• Molecules and Cells
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• 제28권5호
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• pp.447-453
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• 2009

The quorum sensing (QS) inhibitors that antagonize TraR, a receptor protein for N-3-oxo-octanoyl-L-homoserine lactones (3-oxo-C8-HSL), a QS signal of Agrobacterium tumefaciens were developed. The structural analogues of 3-oxo-C8-HSL were designed by in silico molecular modeling using SYBYL packages, and synthesized by the solid phase organic synthesis (SPOS) method, where the carboxamide bond of 3-oxo-C8-HSL was replaced with a nicotinamide or a sulfonamide bond to make derivatives of N-nicotinyl-L-homoserine lactones or N-sulfonyl-L-homoserine lactones. The in vivo inhibitory activities of these compounds against QS signaling were assayed using reporter systems and compared with the estimated binding energies from the modeling study. This comparison showed fairly good correlation, suggesting that the in silico interpretation of ligand-receptor structures can be a valuable tool for the pre-design of better competitive inhibitors. In addition, these inhibitors also showed anti-biofilm activities against Pseudomonas aeruginosa.

• Membrane and Water Treatment
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• 제14권1호
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• pp.35-45
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• 2023

Biofilms significantly affect the performance of wastewater treatment processes in which biodegradability of numerous microorganisms are actively involved, and various technologies have been applied to secure microbial biofilms. Understanding changes in biofilm characteristics by regulating expression of signaling molecules is important to control and regulate biofilms in membrane bioreactor, i.e., biofouling. This study investigated effects of addition of acyl-homoserine lactones (AHL) as a controllable factor for the microbial signaling system on biofilm formation of Pseudomonas aeruginosa PAO1 and multiple strains in membrane bioreactor. The addition of three AHL, i.e., C4-, C6-, and C8-HSL, at a concentration of 200 ㎍/L, enhanced the formation of the PAO1 biofilm and the degree of increases in the biofilm formation of PAO1 were 70.2%, 76.6%, and 72.9%, respectively. The improvement of biofilm formation of individual strains by C4-HSL was an average of 68%, and the microbial consortia increased by approximately 52.1% in the presence of 200 ㎍/L C4-HSL. CLSM images showed that more bacterial cells were present on the membrane surface after the AHL application. In the COMSTAT results, biomass and thickness were increased up to 2.2 times (PAO1) and 1.6 times (multi-strains) by C4-HSL. This study clearly showed that biofilm formation was increased by the application of AHL to individual strain groups, including PAO1 and microbial consortia, and significant increases were observed when 50 or 100 ㎍/L AHL was administered. This suggests that AHL application can improve the biofilm formation of microorganisms, which could yield an enhancement in efficiency of biofilm control, such as in various biofilm reactors including membrane bioreactor and bioflocculent systems in water/wastewater treatment processes.

• Journal of Microbiology and Biotechnology
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• 제21권12호
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• pp.1330-1335
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• 2011

N-Acyl homoserine lactones (AHLs) serve as the vital quorum-sensing signals that regulate the virulence of the pathogenic bacterium Erwinia carotovora. In the present study, an approach to efficiently restrain the pathogenicity of E. carotovora-induced soft rot disease is described. Bacillus thuringiensis-derived N-acyl homoserine lactonase (AiiA) was projected onto the surface of Pseudomonas putida cells, and inoculation with both strains was challenged. The previously identified N-terminal moiety of the ice nucleation protein, InaQ-N, was applied as the anchoring motif. A surface display cassette with inaQ-N/aiiA was constructed and expressed under the control of a constitutive promoter in P. putida AB92019. Surface localization of the fusion protein was confirmed by Western blot analysis, flow cytometry, and immunofluorescence microscopy. The antagonistic activity of P. putida MB116 expressing InaQ-N/AiiA toward E. carotovora ATCC25270 was evaluated by challenge inoculation in potato slices at different ratios. The results revealed a remarkable suppressing effect on E. carotovora infection. The active component was further analyzed using different cell fractions, and the cell surface-projected fusion protein was found to correspond to the suppressing effect.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권4호
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• pp.322-328
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• 2005

