Uncleavable Lex A – E. coli’s Kryptonite

Earlier this year American scientists discovered that the repressor protein Lex A, involved in SOS regulation of enteropathogenic Escherichia coli, also plays a part in mediating the Type III secretion system responsible for causing watery diarrhoea.[1]

This Type III secretion system is responsible for causing attaching and effacing intestinal lesions, which in turn lead to watery diarrhoea. The disease in found primarily in developing countries and can have drastic effects due to water and electrolyte loss in already malnutritioned children.

Jay Mellies and his colleagues discovered that enteropathogenic Escherichia coli that contained a mutation encoding for an uncleavable Lex A protein showed reduced secretions and thus reduced pathogenicity.

In 2005 the same protein was found to be responsible for inducing mutations during SOS response in E. coli following specific antibiotic pressures.[2] It was found that mutant E. coli strains containing an uncleavable Lex A protein were unable to induce mutations and thus unable to acquire antibiotic resistance. This means that by rendering E. coli unable to cleave Lex A they have decreased virulence factors and a malfunction in producing mutations that may allow them to become resistant to antibiotics. It is like exposing Superman to Kryptonite,[3] we can make them weak and unable to use their superpowers.

References:

1 Mellies, J.L. et al. (2007) SOS Regulation of the Type III Secretion System of Enteropathogenic Escherichia coli, Journal of Bacteriology, April, p. 2863-2872

2 Cirz, R.T. et al. (2005) Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biology 3, e176

3 http://site.supermanthrutheages.com/Encyclopaedia/kryptonite.php (accessed on 9/10/07)

This blog was written by Ivana Ferreira 41214631

SOS response the call for variation?

The adaptive abilities of bacteria to survive antibiotic treatments have long been noted in the scientific community. More importantly the prevalence of this rapid acquirement of antibiotic resistance is such that it occurs not so much by chance, but by an adaptive mechanism, but how does this happen?

The SOS response is a transcriptional response to environmental stress causing changes in the regulation of numerous genes leading to mutations in the genome. These mutations are suspected to be the possible origin of the adaptive mutations involved in antibiotic resistance.

A recent paper by Cirz, Ryan T. et. al used DNA micro arrays to study the genetic effects of the SOS response in Pseudomonas aeruginosa in the presence of the antibiotic Ciprofloxacin and the possible effects of inhibition of LexA cleavage on antibiotic resistance. P.aeruginosa infections are well known for being hard to eradicate when using antibiotic therapy due to evolution of antibiotic resistance. The results of the paper indicate that the SOS response during antibiotic treatments allows the organism to gain mutations with the potential of obtaining resistance. Although the SOS response in P.aeruginosa is not exactly the same as in other bacteria such as Escherichia coli it has the still allows the organism time to adapt.

References

Cirz, R. T., O'Neill, B. M., Hammond, J. A., Head, S. R., Romesberg, F. E. (2006). Defining the Pseudomonas aeruginosa SOS Response and Its Role in the Global Response to the Antibiotic Ciprofloxacin. Journal of Bacteriology, 188, 7101-7110

Cirz, R. T., Chin, J. K., Andes, D. R., de Crecy-Lagard, V., Craig, W. A., Romesberg, F. E. (2005). Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance. PLoS Biology, 3, 1024-1033

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