@article {DinStaBer2011, title = {{Co-evolution of ABC-transporters and two-component regulatory systems as resistance modules against antimicrobial peptides in Firmicutes bacteria}}, journal = {Journal of Bacteriology}, volume = {193}, number = {15}, year = {2011}, note = {(accepted)}, month = {August}, pages = {3851--3862}, abstract = {In Firmicutes bacteria, ABC-transporters have been recognized as important resistance determinants against antimicrobial peptides. Together with neighboring two-component systems (TCSs), which regulate their expression, they form specific detoxification modules. Both the transport permease and sensor kinase components show unusual domain architecture: the permeases contain large extracellular domain, while the sensor kinases lack any obvious input domain. One of the best characterized examples is the bacitracin-resistance module BceRS-BceAB of Bacillus subtilis. Strikingly, in this system the ABC-transporter and TCS have an absolute mutual requirement for each other in both sensing of and resistance to bacitracin, suggesting a novel mode of signal transduction in which the transporter constitutes the actual sensor. We identified over 250 such BceAB-like ABC-transporters in the current databases. They occured almost exclusively in Firmicutes bacteria, and 80\% were associated with a BceRS-like TCS. Phylogenetic analyses of the permease and sensor kinase components revealed a tight evolutionary correlation. Our findings suggest a direct regulatory interaction between the ABC-transporters and TCSs, mediating communication between both components. Based on their observed co-clustering and conservation of response regulator binding sites, we could identify putative corresponding two-component systems for transporters lacking a regulatory system in their immediate neighborhood. Taken together, our results show that these types of ABC-transporters and TCSs have co-evolved to form self-sufficient detoxification modules against antimicrobial peptides, widely distributed among Firmicutes bacteria.}, doi = {10.1128/JB.05175-11}, author = {Dintner Sebastian and Anna Staro{\'n} and Evi Berchtold and Tobias Petri and Thorsten Mascher and Susanne Gebhard} }