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Acyl Homoserine Lactone Sensitised Streptococcus Pyogenes Differentially Regulates the Transcriptional Expression of Early Growth Response 1 (EGR1) in Epithelial and Macrophage Cells

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Abstract

The host transcriptional activator Early growth response 1 (EGR1) plays a vital role in cell cycle and differentiation, cell proliferation, and regulation of cytokines and several growth factors. It is an immediate-early gene that is expressed as an initial response to various environmental stimuli. Bacterial infection is one such factor that can trigger the expression of EGR1 in host. Therefore, it is imperative to understand expression of EGR1 during early stages of host-pathogen interaction. Streptococcus pyogenes is an opportunistic bacteria causing skin and respiratory tract infections in humans. The quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (Oxo-C12), not synthesised by S. pyogenes, can be sensed by S. pyogenes leading to molecular changes in the pathogen. In this study, we investigated the role of Oxo-C12 on EGR1 regulation in lung epithelial and murine macrophage cell line upon S. pyogenes infection. We report that Oxo-C12 sensitised S. pyogenes upregulates the transcriptional expression of EGR1 through ERK1/2 pathway. It was observed that EGR1 was not involved in the intial attachment of S. pyogenes to A549 cells. However, inhibition of EGR1 in macrophage cell line, J774A.1, through the ERK1/2 pathway resulted in decreased adhesion of S. pyogenes. The EGR1 upregulation by Oxo-C12 sensitised S. pyogenes plays a vital role in enhancing the survival of S. pyogenes in murine macrophages, leading to persistent infection. Thus, understanding the molecular modulation in the host during bacterial infection will further help develop therapeutics to target specific sites.

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Acknowledgements

We would like to thank the support of Symbiosis Centre for Research and Innovation for their support through the research fellowship programs.

Funding

RB is supported by the senior research fellowship program of the Symbiosis International (Deemed University). RJ is supported by the ERASMUS + grant. The work was supported by the Ramalingaswami fellowship program of Department of Biotechnology, India under grant BT/RLF/Re-entry/41/2015.

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  1. Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Symbiosis Knowledge Village, Lavale, Maharashtra, 412115, Pune, India

    Rajashri Banerji, Riya Joshi & Sunil D. Saroj

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  1. Rajashri Banerji
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  2. Riya Joshi
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  3. Sunil D. Saroj
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SD conceptualised the idea. RB and RJ performed the experiments. RB analysed the data and prepared the manuscript. SD and RB finalised the draft.

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Correspondence to Sunil D. Saroj.

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Banerji, R., Joshi, R. & Saroj, S.D. Acyl Homoserine Lactone Sensitised Streptococcus Pyogenes Differentially Regulates the Transcriptional Expression of Early Growth Response 1 (EGR1) in Epithelial and Macrophage Cells. Curr Microbiol 80, 268 (2023). https://doi.org/10.1007/s00284-023-03375-0

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