Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 24:12:977944.
doi: 10.3389/fcimb.2022.977944. eCollection 2022.

Two-component regulatory systems in Helicobacter pylori and Campylobacter jejuni: Attractive targets for novel antibacterial drugs

Javier Casado  1   2 , Ángel Lanas  1   3   4   5 , Andrés González  1   3   4
Affiliations
Review

Two-component regulatory systems in Helicobacter pylori and Campylobacter jejuni: Attractive targets for novel antibacterial drugs

Javier Casado et al. Front Cell Infect Microbiol. .

Abstract

Two-component regulatory systems (TCRS) are ubiquitous signal transduction mechanisms evolved by bacteria for sensing and adapting to the constant changes that occur in their environment. Typically consisting of two types of proteins, a membrane sensor kinase and an effector cytosolic response regulator, the TCRS modulate via transcriptional regulation a plethora of key physiological processes, thereby becoming essential for bacterial viability and/or pathogenicity and making them attractive targets for novel antibacterial drugs. Some members of the phylum Campylobacterota (formerly Epsilonproteobacteria), including Helicobacter pylori and Campylobacter jejuni, have been classified by WHO as "high priority pathogens" for research and development of new antimicrobials due to the rapid emergence and dissemination of resistance mechanisms against first-line antibiotics and the alarming increase of multidrug-resistant strains worldwide. Notably, these clinically relevant pathogens express a variety of TCRS and orphan response regulators, sometimes unique among its phylum, that control transcription, translation, energy metabolism and redox homeostasis, as well as the expression of relevant enzymes and virulence factors. In the present mini-review, we describe the signalling mechanisms and functional diversity of TCRS in H. pylori and C. jejuni, and provide an overview of the most recent findings in the use of these microbial molecules as potential novel therapeutic targets for the development of new antibiotics.

Keywords: Campylobacter jejuni; Campylobacterota; Epsilonproteobacteria; Helicobacter pylori; orphan response regulator; therapeutic target; two-component regulatory system.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Bacterial two-component regulatory systems (TCRS). (A) Schematic representation of a typical TCRS comprising a membrane-anchored sensor histidine kinase (HK) and its cognate cytoplasmic response regulator (RR). Although microbial HKs can exhibit a considerable variety in their architectures (Jacob-Dubuisson et al., 2018), a canonical HK consists in a multi-domain homodimeric protein with extracellular sensors that perceives specific stimuli and undergoes autophosphorylation in a conserved His residue through a cytosolic catalytic-ATP binding domain. Phosphoryl group is subsequently transferred to a conserved Asp residue of the cognate RR promoted mainly by intermolecular interactions between the dimerization and histidine phosphotransfer (DHp) domains of the HK and the receiver (REC) domain of the RR (Yamada et al., 2009). Thus, the specificity of the interaction between a given HK and its cognate RR appears to be primarily defined by the nature and positions of contacting residues at the interface between the DHp (HK) and the REC (RR) domains, though additional HK domains could also be involved in RR binding (Buschiazzo and Trajtenberg, 2019). (B) 3D structures of different HK- and RR-functional domains. Corresponding Protein Data Bank (PDB) entries appear in parentheses.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Acio-Pizzarello C. R., Acio A. A., Choi E. J., Bond K., Kim J., Kenan A. C., et al. . (2017). Determinants of the regulation of Helicobacter pylori adhesins include repeat sequences in both promoter and coding regions as well as the two-component system ArsRS. J. Med. Microbiol. 66 (6), 798–807. doi: 10.1099/jmm.0.000491 - DOI - PubMed
    1. Alvarado A., Behrens W., Josenhans C. (2019). Protein activity sensing in bacteria in regulating metabolism and motility. Front. Microbiol. 10. doi: 10.3389/fmicb.2019.03055 - DOI - PMC - PubMed
    1. Antoniciello F., Roncarati D., Zannoni A., Chiti E., Scarlato V., Chiappori F. (2022). Targeting the essential transcription factor HP1043 of Helicobacter pylori: a drug repositioning study. Front. Mol. Biosci. 9. doi: 10.3389/fmolb.2022.887564 - DOI - PMC - PubMed
    1. Apel D., Ellermeier J., Pryjma M., Dirita V. J., Gaynor E. C. (2012). Characterization of Campylobacter jejuni RacRS reveals roles in the heat shock response, motility, and maintenance of cell length homogeneity. J. Bacteriol 194 (9), 2342–2354. doi: 10.1128/JB.06041-11 - DOI - PMC - PubMed
    1. Arguello E., Otto C. C., Mead P., Babady N. E. (2015). Bacteremia caused by Arcobacter butzleri in an immunocompromised host. J. Clin. Microbiol. 53 (4), 1448–1451. doi: 10.1128/JCM.03450-14 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources