title: Epigenetic response in mice mastitis: Role of histone H3 acetylation and microRNA(s) in the regulation of host inflammatory gene expression during Staphylococcus aureus infection.
abstract: BACKGROUND
  There is renewed interest towards understanding the host-pathogen interaction in the light of epigenetic modifications. Although epithelial tissue is the major site for host-pathogen interactions, there is handful of studies to show how epithelial cells respond to pathogens. Bacterial infection in the mammary gland parenchyma induces local and subsequently systemic inflammation that results in a complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection.
  
  
  RESULTS
  In the present report we have addressed the differential inflammatory response in mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus, isolated from field samples. Immunohistochemical and immunoblotting analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Global gene expression analysis in S. aureus infected mice mammary tissue revealed a selective set of upregulated genes that significantly correlated with the promoter specific, histone H3K14 acetylation. Furthermore, we have identified several differentially expressed known miRNAs and 3 novel miRNAs in S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NF-κB signaling leading to drastic inflammatory response and induction of immune surveillance, which could possibly lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue.
  
  
  CONCLUSIONS
  Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. In a broader perspective this study also paves the way to understand how certain bacteria can evade the immune surveillance and cause sustained infection while others are rapidly cleared from the host body.
authors: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560064, India.|School of Biotechnology, Kalinga Institute of Industrial Technology, Campus XI, Patia, Bhubaneswar 751024, India.
authors: Rahul
authors: R
authors: Modak
authors: Project Directorate on Animal Disease Monitoring and Surveillance, Bangalore, India.|Department of Biotechnology, Assam University, Silchar 788011, India.
authors: Susweta
authors: S
authors: Das Mitra
authors: Bionivid Technology [P] Ltd, 401 - 4 AB Cross, 1st Main, Kasturi Nagar, East of NGEF, Bangalore 560043, India.
authors: Madavan
authors: M
authors: Vasudevan
authors: Project Directorate on Animal Disease Monitoring and Surveillance, Bangalore, India.
authors: Paramanandhan
authors: P
authors: Krishnamoorthy
authors: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560064, India.
authors: Manoj
authors: M
authors: Kumar
authors: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560064, India.
authors: Akshay V
authors: AV
authors: Bhat
authors: Project Directorate on Animal Disease Monitoring and Surveillance, Bangalore, India.|Department of Biochemistry, Veterinary College and Research Institute, Namakkal 637002, India.
authors: Mani
authors: M
authors: Bhuvana
authors: Department of Biotechnology, Assam University, Silchar 788011, India.
authors: Sankar K
authors: SK
authors: Ghosh
authors: Project Directorate on Animal Disease Monitoring and Surveillance, Bangalore, India.
authors: Bibek R
authors: BR
authors: Shome
authors: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O, Bangalore 560064, India.
authors: Tapas K
authors: TK
authors: Kundu
keywords: Acetylation; Chromatin immunoprecipitation; Epigenetic modifications; Gene expression; Histone; Inflammatory response; Mastitis; Micro-RNA; S. aureus infection