A two-component system regulates hemin acquisition in Porphyromonas gingivalis

Area of Science:

• Microbiology
• Molecular Biology
• Genomics

Background:

• Porphyromonas gingivalis is a Gram-negative oral bacterium linked to periodontal disease.
• Two-component signal transduction systems regulate bacterial responses to environmental cues.
• Strain ATCC 33277 was identified as deficient in a specific histidine kinase (PGN_0752).

Purpose of the Study:

• To investigate the function of the PGN_0752/PGN_0753 two-component system in Porphyromonas gingivalis.
• To identify the genes regulated by this system, particularly those involved in hemin acquisition.
• To elucidate the regulatory mechanism, including activation and repression roles.

Main Methods:

• Comparative genome analysis of P. gingivalis strains W83 and ATCC 33277.
• Construction of a complemented strain of ATCC 33277 with functional PGN_0752.
• Microarray-based transcriptional profiling and ChIP-seq assays.
• Electrophoretic mobility shift assays (EMSA) to confirm direct DNA binding.

Main Results:

• The PGN_0752 histidine kinase and PGN_0753 response regulator form a functional two-component system.
• The regulon includes genes essential for hemin acquisition, such as gingipains and multiple transport systems.
• The system is self-regulated, with the response regulator acting as both an activator and repressor.
• Hemin was identified as a potential activator of the system.

Conclusions:

• The PGN_0752/PGN_0753 system is crucial for regulating hemin uptake and virulence in P. gingivalis.
• This signal transduction pathway provides a target for understanding and potentially controlling P. gingivalis infections.
• The findings highlight the importance of two-component systems in bacterial adaptation and pathogenesis.