Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy

ABSTRACT Most urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC), which depends on an extracellular organelle (type 1 pili) for adherence to bladder cells during infection. Type 1 pilus expression is partially regulated by inversion of a piece of DNA referred to as f...

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Autores principales:	Colin W. Russell, Rashmi Sukumaran, Lu Ting Liow, Balamurugan Periaswamy, Shazmina Rafee, Yuemin C. Chee, Swaine L. Chen
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	type 1 pili genomics information theory phase variation structural variations uropathogenic Escherichia coli Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2b73f03afa7a410eb2865abc01d9134e
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spelling	oai:doaj.org-article:2b73f03afa7a410eb2865abc01d9134e2021-11-15T15:22:22ZComprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy10.1128/mSphere.00693-182379-5042https://doaj.org/article/2b73f03afa7a410eb2865abc01d9134e2019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00693-18https://doaj.org/toc/2379-5042ABSTRACT Most urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC), which depends on an extracellular organelle (type 1 pili) for adherence to bladder cells during infection. Type 1 pilus expression is partially regulated by inversion of a piece of DNA referred to as fimS, which contains the promoter for the fim operon encoding type 1 pili. fimS inversion is regulated by up to five recombinases collectively known as Fim recombinases. These Fim recombinases are currently known to regulate two other switches: the ipuS and hyxS switches. A long-standing question has been whether the Fim recombinases regulate the inversion of other switches, perhaps to coordinate expression for adhesion or virulence. We answered this question using whole-genome sequencing with a newly developed algorithm (structural variation detection using relative entropy [SVRE]) for calling structural variations using paired-end short-read sequencing. SVRE identified all of the previously known switches, refining the specificity of which recombinases act at which switches. Strikingly, we found no new inversions that were mediated by the Fim recombinases. We conclude that the Fim recombinases are each highly specific for a small number of switches. We hypothesize that the unlinked Fim recombinases have been recruited to regulate fimS, and fimS only, as a secondary locus; this further implies that regulation of type 1 pilus expression (and its role in gastrointestinal and/or genitourinary colonization) is important enough, on its own, to influence the evolution and maintenance of multiple additional genes within the accessory genome of E. coli. IMPORTANCE UTI is a common ailment that affects more than half of all women during their lifetime. The leading cause of UTIs is UPEC, which relies on type 1 pili to colonize and persist within the bladder during infection. The regulation of type 1 pili is remarkable for an epigenetic mechanism in which a section of DNA containing a promoter is inverted. The inversion mechanism relies on what are thought to be dedicated recombinase genes; however, the full repertoire for these recombinases is not known. We show here that there are no additional targets beyond those already identified for the recombinases in the entire genome of two UPEC strains, arguing that type 1 pilus expression itself is the driving evolutionary force for the presence of these recombinase genes. This further suggests that targeting the type 1 pilus is a rational alternative nonantibiotic strategy for the treatment of UTI.Colin W. RussellRashmi SukumaranLu Ting LiowBalamurugan PeriaswamyShazmina RafeeYuemin C. CheeSwaine L. ChenAmerican Society for Microbiologyarticletype 1 piligenomicsinformation theoryphase variationstructural variationsuropathogenic Escherichia coliMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 1 pili genomics information theory phase variation structural variations uropathogenic Escherichia coli Microbiology QR1-502
spellingShingle	type 1 pili genomics information theory phase variation structural variations uropathogenic Escherichia coli Microbiology QR1-502 Colin W. Russell Rashmi Sukumaran Lu Ting Liow Balamurugan Periaswamy Shazmina Rafee Yuemin C. Chee Swaine L. Chen Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
description	ABSTRACT Most urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC), which depends on an extracellular organelle (type 1 pili) for adherence to bladder cells during infection. Type 1 pilus expression is partially regulated by inversion of a piece of DNA referred to as fimS, which contains the promoter for the fim operon encoding type 1 pili. fimS inversion is regulated by up to five recombinases collectively known as Fim recombinases. These Fim recombinases are currently known to regulate two other switches: the ipuS and hyxS switches. A long-standing question has been whether the Fim recombinases regulate the inversion of other switches, perhaps to coordinate expression for adhesion or virulence. We answered this question using whole-genome sequencing with a newly developed algorithm (structural variation detection using relative entropy [SVRE]) for calling structural variations using paired-end short-read sequencing. SVRE identified all of the previously known switches, refining the specificity of which recombinases act at which switches. Strikingly, we found no new inversions that were mediated by the Fim recombinases. We conclude that the Fim recombinases are each highly specific for a small number of switches. We hypothesize that the unlinked Fim recombinases have been recruited to regulate fimS, and fimS only, as a secondary locus; this further implies that regulation of type 1 pilus expression (and its role in gastrointestinal and/or genitourinary colonization) is important enough, on its own, to influence the evolution and maintenance of multiple additional genes within the accessory genome of E. coli. IMPORTANCE UTI is a common ailment that affects more than half of all women during their lifetime. The leading cause of UTIs is UPEC, which relies on type 1 pili to colonize and persist within the bladder during infection. The regulation of type 1 pili is remarkable for an epigenetic mechanism in which a section of DNA containing a promoter is inverted. The inversion mechanism relies on what are thought to be dedicated recombinase genes; however, the full repertoire for these recombinases is not known. We show here that there are no additional targets beyond those already identified for the recombinases in the entire genome of two UPEC strains, arguing that type 1 pilus expression itself is the driving evolutionary force for the presence of these recombinase genes. This further suggests that targeting the type 1 pilus is a rational alternative nonantibiotic strategy for the treatment of UTI.
format	article
author	Colin W. Russell Rashmi Sukumaran Lu Ting Liow Balamurugan Periaswamy Shazmina Rafee Yuemin C. Chee Swaine L. Chen
author_facet	Colin W. Russell Rashmi Sukumaran Lu Ting Liow Balamurugan Periaswamy Shazmina Rafee Yuemin C. Chee Swaine L. Chen
author_sort	Colin W. Russell
title	Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
title_short	Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
title_full	Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
title_fullStr	Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
title_full_unstemmed	Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy
title_sort	comprehensive identification of fim-mediated inversions in uropathogenic <named-content content-type="genus-species">escherichia coli</named-content> with structural variation detection using relative entropy
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2b73f03afa7a410eb2865abc01d9134e
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Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic <named-content content-type="genus-species">Escherichia coli</named-content> with Structural Variation Detection Using Relative Entropy

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