Small interfering RNAs targeting agrA and sarA attenuate pathogenesis of Staphylococcus aureus in Caenorhabditis elegans
Introduction: The use of small interfering RNA (siRNA) gene silencing is a promising therapeutic option as it does not impose selective pressure on bacteria that is often associated with the development of resistance. The study assessed the effect of siRNA targeted to sarA and agrA in S. aureus and the relationship between the transcriptional response, biofilm formation and pathogenicity.
Methodology: siRNAs designed against agrA and sarA were electroporated into methicillin-resistant and methicillin-susceptible S. aureus strains. mRNA levels, growth kinetics, biofilm formation and minimal inhibitory concentration were measured. Efficacy of siRNA in bacteria was assessed using survival assays in a C. elegans model. Differences in gene expression before and after siRNA treatment were anaysed using the paired t-test, while the log rank test was used to assess the significance of any difference among survival rates of nematodes.
Results: Biofilm formation decreased significantly in siRNA treated strains and growth rates of siRNA treated strains were significantly higher compared to untreated strains. We observed significant decreases in the transcriptional response in siRNA treated strains, with concomitant significant increases in the lifespan of C. elegans worms exposed to siRNA-treated versus untreated strains.
Conclusions: siRNA targeted to agrA and sarA lowered mRNA transcription and pathogenicity of S. aureus.
Copyright (c) 2021 Terissa Alexas Thompson, Paul Dean Brown
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).