Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways

Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we i...

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Main Authors: Carlos Martínez-Torró, Sergi Torres-Puig, Marta Monge, Lucía Sánchez-Alba, Miguel González-Martín, Marina Marcos-Silva, Alex Perálvarez-Marín, Francesc Canals, Enrique Querol, Jaume Piñol, Oscar Q. Pich
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2019.1700762
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author Carlos Martínez-Torró
Sergi Torres-Puig
Marta Monge
Lucía Sánchez-Alba
Miguel González-Martín
Marina Marcos-Silva
Alex Perálvarez-Marín
Francesc Canals
Enrique Querol
Jaume Piñol
Oscar Q. Pich
author_facet Carlos Martínez-Torró
Sergi Torres-Puig
Marta Monge
Lucía Sánchez-Alba
Miguel González-Martín
Marina Marcos-Silva
Alex Perálvarez-Marín
Francesc Canals
Enrique Querol
Jaume Piñol
Oscar Q. Pich
author_sort Carlos Martínez-Torró
collection DOAJ
description Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the hrl promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the fur mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the fur mutant by ICP-MS revealed an important role of Fur in nickel acquisition.
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spelling doaj-art-c6ca3b79e71841d5a28e9867fa23750f2025-08-20T03:08:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019151910.1080/22221751.2019.1700762Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathwaysCarlos Martínez-Torró0Sergi Torres-Puig1Marta Monge2Lucía Sánchez-Alba3Miguel González-Martín4Marina Marcos-Silva5Alex Perálvarez-Marín6Francesc Canals7Enrique Querol8Jaume Piñol9Oscar Q. Pich10Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainVall d'Hebron Institute of Oncology (VHIO), Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainBiophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, SpainVall d'Hebron Institute of Oncology (VHIO), Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainInstitut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, SpainTransition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the hrl promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the fur mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the fur mutant by ICP-MS revealed an important role of Fur in nickel acquisition.https://www.tandfonline.com/doi/10.1080/22221751.2019.1700762Mycoplasma genitaliumemerging STI pathogennovel therapeutic targetsmetal acquisition systemsFerric uptake regulatorHistidine-rich proteins
spellingShingle Carlos Martínez-Torró
Sergi Torres-Puig
Marta Monge
Lucía Sánchez-Alba
Miguel González-Martín
Marina Marcos-Silva
Alex Perálvarez-Marín
Francesc Canals
Enrique Querol
Jaume Piñol
Oscar Q. Pich
Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
Emerging Microbes and Infections
Mycoplasma genitalium
emerging STI pathogen
novel therapeutic targets
metal acquisition systems
Ferric uptake regulator
Histidine-rich proteins
title Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
title_full Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
title_fullStr Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
title_full_unstemmed Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
title_short Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways
title_sort transcriptional response to metal starvation in the emerging pathogen mycoplasma genitalium is mediated by fur dependent and independent regulatory pathways
topic Mycoplasma genitalium
emerging STI pathogen
novel therapeutic targets
metal acquisition systems
Ferric uptake regulator
Histidine-rich proteins
url https://www.tandfonline.com/doi/10.1080/22221751.2019.1700762
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