Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates

ABSTRACT Vibrio cholerae genome sequences were analyzed for variation in the rtxA gene that encodes the multifunctional autoprocessing RTX (MARTX) toxin. To accommodate genomic analysis, a discrepancy in the annotated rtxA start site was resolved experimentally. The correct start site is an ATG down...

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Autores principales:	Jazel Dolores, Karla J. F. Satchell
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0d80fc546bd0403c8e17704ae9f2d18c
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spelling	oai:doaj.org-article:0d80fc546bd0403c8e17704ae9f2d18c2021-11-15T15:40:27ZAnalysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates10.1128/mBio.00624-122150-7511https://doaj.org/article/0d80fc546bd0403c8e17704ae9f2d18c2013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00624-12https://doaj.org/toc/2150-7511ABSTRACT Vibrio cholerae genome sequences were analyzed for variation in the rtxA gene that encodes the multifunctional autoprocessing RTX (MARTX) toxin. To accommodate genomic analysis, a discrepancy in the annotated rtxA start site was resolved experimentally. The correct start site is an ATG downstream from rtxC resulting in a gene of 13,638 bp and deduced protein of 4,545 amino acids. Among the El Tor O1 and closely related O139 and O37 genomes, rtxA was highly conserved, with nine alleles differing by only 1 to 6 nucleotides in 100 years. In contrast, 12 alleles from environment-associated isolates are highly variable, at 1 to 3% by nucleotide and 3 to 7% by amino acid. The difference in variation rates did not represent a bias for conservation of the El Tor rtxA compared to that of other strains but rather reflected the lack of gene variation in overall genomes. Three alleles were identified that would affect the function of the MARTX toxin. Two environmental isolates carry novel arrangements of effector domains. These include a variant from RC385 that would suggest an adenylate cyclase toxin and from HE-09 that may have actin ADP-ribosylating activity. Within the recently emerged altered El Tor strains that have a classical ctxB gene, a mutation arose in rtxA that introduces a premature stop codon that disabled toxin function. This null mutant is the genetic background for subsequent emergence of the ctxB7 allele resulting in the strain that spread into Haiti in 2010. Thus, similar to classical strains, the altered El Tor pandemic strains eliminated rtxA after acquiring a classical ctxB. IMPORTANCE Pathogen evolution involves both gain and loss of factors that influence disease. In the environment, bacteria evolve rapidly, with nucleotide diversity arising by genetic modification. Such is occurring with Vibrio cholerae, exemplified by extensive diversity and unique variants of the rtxA-encoded multifunctional autoprocessing RTX (MARTX) toxin among environment-associated strains that cause localized diarrheal outbreaks and food-borne disease. In contrast, seventh pandemic El Tor V. cholerae strains associated with severe diarrhea have changed minimally until the altered El Tor emerged as the most frequent cause of cholera, including in the 2010 Haiti epidemic. These strains have increased virulence attributed to a new variant of the major virulence factor, cholera toxin. It is revealed that these strains also have an inactivated MARTX toxin gene. A similar inactivation occurred during classical cholera pandemics, highlighting that evolution of El Tor cholera is following a similar path of increased dependence on cholera toxin, while eliminating other secreted factors.Jazel DoloresKarla J. F. SatchellAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jazel Dolores Karla J. F. Satchell Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
description	ABSTRACT Vibrio cholerae genome sequences were analyzed for variation in the rtxA gene that encodes the multifunctional autoprocessing RTX (MARTX) toxin. To accommodate genomic analysis, a discrepancy in the annotated rtxA start site was resolved experimentally. The correct start site is an ATG downstream from rtxC resulting in a gene of 13,638 bp and deduced protein of 4,545 amino acids. Among the El Tor O1 and closely related O139 and O37 genomes, rtxA was highly conserved, with nine alleles differing by only 1 to 6 nucleotides in 100 years. In contrast, 12 alleles from environment-associated isolates are highly variable, at 1 to 3% by nucleotide and 3 to 7% by amino acid. The difference in variation rates did not represent a bias for conservation of the El Tor rtxA compared to that of other strains but rather reflected the lack of gene variation in overall genomes. Three alleles were identified that would affect the function of the MARTX toxin. Two environmental isolates carry novel arrangements of effector domains. These include a variant from RC385 that would suggest an adenylate cyclase toxin and from HE-09 that may have actin ADP-ribosylating activity. Within the recently emerged altered El Tor strains that have a classical ctxB gene, a mutation arose in rtxA that introduces a premature stop codon that disabled toxin function. This null mutant is the genetic background for subsequent emergence of the ctxB7 allele resulting in the strain that spread into Haiti in 2010. Thus, similar to classical strains, the altered El Tor pandemic strains eliminated rtxA after acquiring a classical ctxB. IMPORTANCE Pathogen evolution involves both gain and loss of factors that influence disease. In the environment, bacteria evolve rapidly, with nucleotide diversity arising by genetic modification. Such is occurring with Vibrio cholerae, exemplified by extensive diversity and unique variants of the rtxA-encoded multifunctional autoprocessing RTX (MARTX) toxin among environment-associated strains that cause localized diarrheal outbreaks and food-borne disease. In contrast, seventh pandemic El Tor V. cholerae strains associated with severe diarrhea have changed minimally until the altered El Tor emerged as the most frequent cause of cholera, including in the 2010 Haiti epidemic. These strains have increased virulence attributed to a new variant of the major virulence factor, cholera toxin. It is revealed that these strains also have an inactivated MARTX toxin gene. A similar inactivation occurred during classical cholera pandemics, highlighting that evolution of El Tor cholera is following a similar path of increased dependence on cholera toxin, while eliminating other secreted factors.
format	article
author	Jazel Dolores Karla J. F. Satchell
author_facet	Jazel Dolores Karla J. F. Satchell
author_sort	Jazel Dolores
title	Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
title_short	Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
title_full	Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
title_fullStr	Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
title_full_unstemmed	Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates
title_sort	analysis of <named-content content-type="genus-species">vibrio cholerae</named-content> genome sequences reveals unique <italic toggle="yes">rtxa</italic> variants in environmental strains and an <italic toggle="yes">rtxa</italic>-null mutation in recent altered el tor isolates
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0d80fc546bd0403c8e17704ae9f2d18c
work_keys_str_mv	AT jazeldolores analysisofnamedcontentcontenttypegenusspeciesvibriocholeraenamedcontentgenomesequencesrevealsuniqueitalictoggleyesrtxaitalicvariantsinenvironmentalstrainsandanitalictoggleyesrtxaitalicnullmutationinrecentalteredeltorisolates AT karlajfsatchell analysisofnamedcontentcontenttypegenusspeciesvibriocholeraenamedcontentgenomesequencesrevealsuniqueitalictoggleyesrtxaitalicvariantsinenvironmentalstrainsandanitalictoggleyesrtxaitalicnullmutationinrecentalteredeltorisolates
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Analysis of <named-content content-type="genus-species">Vibrio cholerae</named-content> Genome Sequences Reveals Unique <italic toggle="yes">rtxA</italic> Variants in Environmental Strains and an <italic toggle="yes">rtxA</italic>-Null Mutation in Recent Altered El Tor Isolates

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