Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content>
ABSTRACT Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans. To better understand the importance of man...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-02-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00764-19 |
| _version_ | 1818826665972727808 |
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| author | Jessica K. Kajfasz Callahan Katrak Tridib Ganguly Jonathan Vargas Logan Wright Zachary T. Peters Grace A. Spatafora Jacqueline Abranches José A. Lemos |
| author_facet | Jessica K. Kajfasz Callahan Katrak Tridib Ganguly Jonathan Vargas Logan Wright Zachary T. Peters Grace A. Spatafora Jacqueline Abranches José A. Lemos |
| author_sort | Jessica K. Kajfasz |
| collection | DOAJ |
| description | ABSTRACT Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans. To better understand the importance of manganese homeostasis to S. mutans pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of S. mutans UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire sloABC operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here mntH, that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of sloC, which encodes the lipoprotein receptor of the SloABC system, or of mntH alone had no major consequence for the overall fitness of S. mutans, simultaneous inactivation of sloC and mntH (ΔsloC ΔmntH) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contained intracellular levels of Mn similar to those seen with the parent strain, whereas Mn was nearly undetectable in the ΔsloC ΔmntH strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions and that maintenance of Mn homeostasis is essential for the expression of major virulence attributes in S. mutans. IMPORTANCE As transition biometals such as manganese (Mn) are essential for all forms of life, the ability to scavenge biometals in the metal-restricted host environment is an important trait of successful cariogenic pathobionts. Here, we showed that the caries pathogen Streptococcus mutans utilizes two Mn transport systems, namely, SloABC and MntH, to acquire Mn from the environment and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate S. mutans with dental caries. Our results indicate that the development of strategies to deprive S. mutans of Mn hold promise in the combat against this important bacterial pathogen. |
| first_indexed | 2024-12-19T00:31:17Z |
| format | Article |
| id | doaj.art-4a39beab002143eab65b05a5c7e26630 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T00:31:17Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-4a39beab002143eab65b05a5c7e266302022-12-21T20:45:05ZengAmerican Society for MicrobiologymSphere2379-50422020-02-015110.1128/mSphere.00764-19Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content>Jessica K. Kajfasz0Callahan Katrak1Tridib Ganguly2Jonathan Vargas3Logan Wright4Zachary T. Peters5Grace A. Spatafora6Jacqueline Abranches7José A. Lemos8Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USADepartment of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USADepartment of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USADepartment of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USADepartment of Biology, Middlebury College, Middlebury, Vermont, USADepartment of Biology, Middlebury College, Middlebury, Vermont, USADepartment of Biology, Middlebury College, Middlebury, Vermont, USADepartment of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USADepartment of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida, USAABSTRACT Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans. To better understand the importance of manganese homeostasis to S. mutans pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of S. mutans UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire sloABC operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here mntH, that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of sloC, which encodes the lipoprotein receptor of the SloABC system, or of mntH alone had no major consequence for the overall fitness of S. mutans, simultaneous inactivation of sloC and mntH (ΔsloC ΔmntH) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contained intracellular levels of Mn similar to those seen with the parent strain, whereas Mn was nearly undetectable in the ΔsloC ΔmntH strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions and that maintenance of Mn homeostasis is essential for the expression of major virulence attributes in S. mutans. IMPORTANCE As transition biometals such as manganese (Mn) are essential for all forms of life, the ability to scavenge biometals in the metal-restricted host environment is an important trait of successful cariogenic pathobionts. Here, we showed that the caries pathogen Streptococcus mutans utilizes two Mn transport systems, namely, SloABC and MntH, to acquire Mn from the environment and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate S. mutans with dental caries. Our results indicate that the development of strategies to deprive S. mutans of Mn hold promise in the combat against this important bacterial pathogen.https://journals.asm.org/doi/10.1128/mSphere.00764-19S. mutansmanganesemetal transportstress responsedental cariesbiofilm |
| spellingShingle | Jessica K. Kajfasz Callahan Katrak Tridib Ganguly Jonathan Vargas Logan Wright Zachary T. Peters Grace A. Spatafora Jacqueline Abranches José A. Lemos Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> mSphere S. mutans manganese metal transport stress response dental caries biofilm |
| title | Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> |
| title_full | Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> |
| title_fullStr | Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> |
| title_full_unstemmed | Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> |
| title_short | Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of <named-content content-type="genus-species">Streptococcus mutans</named-content> |
| title_sort | manganese uptake mediated by sloabc and mnth is essential for the fitness of named content content type genus species streptococcus mutans named content |
| topic | S. mutans manganese metal transport stress response dental caries biofilm |
| url | https://journals.asm.org/doi/10.1128/mSphere.00764-19 |
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