Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxin...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2016-11-01
|
| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01579-16 |
| _version_ | 1818822503670218752 |
|---|---|
| author | Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto |
| author_facet | Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto |
| author_sort | Hwang-Soo Joo |
| collection | DOAJ |
| description | ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production. IMPORTANCE Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection. |
| first_indexed | 2024-12-18T23:25:07Z |
| format | Article |
| id | doaj.art-61c33f922bf24eabbaba5dfb4d68f5fc |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-18T23:25:07Z |
| publishDate | 2016-11-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-61c33f922bf24eabbaba5dfb4d68f5fc2022-12-21T20:47:49ZengAmerican Society for MicrobiologymBio2150-75112016-11-017510.1128/mBio.01579-16Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> ToxinHwang-Soo Joo0Som S. Chatterjee1Amer E. Villaruz2Seth W. Dickey3Vee Y. Tan4Yan Chen5Daniel E. Sturdevant6Stacy M. Ricklefs7Michael Otto8Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAGenomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAGenomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USAPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production. IMPORTANCE Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.https://journals.asm.org/doi/10.1128/mBio.01579-16 |
| spellingShingle | Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin mBio |
| title | Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin |
| title_full | Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin |
| title_fullStr | Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin |
| title_full_unstemmed | Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin |
| title_short | Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin |
| title_sort | mechanism of gene regulation by a named content content type genus species staphylococcus aureus named content toxin |
| url | https://journals.asm.org/doi/10.1128/mBio.01579-16 |
| work_keys_str_mv | AT hwangsoojoo mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT somschatterjee mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT amerevillaruz mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT sethwdickey mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT veeytan mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT yanchen mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT danielesturdevant mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT stacymricklefs mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin AT michaelotto mechanismofgeneregulationbyanamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontenttoxin |