Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design
The worldwide spread of antimicrobial resistance highlights the need of new druggable cellular targets. The increasing knowledge of bacterial cell division suggested the potentiality of this pathway as a pool of alternative drug targets, mainly based on the essentiality of these proteins, as well as...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/12/841 |
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| author | Gabriele Trespidi Viola Camilla Scoffone Giulia Barbieri Giovanna Riccardi Edda De Rossi Silvia Buroni |
| author_facet | Gabriele Trespidi Viola Camilla Scoffone Giulia Barbieri Giovanna Riccardi Edda De Rossi Silvia Buroni |
| author_sort | Gabriele Trespidi |
| collection | DOAJ |
| description | The worldwide spread of antimicrobial resistance highlights the need of new druggable cellular targets. The increasing knowledge of bacterial cell division suggested the potentiality of this pathway as a pool of alternative drug targets, mainly based on the essentiality of these proteins, as well as on the divergence from their eukaryotic counterparts. People suffering from cystic fibrosis are particularly challenged by the lack of antibiotic alternatives. Among the opportunistic pathogens that colonize the lungs of these patients, <i>Burkholderia cenocepacia</i> is a well-known multi-drug resistant bacterium, particularly difficult to treat. Here we describe the organization of its division cell wall (<i>dcw</i>) cluster: we found that 15 genes of the <i>dcw</i> operon can be transcribed as a polycistronic mRNA from <i>mraZ</i> to <i>ftsZ</i> and that its transcription is under the control of a strong promoter regulated by MraZ. <i>B. cenocepacia</i> J2315 FtsZ was also shown to interact with the other components of the divisome machinery, with a few differences respect to other bacteria, such as the direct interaction with FtsQ. Using an in vitro sedimentation assay, we validated the role of SulA as FtsZ inhibitor, and the roles of FtsA and ZipA as tethers of FtsZ polymers. Together our results pave the way for future antimicrobial design based on the divisome as pool of antibiotic cellular targets. |
| first_indexed | 2024-03-10T14:35:35Z |
| format | Article |
| id | doaj.art-11e30e0b960448e8a33971bc52a67b41 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T14:35:35Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-11e30e0b960448e8a33971bc52a67b412023-11-20T22:11:54ZengMDPI AGAntibiotics2079-63822020-11-0191284110.3390/antibiotics9120841Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial DesignGabriele Trespidi0Viola Camilla Scoffone1Giulia Barbieri2Giovanna Riccardi3Edda De Rossi4Silvia Buroni5Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, ItalyThe worldwide spread of antimicrobial resistance highlights the need of new druggable cellular targets. The increasing knowledge of bacterial cell division suggested the potentiality of this pathway as a pool of alternative drug targets, mainly based on the essentiality of these proteins, as well as on the divergence from their eukaryotic counterparts. People suffering from cystic fibrosis are particularly challenged by the lack of antibiotic alternatives. Among the opportunistic pathogens that colonize the lungs of these patients, <i>Burkholderia cenocepacia</i> is a well-known multi-drug resistant bacterium, particularly difficult to treat. Here we describe the organization of its division cell wall (<i>dcw</i>) cluster: we found that 15 genes of the <i>dcw</i> operon can be transcribed as a polycistronic mRNA from <i>mraZ</i> to <i>ftsZ</i> and that its transcription is under the control of a strong promoter regulated by MraZ. <i>B. cenocepacia</i> J2315 FtsZ was also shown to interact with the other components of the divisome machinery, with a few differences respect to other bacteria, such as the direct interaction with FtsQ. Using an in vitro sedimentation assay, we validated the role of SulA as FtsZ inhibitor, and the roles of FtsA and ZipA as tethers of FtsZ polymers. Together our results pave the way for future antimicrobial design based on the divisome as pool of antibiotic cellular targets.https://www.mdpi.com/2079-6382/9/12/841cell divisionFtsZ<i>Burkholderia cenocepacia</i>drug resistancenew drug targets |
| spellingShingle | Gabriele Trespidi Viola Camilla Scoffone Giulia Barbieri Giovanna Riccardi Edda De Rossi Silvia Buroni Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design Antibiotics cell division FtsZ <i>Burkholderia cenocepacia</i> drug resistance new drug targets |
| title | Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design |
| title_full | Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design |
| title_fullStr | Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design |
| title_full_unstemmed | Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design |
| title_short | Molecular Characterization of the <i>Burkholderia cenocepacia</i> <i>dcw</i> Operon and FtsZ Interactors as New Targets for Novel Antimicrobial Design |
| title_sort | molecular characterization of the i burkholderia cenocepacia i i dcw i operon and ftsz interactors as new targets for novel antimicrobial design |
| topic | cell division FtsZ <i>Burkholderia cenocepacia</i> drug resistance new drug targets |
| url | https://www.mdpi.com/2079-6382/9/12/841 |
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