Use of Specific Phages for the Treatment of Non-Tuberculosis Mycobacterial Infections
Mycobacterial pathogens are the source of a multitude of human diseases. Although usually treatable with antibiotics, poor compliance with a strict antibiotic regimen contributes to the development of drug resistant strains. Some clinically important, non-tuberculous mycobacteria (NTM), such as M. avium and M. abscessus, frequently occur in association with cystic fibrosis (CF). Infection in CF patients come with substantial side effects, including antibiotic-associated deafness and negation of the possibility of lung transplantation, as transplant-associated immunosuppression in infected patients has a high rate of mortality. Clearly, there is an urgent need for new approaches to treating mycobacterial diseases that circumvent drug resistance and other undesirable side effects.
Description
Bacteriophages are viruses that parasitize bacteria, and represent a potential new paradigm in treating drug-resistant mycobacterial diseases. Phages are typically highly specific for a particular bacterial species, and often for individual strains of that species. This specificity is both a blessing and a curse: the high specificity allows efficient targeting and lowers the risk of harmful side effects, but on the other hand, a phage useful in treating one type of bacteria may not be useful for a second patient infected with a different strain. NTM strains have high genetic variability and phages must be selected carefully. Twelve phages, including phage Muddy and its derivatives, have been identified as effective in treating M. abscessus with no detectable resistance, and thus can be used alone or in two-phage cocktails to treat NTM infections with minimal risk of treatment failure due to resistance. Further, researchers have developed a method of using reporter phage derivatives with fluorescent reporter genes to rapidly determine bacterial susceptibility.Applications
· Identification of phages useful for therapy of non-tuberculosis mycobacteria infections· Treatment of highly antibiotic resistant infections
Advantages
· Identification of appropriate phages via reporter phage method is fast, simple, and high-throughput· Minimal resistance leads to high probability of treatment success
· No immunosuppression
· Minimal associated side effects