Anti-Sense Antibiotic Agents as Treatment for Bacterial Infections.

Background: Conventional antibiotic agents are overused, leading to decreased efficacy because of a rising incidence in antimicrobial resistance. Further, conventional antibiotic agents result in widespread effects to human microbiota, which can lead directly to adverse events such as Clostridium difficile infection.
Methods: This review provides a narrative summary of anti-sense therapies, an approach to managing bacterial infections by pursuing specific molecular targets that disrupt the flow of information from deoxyribonucleic acid to ribonucleic acid to protein, leading to the loss of bacterial functions. Included in this article is the rationale for this approach, the current data supporting its further investigation, and the challenges and future directions in this area of research.
Results: There is a compelling proof-of-concept against both gram-positive and gram-negative organisms to commend the use of modified anti-sense oligonucleotides as antimicrobial therapy. There are data demonstrating that anti-sense therapies are capable of killing bacteria, silencing antimicrobial resistance mechanisms to restore sensitivity to conventional antibiotic agents, and to target virulence pathways such as biofilm production. Further, these drugs have a significantly greater degree of organismal specificity, limiting antibiotic-associated diarrhea and lowering the risk of antibiotic-related infections such as C. difficile infection. Conclusions: Anti-sense therapies show promise as a new class of antibiotic agents, providing molecular precision that leads to specific targeting of bacterial species and bacterial functions, including virulence mechanisms beyond the reach of current antibiotic agents. Further, changing the sequence of an anti-sense oligonucleotide provides a method of dealing with antimicrobial resistance that is more time- and cost-flexible than the available options with current conventional antibiotic agents.