Key Points
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Gram-negative and Gram-positive pathogens use a common virulence strategy to increase the expression of Kruppel-like factor mammalian transcriptional regulators.
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This strategy involves the subversion of host cell functions by secreting bacterial exotoxins using a type III secretion system or an alternative secretion mechanism.
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Exploitation of the Kruppel-like factor regulatory cascade results in the modulation of numerous cell processes, including NFκB activation, pro-inflammatory cytokine expression, actin cytoskeletal dynamics, cell proliferation and phagocytosis.
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The modulation of Kruppel-like factors 2 and 6 by diverse pathogens such as Pseudomonas aeruginosa, Yersinia enterocolitica, Clostridium botulinum and Staphylococcus aureus could involve a common mechanism based on altered activities of the Rho protein signalling cascade.
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Increased expression of KLF2 by bacterial pathogens may be due to relief from repression of KLF2 by Rho-GTP, which may or may not involve NFκB, itself a negative regulator of KLF2 expression.
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Analysis of the modular structure of the bacterial effector proteins indicates that enzymatic substrate specificity has an important role in the alteration of these transcriptional regulators.
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Increased expression of Kruppel-like factors 2 and/or 6, as is seen in response to bacterial infection would result in decreased expression of NFκB and JUN, inhibition of phagocytosis, pro-inflammatory cytokines and cellular proliferation, ultimately to the detriment of the host.
Abstract
Diverse pathogenic bacteria have developed similar mechanisms to subvert host cell responses. In this Progress article, we focus on bacterial virulence factors with different enzymatic activities that can increase the expression of the Kruppel-like factor (KLF) family of mammalian transcriptional regulators through their ability to modify the activity of a common host-cell target — the Rho protein family. By using a common virulence strategy, both Gram-negative and Gram-positive pathogens exploit the KLF regulatory cascade to modulate nuclear factor κB activation, pro-inflammatory cytokine expression, actin cytoskeletal dynamics and phagocytosis.
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Acknowledgements
This work was supported in part by grants awarded by the Higher Education Authority of Ireland (PRTLI programme), the Science Foundation of Ireland, the European Commission and the Health Research Board.
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O'Grady, E., Mulcahy, H., Adams, C. et al. Manipulation of host Kruppel-like factor (KLF) function by exotoxins from diverse bacterial pathogens. Nat Rev Microbiol 5, 337–341 (2007). https://doi.org/10.1038/nrmicro1641
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DOI: https://doi.org/10.1038/nrmicro1641
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