Persistent peripheral presence of Staphylococcus aureus promotes histone H3 hypoacetylation and decreases tyrosine hydroxylase protein level in rat brain tissues
Autor: | Arnab Choudhury, Bhawna Solanki, Upasana Sahu, Surajit Ganguly, Suhel Parvez, Seema Singh, Sudeshna Kar |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Staphylococcus aureus Tyrosine 3-Monooxygenase Hippocampus Gene Expression Biology medicine.disease_cause Histone Deacetylases Histones 03 medical and health sciences Histone H3 0302 clinical medicine medicine Escherichia coli Animals Epigenetics Rats Wistar Prefrontal cortex Promoter Regions Genetic Tyrosine hydroxylase General Neuroscience Brain Acetylation Molecular biology 030104 developmental biology 030217 neurology & neurosurgery Homeostasis |
Zdroj: | Neuroreport. 30(16) |
ISSN: | 1473-558X |
Popis: | Objective Growing evidences suggest systemic pathogen-induced neuroimmune interaction is a major risk factor for several neurological disorders. Our goal was to investigate whether asymptomatic peripheral carriage of Staphylococcus aureus, a widespread opportunistic pathogen, could modulate selective molecular features in brain tissues. Methods To address this, a peripheral infection model was developed by challenging Wistar rats repeatedly with a clinical strain of S. aureus. Animals infected with S. aureus (10 CFU for three times in 10 days) showed significant changes in acetylation profile of selective lysine (K) residues K9 (H3K9), K14 (H3K14) and K27 (H3K27) of histone H3 in the hippocampus and prefrontal cortex (PFC). Results Although S. aureus was restricted peripherally, the infection induced hypoacetylation of H3K9, H3K14 and H3K27 in the hippocampus and H3K27 in the PFC. Histone H3 hypoacetylation in the hippocampus and PFC was also detected when rats were challenged with an engineered invasive strain of E. coli K12, SK3842. This confirmed that modulation of epigenetic landscape in distal brain tissues may not be specific to S. aureus. Moreover, the tyrosine hydroxylase protein, the rate limiting enzyme in dopamine synthesis pathway whose gene-expression is regulated by H3 acetylation at the promoter, was remarkably reduced in the brain tissues of the infected hosts. Conclusion The results indicate that commensals like S. aureus, in spite of being largely restricted to the peripheral tissues, could modulate the homeostasis of molecular features in brain tissues whose maintenance is critical for preserving normal neurological functions. |
Databáze: | OpenAIRE |
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