ArticleJournal of bacteriology2013
Activation of CpxRA in Haemophilus ducreyi primarily inhibits the expression of its targets, including major virulence determinants.
Article in Journal of bacteriology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Molecular pathogenesis ofMicrobiology and molecular biology reviews : MMBR · 2025Review
- Regulatory role of the Cpx ESR in bacterial behaviours.Virulence · 2024Review
- Cpx-signalling innpj antimicrobials and resistance · 2024Article
- CpxA Phosphatase Inhibitor Activates CpxRA and Is a Potential Treatment for Uropathogenic Escherichia coli in a Murine Model of Infection.Microbiology spectrum · 2022Article
- Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria.Frontiers in cellular and infection microbiology · 2019Review
- Evaluation of CpxRA as a Therapeutic Target for Uropathogenic Escherichia coli Infections.Infection and immunity · 2018Article
- A Bacterial Stress Response Regulates Respiratory Protein Complexes To Control Envelope Stress Adaptation.Journal of bacteriology · 2017Article
- Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection.Infection and immunity · 2017Article
- Haemophilus ducreyi Seeks Alternative Carbon Sources and Adapts to Nutrient Stress and Anaerobiosis during Experimental Infection of Human Volunteers.Infection and immunity · 2016Article
- Environmental Regulation of Yersinia Pathophysiology.Frontiers in cellular and infection microbiology · 2016Review
- DksA and (p)ppGpp have unique and overlapping contributions to Haemophilus ducreyi pathogenesis in humans.Infection and immunity · 2015Article
- Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system.Antimicrobial agents and chemotherapy · 2015Article
- The Cpx system regulates virulence gene expression in Vibrio cholerae.Infection and immunity · 2015Article
- The CpxRA two-component system is essential for Citrobacter rodentium virulence.Infection and immunity · 2015Article
- Validation of reference genes for quantitative real-time PCR (qPCR) analysis of Actinobacillus suis.BMC research notes · 2015Article
- The Cpx envelope stress response modifies peptidoglycan cross-linking via the L,D-transpeptidase LdtD and the novel protein YgaU.Journal of bacteriology · 2015Article
- The Vibrio cholerae Cpx envelope stress response senses and mediates adaptation to low iron.Journal of bacteriology · 2015Article
- Haemophilus ducreyi RpoE and CpxRA appear to play distinct yet complementary roles in regulation of envelope-related functions.Journal of bacteriology · 2014Article
- Reciprocal regulation of resistance-nodulation-division efflux systems and the Cpx two-component system in Vibrio cholerae.Infection and immunity · 2014Article
- Haemophilus ducreyi Hfq contributes to virulence gene regulation as cells enter stationary phase.mBio · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
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