Identification of Genes Regulating Cell Death in Staphylococcus aureus
Staphylococcus aureus is an opportunistic pathogen that causes acute and chronic infections. Due to S. aureus’s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicate S. aureus infections. Despite the efforts in understanding bacterial cell deat...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-10-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02199/full |
| _version_ | 1818431364746182656 |
|---|---|
| author | Rebecca Yee Jie Feng Jiou Wang Jiazhen Chen Ying Zhang |
| author_facet | Rebecca Yee Jie Feng Jiou Wang Jiazhen Chen Ying Zhang |
| author_sort | Rebecca Yee |
| collection | DOAJ |
| description | Staphylococcus aureus is an opportunistic pathogen that causes acute and chronic infections. Due to S. aureus’s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicate S. aureus infections. Despite the efforts in understanding bacterial cell death, the genes, and pathways of S. aureus cell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved in S. aureus cell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid, and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in 10 core genes (capA, gltT, mnhG1, USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, and cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in a Caenorhabditis elegans infection model. Conversely, death-sensitive mutants were less persistent and formed fewer persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms of S. aureus cell death and offer new therapeutic targets for developing more effective treatments for infections caused by S. aureus. |
| first_indexed | 2024-12-14T15:48:08Z |
| format | Article |
| id | doaj.art-012e4f080f344476ac459b36c34d80e1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T15:48:08Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-012e4f080f344476ac459b36c34d80e12022-12-21T22:55:26ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-10-011010.3389/fmicb.2019.02199480608Identification of Genes Regulating Cell Death in Staphylococcus aureusRebecca Yee0Jie Feng1Jiou Wang2Jiazhen Chen3Ying Zhang4Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesStaphylococcus aureus is an opportunistic pathogen that causes acute and chronic infections. Due to S. aureus’s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicate S. aureus infections. Despite the efforts in understanding bacterial cell death, the genes, and pathways of S. aureus cell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved in S. aureus cell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid, and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in 10 core genes (capA, gltT, mnhG1, USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, and cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in a Caenorhabditis elegans infection model. Conversely, death-sensitive mutants were less persistent and formed fewer persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms of S. aureus cell death and offer new therapeutic targets for developing more effective treatments for infections caused by S. aureus.https://www.frontiersin.org/article/10.3389/fmicb.2019.02199/fullStaphylococcus aureuscell deathgenetic screenmutantsgenes |
| spellingShingle | Rebecca Yee Jie Feng Jiou Wang Jiazhen Chen Ying Zhang Identification of Genes Regulating Cell Death in Staphylococcus aureus Frontiers in Microbiology Staphylococcus aureus cell death genetic screen mutants genes |
| title | Identification of Genes Regulating Cell Death in Staphylococcus aureus |
| title_full | Identification of Genes Regulating Cell Death in Staphylococcus aureus |
| title_fullStr | Identification of Genes Regulating Cell Death in Staphylococcus aureus |
| title_full_unstemmed | Identification of Genes Regulating Cell Death in Staphylococcus aureus |
| title_short | Identification of Genes Regulating Cell Death in Staphylococcus aureus |
| title_sort | identification of genes regulating cell death in staphylococcus aureus |
| topic | Staphylococcus aureus cell death genetic screen mutants genes |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02199/full |
| work_keys_str_mv | AT rebeccayee identificationofgenesregulatingcelldeathinstaphylococcusaureus AT jiefeng identificationofgenesregulatingcelldeathinstaphylococcusaureus AT jiouwang identificationofgenesregulatingcelldeathinstaphylococcusaureus AT jiazhenchen identificationofgenesregulatingcelldeathinstaphylococcusaureus AT yingzhang identificationofgenesregulatingcelldeathinstaphylococcusaureus |