Local c- di- GMP signaling, triggered by cross- regulation of cAMP- CRP and c- di- GMP, controls biofilm formation under nutrient limitation

• 成果类型: Article
• 署名作者: Sun, Di; Liu, Xiaobo; Zhang, Ying; Shi, Rui; Ru, Yunrui; Zhou, Xuge; Chen, Ying; Yang, Jing; Liu, Jiawen; Zhu, Jingrong; Liu, Cong; Liu, Weijie
• 署名单位: Jiangsu Normal University; Nanjing University of Science & Technology; Beijing Institute of Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15222
• DOI: 10.1073/pnas.2516964122
• 发表日期: 2025-09-02
• 关键词: protein

摘要

Bacteria have several nucleotide second messengers, most of which act as global regulators to control a wide range of bacterial physiological processes. Studies usually focus on a single second messenger, and the mechanisms and physiological significance of the cross-regulation between different nucleotide second messengers are often unclear. Here, we show that Shewanella putrefaciens can form biofilms in both nutrient-rich and nutrient-poor media. While both are controlled by c-di-GMP, the regulatory models differ. Under low nutrient conditions, cross-regulation of cAMP-CRP and c-di-GMP occurs at the transcriptional and posttranslational levels, thereby controlling biofilm development. During the early stages of biofilm development, cAMP-CRP directly promotes the transcription of a PDE gene, lrbR, by LrbA. Additionally, cAMP-CRP recruits LrbR to BpfD to suppress early biofilm formation via LrbR-dependent local degradation of c-di-GMP. Finally, as intracellular LrbR levels decrease, cAMP-CRP-BpfD enables a rapid shift to biofilm development and supports biofilm maintenance. Under high nutrient conditions, this cross-regulation does not occur, resulting in a positive correlation between global c-di-GMP levels and biofilm biomass. The identification of distinct modes of biofilm regulation in different nutrients will provide a theoretical basis for future targeted control of biofilm formation in different nutrient environments. Significance Decades of research have established cAMP-CRP as a global transcription factor in bacteria. Here, we demonstrate that cross-regulation between cAMP-CRP and c-di-GMP occurs at both the transcriptional and posttranslational levels. Not only does cAMP-CRP regulate the transcription of lrbR, which encodes a phosphodiesterase (PDE), but it also interacts directly with LrbR and the c-di-GMP effector BpfD. This cross-regulation means that a moderate increase in intracellular c-di-GMP levels leads to a rapid increase in biofilm biomass, but only in a nutrient-limited environment. Since the proteins involved in this cross-regulation are conserved in many bacteria, this cross-regulation may be common to a wide range of bacteria in response to nutrient conditions.