A Novel and Efficient Platform for Discovering Noncanonical Quorum-Quenching Proteins

Liao, Jinxing; Xiong, Dan; Shen, Danyu; Wang, Lu; Shao, Xiaolong; Li, Tao; Qian, Guoliang

doi:10.1128/spectrum.03437-22

Cited by 2 publications

(1 citation statement)

References 55 publications

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“…The genus not only secretes a large amount of extracellular hydrolases (α- proteolytic enzyme, β-1,3-glucanase, chitinase, etc.) but also produces many bioactive natural products (NPs) ( 2 – 4 ). Polycyclic tetramate macrolactams have been the most extensively studied NPs, particularly the heat-stable antifungal factor (HSAF) from Lysobacter enzymogenes strains OH11 and C3, which shows a broad-spectrum antifungal activity with a distinct mode of action ( 5 – 7 ) .…”

Section: Introductionmentioning

confidence: 99%

Iron ions regulate antifungal HSAF biosynthesis in Lysobacter enzymogenes by manipulating the DNA-binding affinity of the ferric uptake regulator (Fur)

Tang,

Wang,

et al. 2023

Microbiol Spectr

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Heat-stable antifungal factor (HSAF), produced by Lysobacter enzymogenes OH11, is regarded as a potential biological pesticide due to its broad-spectrum antifungal activity and novel mode of action. However, the current production of HSAF is low and cannot meet the requirements for large-scale production. Herein, we discovered that iron ions greatly promoted HSAF production, and the ferric uptake regulator (Fur) was involved in this regulatory process. Fur was also found to participate in the regulation of iron homeostasis in OH11 via the classic inhibition mechanism of Holo -Fur. Furthermore, Fur was collectively observed to directly bind to the promoter of the HSAF biosynthesis gene, and its DNA-binding affinity was attenuated by the addition of iron ions in vitro and in vivo . Its regulatory mechanism followed the uncommon inhibition mechanism of Apo -Fur. In summary, Fur exhibited a bidirectional regulatory mechanism in OH11. This study reveals a novel regulatory mechanism whereby Fur upregulates the biosynthesis of secondary metabolites. These findings contribute to the improvement of HSAF production and may guide its development into biological pesticides. IMPORTANCE HSAF possesses potent and broad antifungal activity with a novel mode of action. The HSAF yield is critical for fermentation production. In this study, iron ions were found to increase HSAF production, and the specific mechanism was elaborated. These results provide theoretical support for genetic transformation to improve HSAF yield, supporting its development into biological pesticides.

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Section: Introductionmentioning

confidence: 99%

Iron ions regulate antifungal HSAF biosynthesis in Lysobacter enzymogenes by manipulating the DNA-binding affinity of the ferric uptake regulator (Fur)

Tang,

Wang,

et al. 2023

Microbiol Spectr

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Quorum quenching by a type IVA secretion system effector

et al. 2023

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Proteobacteria primarily utilize acyl-homoserine lactones (AHLs) as quorum-sensing signals for intra-/interspecies communication to control pathogen infections. Enzymatic degradation of AHL represents the major quorum-quenching mechanism that has been developed as a promising approach to prevent bacterial infections. Here we identified a novel quorum-quenching mechanism revealed by an effector of the type IVA secretion system (T4ASS) in bacterial interspecies competition. We found that the soil antifungal bacterium Lysobacter enzymogenes OH11 (OH11) could use T4ASS to deliver the effector protein Le1288 into the cytoplasm of another soil microbiome bacterium Pseudomonas fluorescens 2P24 (2P24). Le1288 did not degrade AHL, whereas its delivery to strain 2P24 significantly impaired AHL production through binding to the AHL synthase PcoI. Therefore, we defined Le1288 as LqqE1 (Lysobacterquorum-quenching effector 1). Formation of the LqqE1-PcoI complex enabled LqqE1 to block the ability of PcoI to recognize/bind S-adenosy-L-methionine, a substrate required for AHL synthesis. This LqqE1-triggered interspecies quorum-quenching in bacteria seemed to be of key ecological significance, as it conferred strain OH11 a better competitive advantage in killing strain 2P24 via cell-to-cell contact. This novel quorum-quenching also appeared to be adopted by other T4ASS-production bacteria. Our findings suggest a novel quorum-quenching that occurred naturally in bacterial interspecies interactions within the soil microbiome by effector translocation. Finally, we presented two case studies showing the application potential of LqqE1 to block AHL signaling in the human pathogen Pseudomonas aeruginosa and the plant pathogen Ralstonia solanacearum.

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A Novel and Efficient Platform for Discovering Noncanonical Quorum-Quenching Proteins

Abstract: Targeting and blocking bacterial quorum sensing (QS), the process known as quorum quenching (QQ) is an effective mean to control bacterial infection and overcome the emerging antibiotic resistance. Previously, diverse QS signal-degradation enzymes are identified as canonical QQ proteins.

Cited by 2 publications

References 55 publications

Iron ions regulate antifungal HSAF biosynthesis in Lysobacter enzymogenes by manipulating the DNA-binding affinity of the ferric uptake regulator (Fur)

Iron ions regulate antifungal HSAF biosynthesis in Lysobacter enzymogenes by manipulating the DNA-binding affinity of the ferric uptake regulator (Fur)

Quorum quenching by a type IVA secretion system effector

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