Nucleotide second messengers in bacterial decision making

Thompson, Catriona M A; Malone, Jacob

doi:10.1016/j.mib.2020.02.006

Cited by 14 publications

(16 citation statements)

References 47 publications

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“…Although transcriptional regulation is important for bacterial survival and adaptation, bacteria also rely on translational regulation to respond to changes in their environment (5). Bacteria are able to exert this control by deploying second messenger signals (6), directly altering the ribosome (7) or impacting mRNA stability and accessibility via pathways such as Gac-Rsm (8, 9). It is currently unknown whether conjugative plasmids are able to manipulate translational regulatory pathways.…”

Section: Introductionmentioning

confidence: 99%

Plasmid manipulation of bacterial behaviour through translational regulatory crosstalk

Thompson

Hall

Chandra

et al. 2022

Preprint

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Beyond their role in horizontal gene transfer, conjugative plasmids commonly encode homologues of bacterial regulators. Known plasmid regulator homologues have highly targeted effects upon the transcription of specific bacterial traits. Here, we characterise a plasmid translational regulator, RsmQ, capable of taking global regulatory control in Pseudomonas fluorescens and causing a behavioural switch from motile to sessile lifestyle. RsmQ acts as a global regulator controlling the host proteome through direct interaction with host mRNAs and interference with the host's translational regulatory network. This mRNA interference leads to largescale proteomic changes in metabolic genes, key regulators and genes involved in chemotaxis, thus controlling bacterial metabolism and motility. Moreover, comparative analyses found RsmQ on a large number of divergent plasmids isolated from multiple bacterial host taxa, suggesting the widespread importance of RsmQ for manipulating bacterial behaviour across clinical, environmental, and agricultural niches. RsmQ is a widespread plasmid global translational regulator primarily evolved for host chromosomal control to manipulate bacterial behaviour and lifestyle.

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Section: Introductionmentioning

confidence: 99%

Plasmid manipulation of bacterial behaviour through translational regulatory crosstalk

Thompson

Hall

Chandra

et al. 2022

Preprint

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“…c-di-GMP has emerged as a universal second messenger that is widely distributed within the bacterial kingdom ( 20 – 22 ). c-di-GMP has been shown to regulate cell motility, biofilm formation, the production of virulence factors, cell differentiation, the cell cycle, and other cellular processes in a wide range of species ( 22 – 24 ). Cellular c-di-GMP levels are modulated by diguanylate cyclases (DGCs), which are characterized by GGDEF domains and are involved in its synthesis, and phosphodiesterases (PDEs), which harbor either EAL or HD-GYP catalytic domains that catalyze c-di-GMP degradation ( 25 – 27 ).…”

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of c-di-GMP Signaling Mechanisms and Biological Functions in Dickeya zeae EC1

Chen

Zhou

et al. 2020

mBio

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Dickeya zeae is an important and aggressive bacterial phytopathogen that can cause substantial economic losses in banana and rice plantations. We previously showed that c-di-GMP signaling proteins (cyclases/phosphodiesterases) in D. zeae strain EC1 play a significant role in the bacterial sessile-to-motile transition. To determine whether there is any synergistic effect among these c-di-GMP signaling proteins, we prepared a series of mutant strains by generating consecutive in-frame deletions of the genes encoding diguanylate cyclases (which make c-di-GMP) and phosphodiesterases (which break down c-di-GMP), respectively, using EC1 as a parental strain. The results showed that the complete deletion of all the putative diguanylate cyclases resulted in significantly increased bacterial motility and abrogated biofilm formation but did not appear to affect pathogenicity and virulence factor production. In contrast, the deletion of all the c-di-GMP phosphodiesterase genes disabled motility and prevented the invasion of EC1 into rice seeds. By measuring the c-di-GMP concentrations and swimming motility of all the mutants, we propose that c-di-GMP controlled swimming behavior through a multitiered program in a c-di-GMP concentration-dependent manner, which could be described as an L-shaped regression curve. These features are quite different from those that have been shown for other bacterial species such as Salmonella and Caulobacter crescentus. Further analysis identified three c-di-GMP signaling proteins, i.e., PDE10355, DGC14945, and PDE14950, that play dominant roles in influencing the global c-di-GMP pool of strain EC1. The findings from this study highlight the complexity and plasticity of c-di-GMP regulatory circuits in different bacterial species. IMPORTANCE Dickeya zeae is the etiological agent of bacterial foot rot disease, which can cause massive economic losses in banana and rice plantations. Genome sequence analysis showed that D. zeae strain EC1 contains multiple c-di-GMP turnover genes, but their roles and regulatory mechanisms in bacterial physiology and virulence remain vague. By generating consecutive in-frame deletion mutants of the genes encoding c-di-GMP biosynthesis and degradation, respectively, we analyzed the individual and collective impacts of these c-di-GMP metabolic genes on the c-di-GMP global pool, bacterial physiology, and virulence. The significance of our study is in identifying the mechanism of c-di-GMP signaling in strain EC1 more clearly, which expands the c-di-GMP regulating patterns in Gram-negative species. The methods and experimental designs in this research will provide a valuable reference for the exploration of the complex c-di-GMP regulation mechanisms in other bacteria.

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“…The second messenger cyclic di-guanosine monophosphate (c-di-GMP) has emerged as a signaling molecule in Gram-positive and Gram-negative bacteria governing the process of biofilm formation, biosynthesis of EPS, virulence and suppression of cell motility. The enzyme diguanylate cyclase is essential for synthesis of c-di-GMP, inhibition of which has proven to terminate biofilm formation, alluding to the significance of c-di-GMP in the bacterial signaling process [128][129][130][131][132][133][134][135].…”

Section: Nucleotide Second Messenger Signaling Modulating Moleculesmentioning

confidence: 99%

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

et al. 2022

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A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for identifying a myriad of antibiofilm agents and their mechanism of biofilm inhibition, including extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, and cyclic diguanylate inhibitors. Furthermore, we present the structure–activity relationships (SAR) of these agents, including recently discovered biofilm inhibitors, nature-derived bioactive scaffolds, synthetic small molecules, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids and antibiotics. We hope to fuel interest and focus research efforts on the development of agents targeting the uniquely complex, physical and chemical heterogeneous biofilms through a multipronged approach and combinatorial therapeutics for a more effective control and management of biofilms across diseases.

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Nucleotide second messengers in bacterial decision making

Cited by 14 publications

References 47 publications

Plasmid manipulation of bacterial behaviour through translational regulatory crosstalk

Plasmid manipulation of bacterial behaviour through translational regulatory crosstalk

Systematic Analysis of c-di-GMP Signaling Mechanisms and Biological Functions in Dickeya zeae EC1

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

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