TY - JOUR
T1 - Identification of Genes Regulating Cell Death in Staphylococcus aureus
AU - Yee, Rebecca
AU - Feng, Jie
AU - Wang, Jiou
AU - Chen, Jiazhen
AU - Zhang, Ying
N1 - Publisher Copyright:
© Copyright © 2019 Yee, Feng, Wang, Chen and Zhang.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Staphylococcus aureus
KW - cell death
KW - genes
KW - genetic screen
KW - mutants
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U2 - 10.3389/fmicb.2019.02199
DO - 10.3389/fmicb.2019.02199
M3 - Article
C2 - 31632363
AN - SCOPUS:85073670573
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 2199
ER -