Auditorium

In all domains of life, nucleotide-based second messengers allow a rapid integration of external and internal signals into fine-tuned regulatory pathways that control cellular responses to changing conditions. The cyclic dinucleotide c-di-GMP is one of the most important signalling molecules in microbiology. Its role has been studied extensively in unicellular Gram-negative bacteria, where c-di-GMP levels control the lifestyle switch between biofilm formation and planktonic swimming (“stick or swim”). However, much less is known about the role of c-di-GMP in Gram-positives like Streptomyces. Streptomyces are filamentous bacteria with a fascinating developmental life cycle involving progression from vegetative growth to the production of reproductive aerial hyphae, which differentiate into long chains of exospores. The regulation of development was already our major focus when, in 2013, my postdoc Natalia Tschowri, now a Professor in Hannover, did a simple experiment that profoundly changed our view of what we were working on. Natalia engineered high and low levels of c-di-GMP in Streptomyces venezuelae and found that this nucleotide somehow controls progression through the life cycle. From then on, discovering how c-di-GMP acts in Streptomyces development became the key question in the lab. I will describe how we went on to discover, at the molecular and mechanistic level, the ways in which c-di-GMP controls the two most dramatic developmental transitions in the Streptomyces life cycle: the formation of the aerial hyphae, and the differentiation of these reproductive structures into spores.