29 September 2007

Are antibiotics doing more harm than good?

Directed Evolution - SOS
Submitted by: 41287925


The efficiency of antibiotics to cure infections has waned over the years as bacteria strains evolve antibiotic resistance. Studies on Staphylococcus aureus have shown that mutations in the gene were self-induced. When the bacterium was under environmental stress (e.g. UV damage and antibiotics), it upregulated genes to repair DNA damage.. This response was coined the SOS response. The SOS response, mainly initiated by derepressing LexA protein via the RecA protein, gives rise to mutations which allows evolution of immunity towards antibiotics. The persistence of bacteria in the host often proves to be fatal.

Another caution of antibiotic usage involves pathogenicity islands on Staphylococcus aureus. Treatment of the bacterium with SOS-response inducing antibiotic, β-lactam, resulted in staphylococcal prophage induction in S. aureus lysogens and replication and high-frequency transfer of pathogeneticity islands. Such antibiotic inadvertently promotes the spread of virulence factors, doing more harm than good in the body.

As bacteria are evolving greater resistance in response to antibiotic therapy, humans have to race ahead in search of newer, more effective drugs, while exercising caution in using SOS response-inducing antibiotics. I wonder, how long more can we stay ahead before the evolution of drug resistance eventually catches up?


References:
1) Elisa M, Carles Ú, Susana C, Noelia S, Íñigo L, Richard P. N, Jordi B, José R. P. (2006)
ß-Lactam Antibiotics Induce the SOS Response and Horizontal Transfer of Virulence Factors in Staphylococcus aureusJ. Bacteriol. 188(7): 2726-2729
http://jb.asm.org/cgi/content/full/188/7/2726?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&volume=188&firstpage=2726&resourcetype=HWCIT


2) Ryan T. C, Marcus B. J,Neill A. G, Timothy D. M, Behnam J,
Scott N. P, Floyd E. R (2007) Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin. Bacteriol. 189(2): 531–539
http://jb.asm.org/cgi/content/full/189/2/531?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&volume=189&firstpage=531&resourcetype=HWCIT


3) Cirz R.T, Chin JK, Andes DR, de Crécy-Lagard V, Craig WA, et al. (2005) Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biol. 3(6): e176
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030176