All roads lead to Rome: Cyclic di-GMP differentially regulates extracellular electron transfer in <i>Geobacter</i> biofilms

<p>Microbial extracellular electron transfer (EET) in dissimilatory metal-reducing microorganisms (DMRMs) is a widespread biological process and is involved in biogeochemical cycling of a variety of elements on the planet of Earth. However, the regulatory networks controlling such important process have been under-investigated. Here, we reported that the intracellular messenger bis-(3��-5��) cyclic dimeric guanosine monophosphate (c-di-GMP) signaling network controls EET in <i>Geobacter sulfurreducens</i>. The low and high levels of c-di-GMP both improved EET in <i>G. sulfurreducens</i> electrode-respiring biofilms by differentially regulating the expression of EET-associated genes. In particular, we found that a low c-di-GMP level reduced the formation of the anode biofilm but enhanced EET by upregulating the transcription of all known nanowire genes (i.e., <i>pilA</i>, <i>omcS</i>, <i>omcZ</i> and <i>omcE</i>). Upregulated <i>omcZ</i> transcription was further determined to play a decisive role in improving EET. Given that c-di-GMP is present in diverse DMRMs, this study substantially expands our understanding of the regulatory role of c-di-GMP signaling and the varied strategies for efficient EET employed by DMRMs. In addition to be fundamentally significant to understand microbe-mineral and microbe-microbe interactions driven by EET, it is also instructive to develop effective engineered microbial systems for practical applications.</p>