Sensing the Messenger: Potential Roles of Cyclic-di-GMP in Rickettsial Pathogenesis.

Area of Science:

• Microbiology
• Molecular Biology
• Immunology

Background:

• Rickettsioses are bacterial infections transmitted by arthropods, primarily affecting vascular endothelial cells.
• Bacterial cyclic-di-GMP (c-di-GMP) is a second messenger involved in bacterial communication and host interactions, but its role in rickettsial pathogenesis is unknown.

Purpose of the Study:

• To investigate the presence and potential role of c-di-GMP in pathogenic rickettsiae.
• To analyze the genetic variability of the c-di-GMP synthesizing enzyme, PleD, across different Rickettsia strains.
• To assess the impact of Rickettsia infection on PleD levels in host cells.

Main Methods:

• Bioinformatic analysis of rickettsial genomes to identify the c-di-GMP synthesizing gene (pleD).
• Cloning and sequencing of the pleD gene from virulent and avirulent Rickettsia rickettsii strains.
• In vitro infection of human microvascular endothelial cells (HMECs) with Rickettsia strains and measurement of pleD levels.

Main Results:

• All rickettsial genomes encode a putative c-di-GMP synthesizing enzyme, PleD, with conserved domain architecture but sequence variations.
• A nonsynonymous substitution was identified in the pleD gene between virulent and avirulent R. rickettsii strains.
• Infection with virulent R. rickettsii (Sheila Smith) caused dynamic changes in pleD levels in HMECs, unlike the avirulent strain (Iowa).

Conclusions:

• This study provides the first evidence for the involvement of c-di-GMP in host-cell responses to pathogenic rickettsiae.
• Variations in rickettsial pleD and its impact on host cells suggest a role for c-di-GMP in rickettsial virulence and pathogenesis.
• Further research into the molecular mechanisms of c-di-GMP in rickettsiosis is warranted.