Antibiotic resistance has long been the bane of the medical profession. As strains of bacteria become exposed to various antibiotics some are able to survive due to random genetic variability in the population. These members of the population have a mutation in their genome that confers antibiotic resistance, allowing them to reproduce and spread until a new resistant strain of organism emerges. A recent study by Cirz et al. (2005) (as cited in Gene, M. 2005) showed that bacteria actively induce these mutations to increase variability when under stress through a process known as the SOS response.
However the answer to this problem may already exist. In 1999, a paper by Felczak et al. showed that there was a mutation in E. coli which inhibited SOS induced mutagenesis. Scientists tested the antimutagenic effects of the isfA mutation on a variety of mutator strains in the Lac Z gene. An analysis revealed that the isfA mutation inhibited UV induced transitions and transversions (known to use the SOS pathway) but had no effect on mutagens that did not involve the SOS pathway(Felczak et al., 1999). The isfA mutations acts to inhibit the processing of UmuD to UmuD'; an essential process in SOS mutagenesis resulting from Lex A cleavage.
In closing, SOS mediated directed evolution in bacteria is a problem with no current solution other than the introduction of new antibiotics. However, this is just a stall at best. The isfA mutation may be able to increase the lifespan of many antibiotics by disabling the very mechanism by which bacteria become resistant. Further research is required before this mutation can be applied to medical fields, however it has lots of potential.
Tom Reddel
41202656
Primary reference
Felczak, M., Bebenek, A., Pietrzykowska, I. (1999), The isfA mutation specifically inhibits SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution. Mutagenesis. 3(14), pp 295-300
http://mutage.oxfordjournals.org/cgi/content/full/14/3/295#T2
Secondary references
Cirz, R., Chin, J., Andes, D., Crecy-Lagard, V., Craig, W., Romesberg, F. (2005), Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol 3(6) pp 176-186
biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030176&ct=1
Gene M, (2005), Evolution Under Intrinsic Control
http://www.idthink.net/biot/lexA/index.html
