Journal article

Authors list: Zhang, ZG; Wang, M; Zhang, Y; Zhang, YM; Bartkuhn, M; Markmann, M; Hossain, H; Chakraborty, T; Hake, SB; Jia, ZK; Meinhardt, A; Bhushan, S

Publication year: 2021

Pages: 1040-1051

Journal: The Journal of Infectious Diseases

Volume number: 223

Issue number: 6

ISSN: 0022-1899

DOI Link: https://doi.org/10.1093/infdis/jiab018

Publisher: Oxford University Press

Abstract: 
Urinary tract infections are common and costly diseases affecting millions of people. Uropathogenic Escherichia coli (UPEC) is a primary cause of these infections and has developed multiple strategies to avoid the host immune response. Here, we dissected the molecular mechanisms underpinning UPEC inhibition of inflammatory cytokine in vitro and in vivo. We found that UPEC infection simulates nuclear factor-kappa B activation but does not result in transcription of cytokine genes. Instead, UPEC-mediated suppression of the metabolic enzyme ATP citrate lyase results in decreased acetyl-CoA levels, leading to reduced H3K9 histone acetylation in the promotor region of CXCL8. These effects were dependent on the UPEC virulence factor alpha-hemolysin and were reversed by exogenous acetate. In a murine cystitis model, prior acetate supplementation rapidly resolved UPEC-elicited immune responses and improved tissue recovery. Thus, upon infection, UPEC rearranges host cell metabolism to induce chromatin remodeling processes that subvert expression of host innate immune response genes.

Harvard Citation style: Zhang, Z., Wang, M., Zhang, Y., Zhang, Y., Bartkuhn, M., Markmann, M., et al. (2021) Uropathogenic Escherichia coli Virulence Factor alpha-Hemolysin Reduces Histone Acetylation to Inhibit Expression of Proinflammatory Cytokine Genes, The Journal of Infectious Diseases, 223(6), pp. 1040-1051. https://doi.org/10.1093/infdis/jiab018

APA Citation style: Zhang, Z., Wang, M., Zhang, Y., Zhang, Y., Bartkuhn, M., Markmann, M., Hossain, H., Chakraborty, T., Hake, S., Jia, Z., Meinhardt, A., & Bhushan, S. (2021). Uropathogenic Escherichia coli Virulence Factor alpha-Hemolysin Reduces Histone Acetylation to Inhibit Expression of Proinflammatory Cytokine Genes. The Journal of Infectious Diseases. 223(6), 1040-1051. https://doi.org/10.1093/infdis/jiab018