU P9 grew more efficiently in J774.1 murine macrophages compared with that in the less pathogenic SCHU P0 and P5. Comparison of the nucleotide sequences of the whole genomes of SCHU P0, P5, and P9 revealed only 1 nucleotide difference among P0, P5 and P9 in 1 of the 2 copies of pathogenicity determinant protein C (pdpC) gene. An adenine residue deletion was observed in the pdpC1 gene of SCHU P0, P5, and P9 and in the pdpC2 gene of SCHU P0, and P5, while P9 was characterized by the wild type pdpC2 gene. Thus, SCHU P0 and P5 expressed only truncated forms of PdpC protein, while SCHU P9 expressed both wild type and truncated versions. To validate the pathogenicity of PdpC, both copies of the pdpC gene in SCHU P9 have been inactivated by Targetron mutagenesis. SCHU P9 mutants with inactivated pdpC gene showed low intracellular growth in J774.1 cells and did not induce severe disease in experimentally infected mice, while virulence of the mutants was restored by complementation with expression of the intact PdpC. These results demonstrate that PdpC is crucial in determining the virulence of F. tularensis SCHU.Akihiko UdaTsuyoshi SekizukaKiyoshi TanabayashiOsamu FujitaMakoto KurodaAkitoyo HottaNaoko SugiuraNeekun SharmaShigeru MorikawaAkio YamadaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89075 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akihiko Uda Tsuyoshi Sekizuka Kiyoshi Tanabayashi Osamu Fujita Makoto Kuroda Akitoyo Hotta Naoko Sugiura Neekun Sharma Shigeru Morikawa Akio Yamada Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
description	Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, the SCHU strain of F. tularensis SCHU P0 maintained by passaging in artificial media has been found to be attenuated. To better understand the molecular mechanisms behind the pathogenicity of F. tularensis SCHU, we attempted to isolate virulent bacteria by serial passages in mice. SCHU P5 obtained after 5th passages in mice remained avirulent, while SCHU P9 obtained after 9th passages was completely virulent in mice. Moreover, SCHU P9 grew more efficiently in J774.1 murine macrophages compared with that in the less pathogenic SCHU P0 and P5. Comparison of the nucleotide sequences of the whole genomes of SCHU P0, P5, and P9 revealed only 1 nucleotide difference among P0, P5 and P9 in 1 of the 2 copies of pathogenicity determinant protein C (pdpC) gene. An adenine residue deletion was observed in the pdpC1 gene of SCHU P0, P5, and P9 and in the pdpC2 gene of SCHU P0, and P5, while P9 was characterized by the wild type pdpC2 gene. Thus, SCHU P0 and P5 expressed only truncated forms of PdpC protein, while SCHU P9 expressed both wild type and truncated versions. To validate the pathogenicity of PdpC, both copies of the pdpC gene in SCHU P9 have been inactivated by Targetron mutagenesis. SCHU P9 mutants with inactivated pdpC gene showed low intracellular growth in J774.1 cells and did not induce severe disease in experimentally infected mice, while virulence of the mutants was restored by complementation with expression of the intact PdpC. These results demonstrate that PdpC is crucial in determining the virulence of F. tularensis SCHU.
format	article
author	Akihiko Uda Tsuyoshi Sekizuka Kiyoshi Tanabayashi Osamu Fujita Makoto Kuroda Akitoyo Hotta Naoko Sugiura Neekun Sharma Shigeru Morikawa Akio Yamada
author_facet	Akihiko Uda Tsuyoshi Sekizuka Kiyoshi Tanabayashi Osamu Fujita Makoto Kuroda Akitoyo Hotta Naoko Sugiura Neekun Sharma Shigeru Morikawa Akio Yamada
author_sort	Akihiko Uda
title	Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
title_short	Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
title_full	Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
title_fullStr	Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
title_full_unstemmed	Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.
title_sort	role of pathogenicity determinant protein c (pdpc) in determining the virulence of the francisella tularensis subspecies tularensis schu.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0f5d9151ba0d447db6e69230e176184c
work_keys_str_mv	AT akihikouda roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT tsuyoshisekizuka roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT kiyoshitanabayashi roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT osamufujita roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT makotokuroda roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT akitoyohotta roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT naokosugiura roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT neekunsharma roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT shigerumorikawa roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu AT akioyamada roleofpathogenicitydeterminantproteincpdpcindeterminingthevirulenceofthefrancisellatularensissubspeciestularensisschu
_version_	1718421665147256832

Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.

Ejemplares similares