Chapter 16, Problem 6CHI

Studies of phage therapy to treat bacterial infections were largely abandoned in the United States when antibiotics were discovered. However, the increasing number of important bacterial pathogens resistant to antibiotics has reinvigorated research in this area. One approach being examined is the use of phage to deliver genes that reverse an antibiotic-resistant phenotype. This is then coupled with treatment using the antibiotic to which the bacterium is once again susceptible. To determine if this was feasible, scientists transduced streptomycin-resistant E. coli cells with one of two different temperate phages. One phage (φ1) carried a wild-type rpsL gene; this gene encodes one of the proteins found in the 30S ribosomal subunit, the target of streptomycin (see section 9.4). The second phage (φ2) carried two rpsL genes: the wild-type gene and one containing numerous silent mutations. Both lysogenized bacteria were tested for their sensitivity to streptomycin by determining the minimum inhibitory concentration (MIC; see section 9.3) and comparing these MIC values to that of the parent resistant strain. E. coli cells lysogenized with φ1 had an MIC one-tenth that of the resistant strain. Those bacteria lysogenized with φ2 had an MIC level nearly identical to that of streptomycin-sensitive E. coli strains. Suggest why scientists used this approach rather than simply using a virulent strain to kill streptomycin-resistant strains. Why do you think scientists included the rpsL gene having many silent mutations? Would this approach work with penicillin-resistant bacteria? Explain your answer.

Read the original paper: Edgar, R., et al. 2012. Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Appl. Environ. Microbiol. 78(3):744.