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Seven small proteins tie a bacterial signal to spore-making

Clostridioides difficile makes spores that let it persist and spread, and high levels of the signal c-di-GMP hold that process down. A Nature Communications paper finds a family of small membrane proteins whose genes are switched by c-di-GMP riboswitches. Raising one of them, CD1980.2, turned sporulation genes on and increased spores. Deleting all 7 genes left a severe sporulation defect, and adding still more c-di-GMP in that mutant did not push spores down any further. The work is one bacterial study.

Science··Midday
A blue-gloved hand lifts a covered culture plate above an open glass culture jar holding stacked plates on a laboratory bench.

A riboswitch family sits on the spore pathway

Clostridioides difficile uses spores to persist and to spread. High c-di-GMP, a small signalling molecule, inhibits sporulation, and the route of that inhibition had been unclear. The paper identifies a conserved family of small proteins that sit in the membrane. Their genes carry c-di-GMP riboswitches.[1]

Transcriptome measurements showed that c-di-GMP quiets these genes. Reporter tests put the control at the riboswitch, through premature termination of the message. The signal and the spore pathway meet at this gene family.[1]

One gene raised spores; losing all seven cut them

Overexpressing a single member, CD1980.2, was enough to switch on sporulation genes, including sigma factors and the genes they govern, and to raise spore formation. The proteins are described as overlapping in role rather than each doing a private job.[1]

Spore-making efficiency dropped as more genes from the family were removed. The strain missing all 7 had a severe sporulation defect. That graded loss is the evidence the authors use for a shared, cumulative role.[1]

Extra signal did nothing once the family was gone

In the mutant that lacked all 7 genes, raising c-di-GMP further did not reduce sporulation any more. The authors read that as a model in which the signal inhibits spores by keeping this protein family quiet. Spores are how C. difficile persists and spreads, and the map is from this one bacterium, not a survey of other spore-formers.[1]

References

  1. News sourceNature CommunicationsSmall proteins connect a c-di-GMP signal to C. difficile spores↩1↩2↩3↩4↩5