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Activation of CpxRA in Haemophilus ducreyi Primarily Inhibits the Expression of Its Targets, Including Major Virulence Determinants

Gangaiah, D. ; Zhang, X. ; Fortney, K. R. ; Baker, B. ; Liu, Y. ; Munson, R. S. ; Spinola, S. M.

Journal of Bacteriology, 08/01/2013, Vol.195(15), pp.3486-3502 [Periódico revisado por pares]

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  • Título:
    Activation of CpxRA in Haemophilus ducreyi Primarily Inhibits the Expression of Its Targets, Including Major Virulence Determinants
  • Autor: Gangaiah, D. ; Zhang, X. ; Fortney, K. R. ; Baker, B. ; Liu, Y. ; Munson, R. S. ; Spinola, S. M.
  • Assuntos: Phagocytes ; Operon ; Bacteria ; Human Immunodeficiency Virus 1 ; Virulence ; Pathogenesis ; Humans ; Signal Transduction ; Gene Expression Regulation ; Mutants ; Haemophilus Ducreyi
  • É parte de: Journal of Bacteriology, 08/01/2013, Vol.195(15), pp.3486-3502
  • Descrição: Haemophilus ducreyi causes chancroid, a genital ulcer disease that facilitates the transmission of human immunodeficiency virus type 1. In humans, H. ducreyi is surrounded by phagocytes and must adapt to a hostile environment to survive. To sense and respond to environmental cues, bacteria frequently use two-component signal transduction (2CST) systems. The only obvious 2CST system in H. ducreyi is CpxRA; CpxR is a response regulator, and CpxA is a sensor kinase. Previous studies by Hansen and coworkers showed that CpxR directly represses the expression of dsrA, the lspB-lspA2 operon, and the flp operon, which are required for virulence in humans. They further showed that CpxA functions predominantly as a phosphatase in vitro to maintain the expression of virulence determinants. Since a cpxA mutant is avirulent while a cpxR mutant is fully virulent in humans, CpxA also likely functions predominantly as a phosphatase in vivo. To better understand the role of H. ducreyi CpxRA in controlling virulence determinants, here we defined genes potentially regulated by CpxRA by using RNA-Seq. Activation of CpxR by deletion of cpxA repressed nearly 70% of its targets, including seven established virulence determinants. Inactivation of CpxR by deletion of cpxR differentially regulated few genes and increased the expression of one virulence determinant. We identified a CpxR binding motif that was enriched in downregulated but not upregulated targets. These data reinforce the hypothesis that CpxA phosphatase activity plays a critical role in controlling H. ducreyi virulence in vivo. Characterization of the downregulated genes may offer new insights into pathogenesis. ; p. 3486-3502.
  • Idioma: Inglês

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