The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation
ABSTRACT Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. A. baumannii is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell...
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-06-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01254-20 |
| _version_ | 1818900664189714432 |
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| author | Brenna J. C. Walsh Jiefei Wang Katherine A. Edmonds Lauren D. Palmer Yixiang Zhang Jonathan C. Trinidad Eric P. Skaar David P. Giedroc |
| author_facet | Brenna J. C. Walsh Jiefei Wang Katherine A. Edmonds Lauren D. Palmer Yixiang Zhang Jonathan C. Trinidad Eric P. Skaar David P. Giedroc |
| author_sort | Brenna J. C. Walsh |
| collection | DOAJ |
| description | ABSTRACT Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. A. baumannii is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell surfaces. Here, we investigate the response of A. baumannii toward sodium sulfide (Na2S), known to be associated with some biofilms at oxic/anoxic interfaces. The addition of exogenous inorganic sulfide reveals that A. baumannii encodes two persulfide-sensing transcriptional regulators, a primary σ54-dependent transcriptional activator (FisR), and a secondary system controlled by the persulfide-sensing biofilm growth-associated repressor (BigR), which is only induced by sulfide in a fisR deletion strain. FisR activates an operon encoding a sulfide oxidation/detoxification system similar to that characterized previously in Staphylococcus aureus, while BigR regulates a secondary persulfide dioxygenase (PDO2) as part of yeeE-yedE-pdo2 sulfur detoxification operon, found previously in Serratia spp. Global S-sulfuration (persulfidation) mapping of the soluble proteome reveals 513 persulfidation targets well beyond FisR-regulated genes and includes five transcriptional regulators, most notably the master biofilm regulator BfmR and a poorly characterized catabolite regulatory protein (Crp). Both BfmR and Crp are well known to impact biofilm formation in A. baumannii and other organisms, respectively, suggesting that persulfidation of these regulators may control their activities. The implications of these findings on bacterial sulfide homeostasis, persulfide signaling, and biofilm formation are discussed. IMPORTANCE Although hydrogen sulfide (H2S) has long been known as a respiratory poison, recent reports in numerous bacterial pathogens reveal that H2S and more downstream oxidized forms of sulfur collectedly termed reactive sulfur species (RSS) function as antioxidants to combat host efforts to clear the infection. Here, we present a comprehensive analysis of the transcriptional and proteomic response of A. baumannii to exogenous sulfide as a model for how this important human pathogen manages sulfide/RSS homeostasis. We show that A. baumannii is unique in that it encodes two independent persulfide sensing and detoxification pathways that govern the speciation of bioactive sulfur in cells. The secondary persulfide sensor, BigR, impacts the expression of biofilm-associated genes; in addition, we identify two other transcriptional regulators known or projected to regulate biofilm formation, BfmR and Crp, as highly persulfidated in sulfide-exposed cells. These findings significantly strengthen the connection between sulfide homeostasis and biofilm formation in an important human pathogen. |
| first_indexed | 2024-12-19T20:07:27Z |
| format | Article |
| id | doaj.art-9c05a8f948d04b15b84e77a4280b07b8 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T20:07:27Z |
| publishDate | 2020-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-9c05a8f948d04b15b84e77a4280b07b82022-12-21T20:07:26ZengAmerican Society for MicrobiologymBio2150-75112020-06-0111310.1128/mBio.01254-20The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm RegulationBrenna J. C. Walsh0Jiefei Wang1Katherine A. Edmonds2Lauren D. Palmer3Yixiang Zhang4Jonathan C. Trinidad5Eric P. Skaar6David P. Giedroc7Department of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Pathology, Microbiology and Immunology, and Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USALaboratory for Biological Mass Spectrometry, Indiana University, Bloomington, Indiana, USALaboratory for Biological Mass Spectrometry, Indiana University, Bloomington, Indiana, USADepartment of Pathology, Microbiology and Immunology, and Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USAABSTRACT Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. A. baumannii is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell surfaces. Here, we investigate the response of A. baumannii toward sodium sulfide (Na2S), known to be associated with some biofilms at oxic/anoxic interfaces. The addition of exogenous inorganic sulfide reveals that A. baumannii encodes two persulfide-sensing transcriptional regulators, a primary σ54-dependent transcriptional activator (FisR), and a secondary system controlled by the persulfide-sensing biofilm growth-associated repressor (BigR), which is only induced by sulfide in a fisR deletion strain. FisR activates an operon encoding a sulfide oxidation/detoxification system similar to that characterized previously in Staphylococcus aureus, while BigR regulates a secondary persulfide dioxygenase (PDO2) as part of yeeE-yedE-pdo2 sulfur detoxification operon, found previously in Serratia spp. Global S-sulfuration (persulfidation) mapping of the soluble proteome reveals 513 persulfidation targets well beyond FisR-regulated genes and includes five transcriptional regulators, most notably the master biofilm regulator BfmR and a poorly characterized catabolite regulatory protein (Crp). Both BfmR and Crp are well known to impact biofilm formation in A. baumannii and other organisms, respectively, suggesting that persulfidation of these regulators may control their activities. The implications of these findings on bacterial sulfide homeostasis, persulfide signaling, and biofilm formation are discussed. IMPORTANCE Although hydrogen sulfide (H2S) has long been known as a respiratory poison, recent reports in numerous bacterial pathogens reveal that H2S and more downstream oxidized forms of sulfur collectedly termed reactive sulfur species (RSS) function as antioxidants to combat host efforts to clear the infection. Here, we present a comprehensive analysis of the transcriptional and proteomic response of A. baumannii to exogenous sulfide as a model for how this important human pathogen manages sulfide/RSS homeostasis. We show that A. baumannii is unique in that it encodes two independent persulfide sensing and detoxification pathways that govern the speciation of bioactive sulfur in cells. The secondary persulfide sensor, BigR, impacts the expression of biofilm-associated genes; in addition, we identify two other transcriptional regulators known or projected to regulate biofilm formation, BfmR and Crp, as highly persulfidated in sulfide-exposed cells. These findings significantly strengthen the connection between sulfide homeostasis and biofilm formation in an important human pathogen.https://journals.asm.org/doi/10.1128/mBio.01254-20Acinetobacter baumanniihydrogen sulfidereactive sulfur speciesprotein S-sulfurationpersulfidepersulfidation |
| spellingShingle | Brenna J. C. Walsh Jiefei Wang Katherine A. Edmonds Lauren D. Palmer Yixiang Zhang Jonathan C. Trinidad Eric P. Skaar David P. Giedroc The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation mBio Acinetobacter baumannii hydrogen sulfide reactive sulfur species protein S-sulfuration persulfide persulfidation |
| title | The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation |
| title_full | The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation |
| title_fullStr | The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation |
| title_full_unstemmed | The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation |
| title_short | The Response of <italic toggle="yes">Acinetobacter baumannii</italic> to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation |
| title_sort | response of italic toggle yes acinetobacter baumannii italic to hydrogen sulfide reveals two independent persulfide sensing systems and a connection to biofilm regulation |
| topic | Acinetobacter baumannii hydrogen sulfide reactive sulfur species protein S-sulfuration persulfide persulfidation |
| url | https://journals.asm.org/doi/10.1128/mBio.01254-20 |
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