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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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| 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. |
| format | Article |
| id | doaj-art-c6ca3b79e71841d5a28e9867fa23750f |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| 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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