Inhibition of biofilm in Bacillus amyloliquefaciens Q-426 by diketopiperazines

Wang, Jianhua; Yang, Cuiyun; Fang, Shu; Lü, Jian; Quan, Chunshan

doi:10.1007/s11274-016-2106-4

Cited by 13 publications

(17 citation statements)

References 55 publications

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“…With so many structural combinations possible, there are many more examples of DKPs that influence microbial QS systems, some in biofilm formation, and some even in Vibrio spp. (43)(44)(45)(46). For example, cyclo(L-Phe-L-Pro), which was originally isolated from V. vulnificus, was shown to activate the V. fischeri luminescence locus (47).…”

Section: Resultsmentioning

confidence: 99%

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A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ

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Ludvik

Lazzara

et al. 2021

mBio

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The lifelong relationship between the Hawaiian bobtail squid Euprymna scolopes and its microbial symbiont Vibrio fischeri represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the host in a process termed counterillumination. The squid host hatches without its symbionts, which must be acquired from the ocean amidst a diversity of nonbeneficial bacteria, such that precise molecular communication is required for initiation of the specific relationship. Therefore it is likely there are specialized metabolites used in the light organ microenvironment to modulate these processes. To identify small molecules that may influence the establishment of this symbiosis, we used imaging mass spectrometry to analyze metabolite production in V. fischeri with altered biofilm production, which correlates directly to colonization capability in its host. “Biofilm-up” and “biofilm-down” mutants were compared to a wild-type strain, and ions that were more abundantly produced by the biofilm-up mutant were detected. Using a combination of structural elucidation and synthetic chemistry, one such signal was determined to be a diketopiperazine, cyclo(d-histidyl-l-proline). This diketopiperazine modulated luminescence in V. fischeri and, using imaging mass spectrometry, was directly detected in the light organ of the colonized host. This work highlights the continued need for untargeted discovery efforts in host-microbe interactions and showcases the benefits of the squid-Vibrio system for identification and characterization of small molecules that modulate microbiome behaviors. IMPORTANCE The complexity of animal microbiomes presents challenges to defining signaling molecules within the microbial consortium and between the microbes and the host. By focusing on the binary symbiosis between Vibrio fischeri and Euprymna scolopes, we have combined genetic analysis with direct imaging to define and study small molecules in the intact symbiosis. We have detected and characterized a diketopiperazine produced by strong biofilm-forming V. fischeri strains that was detectable in the host symbiotic organ, and which influences bacterial luminescence. Biofilm formation and luminescence are critical for initiation and maintenance of the association, respectively, suggesting that the compound may link early and later development stages, providing further evidence that multiple small molecules are important in establishing these beneficial relationships.

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Section: Resultsmentioning

confidence: 99%

“…Roles of microbial diketopiperazines. Microbial DKPs have been detailed in a number of biological contexts, including production in sexual pheromone signaling, as enzyme inhibitors, and in quorum sensing (46,(49)(50)(51). Their structures vary widely, as there are many possible amino acid combinations and side chain modifications (36).…”

Section: Resultsmentioning

confidence: 99%

A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ

Zink

Ludvik

Lazzara

et al. 2021

mBio

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“…The role of diketopiperazines in quorum sensing is currently described. These compounds could thus interact with N -acylhomoserine lactone (AHL) biosensor and in this way they can modulate bacterial characters such as bioluminescence (via LuxR from Vibrio fischeri ) [ 21 ], swarming in Serratia liquefaciens [ 22 ], pathogenicity of diverse bacteria [ 23 , 24 ], and could inhibit bacterial biofilm [ 25 ]. These types of compounds involved in cell-to-cell communications activate specific bacterial behavior by regulating the gene expression in response to bacterial density [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata—A Lichen-Associated Actinobacterium

et al. 2017

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Actinobacteria are well known for their potential in biotechnology and their production of metabolites of interest. Lichens are a promising source of new bacterial strains, especially Actinobacteria, which afford a broad chemical diversity. In this context, the culture medium of the actinobacterium Nocardia ignorata, isolated from the terrestrial lichen Collema auriforme, was studied. The strain was cultivated in a BioFlo 115 bioreactor, and the culture medium was extracted using an XAD7HP resin. Five known diketopiperazines: cyclo (l-Pro-l-OMet) (1), cyclo (l-Pro-l-Tyr) (2), cyclo (d-Pro-l-Tyr) (3), cyclo (l-Pro-l-Val) (4), cyclo (l-Pro-l-Leu) (5), and one auxin derivative: indole-carboxaldehyde (8) were isolated, along with two new brominated diketopiperazines: cyclo (d-Pro-l-Br-Tyr) (6) and cyclo (l-Pro-l-Br-Tyr) (7). Structure elucidation was performed using HRMS and 1D and 2D NMR analysis, and the synthesis of compounds 6 and 7 was carried out in order to confirm their structure.

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“…(36)(37)(38) With so many structural combinations possible, there are many more examples of DKPs that influence microbial QS systems, some in biofilm formation, and some even in Vibrio spp. (39)(40)(41)(42) Because of the relationship between biofilm production potential and appearance of 3 in the colonized host, we sought to query whether 3 affected the bioluminescence of V. fischeri. An increase in luminescence was observed at low cell densities in the WT strain (ES114) ( Figure 5).…”

Section: Role In Stimulating Bioluminescencementioning

confidence: 99%

Discovery of a microbially produced small molecule in a host-specific organ

Zink

Tarnowski

Lazzara

et al. 2020

Preprint

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The lifelong relationship between the Hawaiian bobtail squid, Euprymna scolopes, and its microbial symbiont, Vibrio fischeri, represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the hosts in a process termed counterillumination. The squid hosts hatch without their symbionts, which must be acquired from the ocean amid a diversity of non-beneficial bacteria, so precise molecular communication is required for initiation of the specific relationship. It is therefore likely that there may be specialized metabolites used in the light organ microenvironment to modulate these processes. To identify small molecules that may influence the establishment of this symbiosis, we used imaging mass spectrometry to analyze metabolite production in V. fischeri with altered biofilm production, which correlates directly to colonization capability in its host. 'Biofilm-Up' and 'Biofilm-Down' mutants were compared to a wild-type strain, and masses that were more abundantly produced by the biofilm-up mutant were detected. Using a combination of structure elucidation and synthetic chemistry, one such signal was determined to be a diketopiperazine, cyclo(D-histidyl-L-proline). This diketopiperazine modulated luminescence in V. fischeri and, using label-free imaging mass spectrometry, was directly detected in the light organ of the colonized host. This work highlights the continued need for untargeted discovery efforts in host-microbe interactions and showcases the benefits of the squid-Vibrio system for identification and characterization of small molecules that modulate microbiome behaviors.

show abstract

Inhibition of biofilm in Bacillus amyloliquefaciens Q-426 by diketopiperazines

Cited by 13 publications

References 55 publications

A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ

A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ

Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata—A Lichen-Associated Actinobacterium

Discovery of a microbially produced small molecule in a host-specific organ

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