Extending the lifetime of antibiotics: how can phage therapy help?

• Published in: Future microbiology Vol. 11; no. 9; pp. 1105 - 1107
• Main Authors: Chan, Benjamin K, Brown, Kevin, Kortright, Kaitlyn E, Mao, Stephanie, Turner, Paul E
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.09.2016
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; antimicrobial resistance; Bacteria; Bacteria - drug effects; Bacteria - pathogenicity; Bacteria - virology; Bacterial infections; Drug dosages; Drug resistance; Drug Resistance, Multiple, Bacterial; Evolution; Genotypes; Humans; Medical research; Medicine; Microbial Sensitivity Tests; Multidrug resistance; Mutants; Pathogenicity; Pathogens; Phage Therapy; Phages; Proteins; Salmonella; Strains (organisms); Virulence; World War II; virulence; antimicrobial resistance; phage therapy
• ISSN: 1746-0913; 1746-0921
• DOI: 10.2217/fmb-2016-0133

[...]evolved modifications of surface-expressed receptors may be beneficial to bacteria in the presence of phage, but deleterious in their absence(9). [...]the inevitability of bacterial evolution hints that phage therapy strategies should be devised to capitalize on this possible ‘genetic trade-off’, whereby phage applications exert selection pressure for bacteria to evolve external resistance while suffering worse competitive ability in absence of phage. [...]it intriguingly suggests that widespread use of VTAs could select for less virulent bacterial mutants, causing populations of bacterial pathogens to increasingly harbor genotypes with lower pathogenicity. [...]depending on the underlying ecology (e.g.,waterborne transfer of fecal-oral transmitted bacteria), a VTA could actually facilitate the spread of less virulent bacterial genotypes in natural environments. The mutational spectra governing P. aeruginosa resistance to phage OMKO1 are the subject of ongoing studies, but consistent observations of the trade-off across environmental, clinical and lab strains of P. aeruginosa strongly suggest that phage OMKO1 is a promising VTA candidate. [...]it was observed that phage selection caused multidrug-resistant bacterial strains to become sensitive to many antibiotics at clinically relevant levels, indicating that these previously inefficacious drugs should be effective at combating the bacteria if administered in combination with phage OMKO1. Because this strategy would necessarily allow reduced doses of traditional antibiotics to be administered, it should additionally weaken the current selection pressure exerted by these same antibiotics.