The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
ABSTRACT Biofilm-forming bacteria, including the Gram-negative Pseudomonas aeruginosa, cause multiple types of chronic infections and are responsible for serious health burdens in humans, animals, and plants. Nitric oxide (NO) has been shown to induce biofilm dispersal via triggering a reduction in...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00878-20 |
| _version_ | 1818406296180752384 |
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| author | Ji-Su Park Ha-Young Choi Won-Gon Kim |
| author_facet | Ji-Su Park Ha-Young Choi Won-Gon Kim |
| author_sort | Ji-Su Park |
| collection | DOAJ |
| description | ABSTRACT Biofilm-forming bacteria, including the Gram-negative Pseudomonas aeruginosa, cause multiple types of chronic infections and are responsible for serious health burdens in humans, animals, and plants. Nitric oxide (NO) has been shown to induce biofilm dispersal via triggering a reduction in cyclic-di-GMP levels in a variety of bacteria. However, how NO, at homeostatic levels, also facilitates biofilm formation is unknown. Here, we found that complestatin, a structural analog of vancomycin isolated from Streptomyces, inhibits P. aeruginosa biofilm formation by upregulating NO production via nitrite reductase (NIR) induction and c-di-GMP degradation via phosphodiesterase (PDE) stimulation. The complestatin protein target was identified as a nitrite transporter from a genome-wide screen using the Keio Escherichia coli knockout library and confirmed using nitrite transporter knockout and overexpression strains. We demonstrated that the nitrite transporter stimulated biofilm formation by controlled NO production via appropriate NIR suppression and subsequent diguanylate cyclase (DGC) activation, not PDE activity, and c-di-GMP production in E. coli and P. aeruginosa. Thus, this study provides a mechanism for NO-mediated biofilm formation, which was previously not understood. IMPORTANCE Bacterial biofilms play roles in infections and avoidance of host defense mechanisms of medically important pathogens and increase the antibiotic resistance of the bacteria. Nitric oxide (NO) is reported to be involved in both biofilm formation and dispersal, which are conflicting processes. The mechanism by which NO regulates biofilm dispersal is relatively understood, but there are no reports about how NO is involved in biofilm formation. Here, by investigating the mechanism by which complestatin inhibits biofilm formation, we describe a novel mechanism for governing biofilm formation in Escherichia coli and Pseudomonas aeruginosa. Nitrite transporter is required for biofilm formation via regulation of NO levels and subsequent c-di-GMP production. Additionally, the nitrite transporter contributes more to P. aeruginosa virulence than quorum sensing. Thus, this study identifies nitrite transporters as new antibiofilm targets for future practical and therapeutic agent development. |
| first_indexed | 2024-12-14T09:09:41Z |
| format | Article |
| id | doaj.art-8f20a6a7385d4ca2bdbcbbcb412a5781 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T09:09:41Z |
| publishDate | 2020-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-8f20a6a7385d4ca2bdbcbbcb412a57812022-12-21T23:08:35ZengAmerican Society for MicrobiologymBio2150-75112020-08-0111410.1128/mBio.00878-20The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>Ji-Su Park0Ha-Young Choi1Won-Gon Kim2Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of KoreaABSTRACT Biofilm-forming bacteria, including the Gram-negative Pseudomonas aeruginosa, cause multiple types of chronic infections and are responsible for serious health burdens in humans, animals, and plants. Nitric oxide (NO) has been shown to induce biofilm dispersal via triggering a reduction in cyclic-di-GMP levels in a variety of bacteria. However, how NO, at homeostatic levels, also facilitates biofilm formation is unknown. Here, we found that complestatin, a structural analog of vancomycin isolated from Streptomyces, inhibits P. aeruginosa biofilm formation by upregulating NO production via nitrite reductase (NIR) induction and c-di-GMP degradation via phosphodiesterase (PDE) stimulation. The complestatin protein target was identified as a nitrite transporter from a genome-wide screen using the Keio Escherichia coli knockout library and confirmed using nitrite transporter knockout and overexpression strains. We demonstrated that the nitrite transporter stimulated biofilm formation by controlled NO production via appropriate NIR suppression and subsequent diguanylate cyclase (DGC) activation, not PDE activity, and c-di-GMP production in E. coli and P. aeruginosa. Thus, this study provides a mechanism for NO-mediated biofilm formation, which was previously not understood. IMPORTANCE Bacterial biofilms play roles in infections and avoidance of host defense mechanisms of medically important pathogens and increase the antibiotic resistance of the bacteria. Nitric oxide (NO) is reported to be involved in both biofilm formation and dispersal, which are conflicting processes. The mechanism by which NO regulates biofilm dispersal is relatively understood, but there are no reports about how NO is involved in biofilm formation. Here, by investigating the mechanism by which complestatin inhibits biofilm formation, we describe a novel mechanism for governing biofilm formation in Escherichia coli and Pseudomonas aeruginosa. Nitrite transporter is required for biofilm formation via regulation of NO levels and subsequent c-di-GMP production. Additionally, the nitrite transporter contributes more to P. aeruginosa virulence than quorum sensing. Thus, this study identifies nitrite transporters as new antibiofilm targets for future practical and therapeutic agent development.https://journals.asm.org/doi/10.1128/mBio.00878-20biofilmsPseudomonas aeruginosanitric oxidenitrite transporterdrug target |
| spellingShingle | Ji-Su Park Ha-Young Choi Won-Gon Kim The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> mBio biofilms Pseudomonas aeruginosa nitric oxide nitrite transporter drug target |
| title | The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> |
| title_full | The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> |
| title_fullStr | The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> |
| title_full_unstemmed | The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> |
| title_short | The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> |
| title_sort | nitrite transporter facilitates biofilm formation via suppression of nitrite reductase and is a new antibiofilm target in named content content type genus species pseudomonas aeruginosa named content |
| topic | biofilms Pseudomonas aeruginosa nitric oxide nitrite transporter drug target |
| url | https://journals.asm.org/doi/10.1128/mBio.00878-20 |
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