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Author Spotlight: Efficiently Eliminating Bacteriophages from Infected Salmonella Cultures Using Lipopolysaccharides
Published on: June 28, 2024
Use of bacteriophage to target bacterial surface structures required for virulence: a systematic search for
1Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA. paul_orndorff@ncsu.edu.
Abstract:
Bacteriophages (phage) that infect pathogenic bacteria often attach to surface receptors that are coincidentally required for virulence. Receptor loss or modification through mutation renders mutants both attenuated and phage resistant. Such attenuated mutants frequently have no apparent laboratory growth defects, but in the host, they fail to exhibit properties needed to produce disease such as mucosal colonization or survival within professional phagocytic cells. The connection between attenuation and phage resistance has been exploited in experimental demonstrations of phage therapy. In such experiments, phage resistant mutants that arise naturally during therapy are inconsequential because of their attenuated status. A more contemporary approach to exploiting this connection involves identifying small effector molecules, identified in high-throughput screens, that inhibit one or more of the steps needed to produce a functioning phage receptor. Since such biosynthetic steps are unique to bacteria, inhibitors can be utilized therapeutically, in lieu of antibiotics. Also, since the inhibitor is specific to a particular bacterium or group of bacteria, no off-target resistance is generated in the host's commensal bacterial population. This brief review covers examples of how mutations that confer phage resistance produce attenuation, and how this coincidental relationship can be exploited in the search for the next generation of therapeutic agents for bacterial diseases.
Insights
Bacterial mutations conferring phage resistance often weaken pathogens, making them less harmful. This link between phage resistance and reduced virulence can guide the development of novel antibacterial therapies.
Area of Science:
- Microbiology
- Bacteriology
- Molecular Biology
Background:
- Bacteriophages (phages) target bacterial surface receptors essential for virulence.
- Mutations conferring phage resistance often result in bacterial attenuation, reducing pathogenicity.
- This dual effect presents opportunities for therapeutic strategies against bacterial infections.
Purpose of the Study:
- To review the relationship between phage resistance and bacterial attenuation.
- To explore the exploitation of this connection for developing novel antibacterial agents.
- To highlight the potential of small molecule inhibitors targeting phage receptor biosynthesis.
Main Methods:
- Review of existing literature on bacteriophage-bacteria interactions.
- Analysis of studies demonstrating attenuation in phage-resistant bacterial mutants.
- Discussion of high-throughput screening for inhibitors of phage receptor production.
Main Results:
- Mutations conferring phage resistance frequently lead to attenuated virulence phenotypes.
- Phage-resistant mutants are often avirulent in vivo despite normal laboratory growth.
- Small molecule inhibitors targeting unique bacterial pathways offer a promising therapeutic avenue.
Conclusions:
- The link between phage resistance and attenuation is a valuable principle for developing new antibacterial treatments.
- Targeting phage receptor biosynthesis with specific inhibitors offers a potential alternative to broad-spectrum antibiotics.
- This approach minimizes resistance development in commensal bacteria and offers specificity against pathogens.
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