under construction
Bacterial efflux pumps
There are essentially three ways to deal with harmful substances. The most common is to destroy toxic molecules by breaking them down. An example can be the usage of beta-lactamases, a class of enzymes that break open the β-lactam rings of penicillins, which then become inactive. Alternatively, an organism can evolve resistance by modifying the target of the toxin. When a given antibiotic binds to a particular place in an enzyme, new mutants with modified binding sites can appear, lowering the toxicity of the antibiotic.
The third way is to actively remove the harmful substance from the space where it can cause harm. Bacteria achieve this feat by using efflux pumps, protein complexes that expel toxins from inside the cell to the environment. Among several families of efflux pumps, our interest lands on the Resistance-Nodulation-Division family, RND. These large protein complexes connect the inner and outer membranes of the bacterial cell, providing an exit path for toxins, antibiotics, superfluous metabolites, and metal ions.
The interesting thing is that most bacteria apparently posses more RND efflux pumps than they need. For instance, the most commonly studied bacterium Escherichia coli, contains five efflux pump systems, with virtually overlapping functions. Deletion of any of the five systems does not seem to have any effect, and only when all five systems are deleted simultaneously, such bacteria suffer from the lack of the efflux.
(An exception to this is the existence of RND efflux pumps that specifically export metal ions, for instance the CusCFBA system of E. coli.)
In this project, we set out to investigate the evolutionary origins of one of the efflux pumps, namely the MdtABC system. Mdt stands for multidrug transport, a rather generic name given to reflect a broad range of substances that can be transported by this protein assembly. While the vast majority of the RND efflux pumps are composed of one inner membrane component, the MdtABC system contains two, MdtB and C. Why?
In our article, Phylogenetic analysis reveals an ancient gene duplication as the origin of the MdtABC efflux pump, we deducted the evolutionary history of this assembly. We showed that, contrary to the common belief, the inner membrane component was duplicated only once, early in the evolution of bacteria, and the overall architecture of the complex was kept relatively stable throughout the billions of years. This finding suggests that the MdtABC system has a specific and unique role in the bacterial metabolism, and it cannot be effectively replaced by the other efflux pumps. Otherwise, the MdtABC would have already been lost as redundant.
What role does the MdtABC system play? It remains to be uncovered.
