New antibiotics are constantly being devised to overcome a major problem in today’s society, that is drug resistance. In response, bacteria are continually evolving new ways around these antibiotics, resulting in ineffectiveness of treatment. DNA damage is caused by many factors including antibiotics, DNA polymerases, and UV radiation, which activate the SOS response, an inducible, DNA repair system.
The SOS response uses the RecA inducer protein stimulated by single-stranded DNA that is caused by damage, to inactivate the LexA repressor protein, inducing the response. Presence of the LexA protein represses the SOS response, inhibiting or limiting DNA repair, and resulting in resistance to the antibiotic.
The SOS response has played a significant role in the bacterial world, inducing mutations and genetic exchanges. Recent studies have shown that the SOS pathway may be vital in the acquisition of bacterial mutations, which lead to antibiotic resistance.
Staphylococcus aureus, a gram-positive pathogen, is unique in its ability to easily acquire multidrug resistance, and its incredible ability to persist and adapt. To determine how this pathogen persists when exposed to antibiotics, a study by Cirz et al, in 2007 observed its response to the antibiotic ciprofloxacin. When the DNA is damaged by ciprofloxacin, RecA binds to the damaged, single-stranded DNA as well as the repressor gene LexA. This cleavage inactivates the LexA gene, resulting in induction of the SOS genes. Therefore, this shows that the SOS response actually facilitates survival and evolution of resistance, by inducing mutation.
Primary reference:
Cirz, R.T., Chin, J.K., Andes, D.R., Crecy-Lagard, V., Craig, W.A., Romesberg, F,E. (2005). Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biology 3(6): 1024-1033.
Secondary references:
Cirz, R.T., Jones, M.B., Gingles, N.A., Minogue, T.D., Jarrahi, B. Peterson, S.N., Romesberg, F.E. (2007). Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin. Journal Of Bacteriology 189(2): 531-539.
McKenzie, G.J., Harris, R. S., Lee, P.L., Rosenberg, S.M. (2000). The SOS response regulates adaptive mutation. PNAS 97(12): 6646-6651.
Michel, B. (2005). After 30 Years of Study, the bacterial SOS Response Still Surprises Us. PloS Biology 3(7): e255 doi:10.1371/journal.pbio.0030255
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