Bacterial infections caused by Gram-negative bacteria such as Escherichia coli are frequently resistant to two or more antibiotics (multi-drug resistant). Because introduction of new antibiotics will not eliminate the problem of multi-drug resistance (mdr), mdr type infections constitute a major health threat, especially to patients that acquire such infections nosocomially. The manner by which mdr develops has become an area of intense research and the recent investigations conducted by an international group consisting of American, Portuguese and French scientists have identified the genetic sequence of events that lead to mdr phenotypes of Gram-negative bacteria.
The study, entitled "Antibiotic Stress, Genetic Response and Altered Permeability of E. coli," will be published the 11th April issue of the international, peer-reviewed, open-access online journal of the Public Library of Science, PLoS ONE.
Briefly, prolonged exposure to increasing concentrations of tetracycline cause increased sequential activity of regulatory genes which promote over-expression of genes that code for as many as 9 transporter proteins of distinct efflux pumps which extrude unrelated antibiotics prior to their reaching their intended targets. Parallel to this genetic activity, whereas the level of outer membrane porin proteins Omp F and C decrease with increased antibiotic stress, the level of Omp X continues to increases dramatically. The decrease of Omp C and F appears to result from their being degraded by proteases inasmuch as the activity of genes that code for these proteins are also significantly elevated during prolonged antibiotic stress.
The authors of this study maintain that this is the first time that the response to prolonged exposure to increasing levels of antibiotic cause major changes in the permeability of the bacterium due to over-expression of efflux pumps and down-regulation of porins.