Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum

ABSTRACT Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise...

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Autores principales:	Sagi Huja, Yaara Oren, Dvora Biran, Susann Meyer, Ulrich Dobrindt, Joerg Bernhard, Doerte Becher, Michael Hecker, Rotem Sorek, Eliora Z. Ron
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6fc1e84e3de148b599990342744d47e3
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spelling	oai:doaj.org-article:6fc1e84e3de148b599990342744d47e32021-11-15T15:47:22ZFur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum10.1128/mBio.01460-142150-7511https://doaj.org/article/6fc1e84e3de148b599990342744d47e32014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01460-14https://doaj.org/toc/2150-7511ABSTRACT Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise highly toxic to most bacteria. To understand how these bacteria survive and grow in serum, we performed system-wide analyses of their response to serum, making a clear distinction between the responses to nutritional immunity and innate immunity. Thus, mild heat inactivation of serum destroys the immune complement and abolishes the bactericidal effect of serum (inactive serum), making it possible to examine nutritional immunity. We used a combination of deep RNA sequencing and proteomics in order to characterize ExPEC genes whose expression is affected by the nutritional stress of serum and by the immune complement. The major change in gene expression induced by serum—active and inactive—involved metabolic genes. In particular, the serum metabolic response is coordinated by three transcriptional regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of the serum-induced transcriptional response. Consistent with its role as a major serum response regulator, deletion of Fur renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in colisepticemia and virulence. IMPORTANCE Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains have emerged as major pathogens, especially in community- and hospital-acquired infections. These bacteria cause a large spectrum of syndromes, the most serious of which is septicemia, a condition with a high mortality rate. These bacterial strains are characterized by high resistance to serum, otherwise highly toxic to most bacteria. To understand the basis of this resistance, we carried out system-wide analyses of the response of ExPEC strains to serum by using proteomics and deep RNA sequencing. The major changes in gene expression induced by exposure to serum involved metabolic genes, not necessarily implicated in relation to virulence. One metabolic regulator—Fur—involved in iron metabolism was responsible for more than 80% of the serum-induced response, and its deletion renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in virulence.Sagi HujaYaara OrenDvora BiranSusann MeyerUlrich DobrindtJoerg BernhardDoerte BecherMichael HeckerRotem SorekEliora Z. RonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Sagi Huja Yaara Oren Dvora Biran Susann Meyer Ulrich Dobrindt Joerg Bernhard Doerte Becher Michael Hecker Rotem Sorek Eliora Z. Ron Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
description	ABSTRACT Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise highly toxic to most bacteria. To understand how these bacteria survive and grow in serum, we performed system-wide analyses of their response to serum, making a clear distinction between the responses to nutritional immunity and innate immunity. Thus, mild heat inactivation of serum destroys the immune complement and abolishes the bactericidal effect of serum (inactive serum), making it possible to examine nutritional immunity. We used a combination of deep RNA sequencing and proteomics in order to characterize ExPEC genes whose expression is affected by the nutritional stress of serum and by the immune complement. The major change in gene expression induced by serum—active and inactive—involved metabolic genes. In particular, the serum metabolic response is coordinated by three transcriptional regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of the serum-induced transcriptional response. Consistent with its role as a major serum response regulator, deletion of Fur renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in colisepticemia and virulence. IMPORTANCE Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains have emerged as major pathogens, especially in community- and hospital-acquired infections. These bacteria cause a large spectrum of syndromes, the most serious of which is septicemia, a condition with a high mortality rate. These bacterial strains are characterized by high resistance to serum, otherwise highly toxic to most bacteria. To understand the basis of this resistance, we carried out system-wide analyses of the response of ExPEC strains to serum by using proteomics and deep RNA sequencing. The major changes in gene expression induced by exposure to serum involved metabolic genes, not necessarily implicated in relation to virulence. One metabolic regulator—Fur—involved in iron metabolism was responsible for more than 80% of the serum-induced response, and its deletion renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in virulence.
format	article
author	Sagi Huja Yaara Oren Dvora Biran Susann Meyer Ulrich Dobrindt Joerg Bernhard Doerte Becher Michael Hecker Rotem Sorek Eliora Z. Ron
author_facet	Sagi Huja Yaara Oren Dvora Biran Susann Meyer Ulrich Dobrindt Joerg Bernhard Doerte Becher Michael Hecker Rotem Sorek Eliora Z. Ron
author_sort	Sagi Huja
title	Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
title_short	Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
title_full	Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
title_fullStr	Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
title_full_unstemmed	Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum
title_sort	fur is the master regulator of the extraintestinal pathogenic <named-content content-type="genus-species">escherichia coli</named-content> response to serum
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/6fc1e84e3de148b599990342744d47e3
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Fur Is the Master Regulator of the Extraintestinal Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Response to Serum

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