AUTHOR=Kepplinger Bernhard , Wen Xin , Tyler Andrew Robert , Kim Byung-Yong , Brown James , Banks Peter , Dashti Yousef , Mackenzie Eilidh Sohini , Wills Corinne , Kawai Yoshikazu , Waldron Kevin John , Allenby Nicholas Edward Ellis , Wu Ling Juan , Hall Michael John , Errington Jeff TITLE=Mirubactin C rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis JOURNAL=Frontiers in Microbiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1004737 DOI=10.3389/fmicb.2022.1004737 ISSN=1664-302X ABSTRACT=

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a protein machine called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening > 2,000 extracts from a diverse collection of actinobacteria, we identified a compound, mirubactin C, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed using synthetic mirubactin C. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin C rescuing activity is not due simply to iron sequestration. The results support an emerging view that the functions of bacterial siderophores extend well beyond simply iron binding and uptake.