Proteomics

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FASII antibiotic adaptation reprograms Staphylococcus aureus behavior


ABSTRACT: Proving functionality in the host environment is a crucial step in antimicrobial development pipelines. Antibiotics targeting fatty acid synthesis (FASII) of the major pathogen Staphylococcus aureus actively inhibit FASII but do not prevent in vivo growth, as bacteria compensate the FASII block by using environmental fatty acids. We used proteomics and phosphoproteomics to elucidate S. aureus responses to anti-FASII in host-relevant conditions. S. aureus responded to anti-FASII treatment in serum by massive reprogramming. A striking inverse correlation was observed in anti-FASII-adapted S. aureus, between amounts of stress response proteins that increase, and virulence factors that decrease. These findings suggest that anti-FASII adapted cells might be better prepared for survival and less equipped to damage the host. Infection by anti-FASII-adapted versus non-treated S. aureus was challenged in the Galleria mellonella model. Time to mortality was longer in insects infected by anti-FASII-treated bacteria compared to those infected by non-treated S. aureus. However, bacterial counts in infected dead insects were comparable for both groups. These results support the hypothesis that higher stress response and lower virulence factor expression, as shown here in FASII-antibiotic-adapted bacteria, may set the stage for persistent infection

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Céline Henry  

LAB HEAD: Alexandra Gruss

PROVIDER: PXD034256 | Pride | 2023-10-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20180727_02_Saureus_1.mzXML Mzxml
20180727_02_Saureus_1.xml Xml
20180727_04_Saureus_4.mzXML Mzxml
20180727_04_Saureus_4.xml Xml
20180727_06_Saureus_6.mzXML Mzxml
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