
細菌バイオフィルムにおいて、細胞接着の過程で上昇する環状ジグアノシン一リン酸(c-di-GMP)が、毒素タンパク質HipHの発現と活性を制御することで、遺伝体の安定性と抗生物質耐性を決定する。


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Biofilms are complex bacterial communities characterized by a high persister prevalence, which contributes to chronic and relapsing infections. Historically, biofilm persister formation has been linked to constraints imposed by their dense structures. However, we observed an elevated persister frequency accompanying the stage of cell adhesion, marking the onset of biofilm development. Subsequent mechanistic studies uncovered a distinctive type of toxin-antitoxin (TA) module triggered by cell adhesion, which is responsible for this elevation. In this module, the toxin HipH acts as a genotoxic deoxyribonuclease, inducing DNA double strand breaks and genome instability. While the second messenger c-di-GMP functions as the antitoxin, exerting control over HipH expression and activity. The dynamic interplay between c-di-GMP and HipH levels emerges as a crucial determinant governing genome stability and persister generation within biofilms. These findings unveil a unique TA system, where small molecules act as the antitoxin, outlining a biofilm-specific molecular mechanism influencing genome stability and antibiotic persistence, with potential implications for treating biofilm infections.

### Competing Interest Statement

The authors have declared no competing interest.

Cyclic di-GMP as an Antitoxin Regulates Bacterial Genome Stability and Antibiotic Persistence in Biofilms

細菌バイオフィルムにおける抗毒素としての環状ジグアノシン一リン酸-c-di-gmp-が遺伝体の安定性と抗生物質耐性に与える影響


細菌バイオフィルムにおける抗毒素としての環状ジグアノシン一リン酸(c-di-GMP)が遺伝体の安定性と抗生物質耐性に与える影響
