Abstract
Bacteria in nature often reside in differentiated communities termed biofilms, which are an active interphase between uni-cellular and multicellular life states for bacteria. Here we demonstrate that the development of B. subtilis biofilms is dependent on the use of glutamine or glutamate as a nitrogen source. We show a differential metabolic requirement within the biofilm; while glutamine is necessary for the dividing cells at the edges, the inner cell mass utilizes lactic acid. Our results indicate that biofilm cells preserve a short-term memory of glutamate metabolism. Finally, we establish that drugs that target glutamine and glutamate utilization restrict biofilm development. Overall, our work reveals a spatial regulation of nitrogen and carbon metabolism within the biofilm, which contributes to the fitness of bacterial complex communities. This acquired metabolic division of labor within biofilm can serve as a target for novel anti-biofilm chemotherapies
Highlights
Despite the widely held view of bacteria as unicellular organisms that struggle for individual survival, in nature, bacteria establish complex communities, referred to as biofilms
We first evaluated the necessity of both glutamine and glutamate for bacterial biofilm development by measuring biofilm maturation, biomass and planktonic growth, following supplementation of different nitrogen sources to the biofilm defined media
In the traditional biofilm defined medium which contains glutamate or glutamine as the primary nitrogen source, we found that B. subtilis wild type strains form an almost perfect circular biofilm shape, characterized by thick branching wrinkles that surround a defined circular center with smaller, more delicate, and denser creases (Fig. 1A upper panel)
Summary
Despite the widely held view of bacteria as unicellular organisms that struggle for individual survival, in nature, bacteria establish complex communities, referred to as biofilms. Derived from a single genetically identical clone, bacteria within mono-species biofilms are heterogeneous in terms of metabolism, gene expression and physiology, creating diverse biological niches within the biofilm[7,38] This heterogeneity facilitates response to changing environmental conditions, allowing survival and growth of the biofilm community[39,40]. Glutamate dehydrogenase paralogous GudB and RocG which catalyze glutamate, contribute to the fitness of biofilm cells and interference with their transcriptional regulation has deleterious effects[44] While both glutamine and glutamate were shown to be important to biofilm fitness, their specific contribution to biofilm development remains to be determined. It is still unknown whether they provide mainly carbon, nitrogen, or both. We systematically explore the metabolic contributions of glutamate and glutamine to biofilm development for translational and therapeutic applications
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