<named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy
ABSTRACT Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competito...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02491-18 |
| _version_ | 1818822608619044864 |
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| author | Britney L. Hardy Seth W. Dickey Roger D. Plaut Daniel P. Riggins Scott Stibitz Michael Otto D. Scott Merrell |
| author_facet | Britney L. Hardy Seth W. Dickey Roger D. Plaut Daniel P. Riggins Scott Stibitz Michael Otto D. Scott Merrell |
| author_sort | Britney L. Hardy |
| collection | DOAJ |
| description | ABSTRACT Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest that microbial species-specific interactions can affect human nasal colonization by the opportunistic pathogen Staphylococcus aureus. However, the complex and dynamic molecular interactions that mediate these effects on S. aureus nasal colonization are often difficult to study and remain poorly understood. Here, we show that Corynebacterium pseudodiphtheriticum, a common member of the normal nasal microbiota, mediates contact-independent bactericidal activity against S. aureus, including methicillin-resistant S. aureus (MRSA). Bacterial interaction assays revealed that S. aureus isolates that were spontaneously resistant to C. pseudodiphtheriticum killing could be recovered at a low frequency. To better understand the pathways associated with killing and resistance, a S. aureus transposon mutant library was utilized to select for resistant mutant strains. We found that insertional inactivation of agrC, which codes for the sensor kinase of the Agr quorum sensing (Agr QS) system that regulates expression of many virulence factors in S. aureus, conferred resistance to killing. Analysis of the spontaneously resistant S. aureus isolates revealed that each showed decreased expression of the Agr QS components. Targeted analysis of pathways regulated by Agr QS revealed that loss of the phenol-soluble modulins (PSMs), which are effectors of Agr QS, also conferred resistance to bactericidal activity. Transmission electron microscopy analysis revealed that C. pseudodiphtheriticum induced dramatic changes to S. aureus cell surface morphology that likely resulted in cell lysis. Taken together, these data suggest that C. pseudodiphtheriticum-mediated killing of S. aureus requires S. aureus virulence components. While S. aureus can overcome targeted killing, this occurs at the cost of attenuated virulence; loss of Agr QS activity would phenotypically resemble a S. aureus commensal state that would be unlikely to be associated with disease. Commensal competition resulting in dampened virulence of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds. IMPORTANCE While some individuals are nasally colonized with S. aureus, the underlying factors that determine colonization are not understood. There is increasing evidence that indicates that resident bacteria play a role; some commensal species can eradicate S. aureus from the nasal cavity. Among these, Corynebacterium pseudodiphtheriticum can eliminate S. aureus from the human nose. We sought to understand this phenomenon at a molecular level and found that C. pseudodiphtheriticum produces a factor(s) that specifically kills S. aureus. While resistant S. aureus isolates were recovered at a low frequency, resistance came at the cost of attenuated virulence in these strains. Molecular dissection of the specific strategies used by C. pseudodiphtheriticum to kill S. aureus could lead to the development of novel treatments or therapies. Furthermore, commensal competition that requires virulence components of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds. |
| first_indexed | 2024-12-18T23:26:47Z |
| format | Article |
| id | doaj.art-968300a93e7a46579ddf54584e4a47fb |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-18T23:26:47Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-968300a93e7a46579ddf54584e4a47fb2022-12-21T20:47:45ZengAmerican Society for MicrobiologymBio2150-75112019-02-0110110.1128/mBio.02491-18<named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense StrategyBritney L. Hardy0Seth W. Dickey1Roger D. Plaut2Daniel P. Riggins3Scott Stibitz4Michael Otto5D. Scott Merrell6F. Edward Hébert School of Medicine, Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USADivision of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USADivision of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USADivision of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USAF. Edward Hébert School of Medicine, Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USAABSTRACT Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest that microbial species-specific interactions can affect human nasal colonization by the opportunistic pathogen Staphylococcus aureus. However, the complex and dynamic molecular interactions that mediate these effects on S. aureus nasal colonization are often difficult to study and remain poorly understood. Here, we show that Corynebacterium pseudodiphtheriticum, a common member of the normal nasal microbiota, mediates contact-independent bactericidal activity against S. aureus, including methicillin-resistant S. aureus (MRSA). Bacterial interaction assays revealed that S. aureus isolates that were spontaneously resistant to C. pseudodiphtheriticum killing could be recovered at a low frequency. To better understand the pathways associated with killing and resistance, a S. aureus transposon mutant library was utilized to select for resistant mutant strains. We found that insertional inactivation of agrC, which codes for the sensor kinase of the Agr quorum sensing (Agr QS) system that regulates expression of many virulence factors in S. aureus, conferred resistance to killing. Analysis of the spontaneously resistant S. aureus isolates revealed that each showed decreased expression of the Agr QS components. Targeted analysis of pathways regulated by Agr QS revealed that loss of the phenol-soluble modulins (PSMs), which are effectors of Agr QS, also conferred resistance to bactericidal activity. Transmission electron microscopy analysis revealed that C. pseudodiphtheriticum induced dramatic changes to S. aureus cell surface morphology that likely resulted in cell lysis. Taken together, these data suggest that C. pseudodiphtheriticum-mediated killing of S. aureus requires S. aureus virulence components. While S. aureus can overcome targeted killing, this occurs at the cost of attenuated virulence; loss of Agr QS activity would phenotypically resemble a S. aureus commensal state that would be unlikely to be associated with disease. Commensal competition resulting in dampened virulence of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds. IMPORTANCE While some individuals are nasally colonized with S. aureus, the underlying factors that determine colonization are not understood. There is increasing evidence that indicates that resident bacteria play a role; some commensal species can eradicate S. aureus from the nasal cavity. Among these, Corynebacterium pseudodiphtheriticum can eliminate S. aureus from the human nose. We sought to understand this phenomenon at a molecular level and found that C. pseudodiphtheriticum produces a factor(s) that specifically kills S. aureus. While resistant S. aureus isolates were recovered at a low frequency, resistance came at the cost of attenuated virulence in these strains. Molecular dissection of the specific strategies used by C. pseudodiphtheriticum to kill S. aureus could lead to the development of novel treatments or therapies. Furthermore, commensal competition that requires virulence components of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds.https://journals.asm.org/doi/10.1128/mBio.02491-18commensal bacteriaCorynebacteriumnasal microbiotapolymicrobial interactionsStaphylococcus aureus |
| spellingShingle | Britney L. Hardy Seth W. Dickey Roger D. Plaut Daniel P. Riggins Scott Stibitz Michael Otto D. Scott Merrell <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy mBio commensal bacteria Corynebacterium nasal microbiota polymicrobial interactions Staphylococcus aureus |
| title | <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy |
| title_full | <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy |
| title_fullStr | <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy |
| title_full_unstemmed | <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy |
| title_short | <named-content content-type="genus-species">Corynebacterium pseudodiphtheriticum</named-content> Exploits <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Components in a Novel Polymicrobial Defense Strategy |
| title_sort | named content content type genus species corynebacterium pseudodiphtheriticum named content exploits named content content type genus species staphylococcus aureus named content virulence components in a novel polymicrobial defense strategy |
| topic | commensal bacteria Corynebacterium nasal microbiota polymicrobial interactions Staphylococcus aureus |
| url | https://journals.asm.org/doi/10.1128/mBio.02491-18 |
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