Acylhomoserine lactones (AHLs) are known to be the triggering molecules in the quorum sensing mechanism of many gram-negative bacteria. In order to detect AHL inhibitors that are potential biofilm inhibitors, a convenient and sensitive bioassay was developed based on the $\beta$-galactosidase activity ($\beta$-GAL) of a recombinant Agrobacterium tumefaciens strain. A series of commercially available AHLs were tested for inducing $\beta$-GAL at varying concentrations in agar-plate and liquid cultures of the reporter strain. All AHLs tested exhibited a concentration­dependent induction, and octanoyl homoserine lactone (OHL) showed the highest sensitivity with a detection limit of 0.1 nM in the liquid culture assay. When fimbrolide, a known quorum sensing inhibitor, was added, induction of $\beta$-GAL by OHL was repressed. The repression at a constant OHL concentration was dependent on the fimbrolide concentration with the detection limit below 1 ppm, indicating that this assay is a sensitive method for screening AHL inhibitors.

• 한국미생물·생명공학회지
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• 제50권1호
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• pp.1-14
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• 2022

Bacteria communicate with each other through an intricate communication mechanism known as quorum sensing (QS). QS regulates different behavioral aspects in bacteria, such as biofilm formation, sporulation, virulence gene expression, antibiotic production, and bioluminescence. Several different chemical signals and signal detection systems play vital roles in promoting highly efficient intra- and interspecies communication. Gram-negative bacteria coordinate gene regulation through the production of acyl homoserine lactones (AHLs). Gram-positive bacteria do not code for AHL production, while some gram-negative bacteria have an incomplete AHL-QS system. Despite this fact, these microbes can detect AHLs owing to the presence of LuxR solo receptors. Various studies have reported the role of AHLs in interspecies signaling. Moreover, as bacteria live in a polymicrobial community, the production of extracellular compounds to compete for resources is imperative. Thus, AHL-mediated signaling and inhibition are considered to affect virulence in bacteria. In the current review, we focus on the synthesis and regulation mechanisms of AHLs and highlight their role in interspecies bacterial signaling. Exploring interspecies bacterial signaling will further help us understand host-pathogen interactions, thereby contributing to the development of therapeutic strategies intended to target chronic polymicrobial infections.

• 생명과학회지
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• 제26권12호
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• pp.1487-1497
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• 2016

정족수 인식 체계라 불리는 세균들의 세포간 의사교환 전략은 다양한 유전자의 발현조절을 통해, 생물막 성숙, 세포 외 고분자물질의 생산, 병원성 발현 및 항생제 생산 등과 같은 다양한 표현형을 조절하는 세균의 다세포성 행동 양식을 제어한다. 다수의 연구에 의하면 많은 종류의 그람 (Gram)음성 세균들이 정족수 인식체계에 필요한 신호전달 물질로 acyl-homoserine lactones (AHLs)를 사용하고 있으며, 이들은 생물막 형성에 중요한 인자로 작용함을 시사하였다. 이러한 정족수 인식체계에 의한 생물막의 형성은 물이 존재하는 모든 표면환경에서 불필요한 바오매스 축적이라는 심각한 기술적, 경제적 문제를 초래하고 있다. 최근 정족수 인체 체계를 교란하는 다수의 물질들이 다양한 미생물로부터 발견되어, 그들의 정족수 인식 체계와 관련된 주요 기능과 기작들이 밝혀지고 있다. 이러한 정족수 제어 물질들은 최근 다양한 산업에서 발생하는 생물 부착현상들을 제어할 수 있는, 환경 친화적이며 세균의 항생제 다재 내성을 완화 시킬 수 있는 새로운 방법으로 대두되고 있다. 따라서 본 논문은 세균의 정족수 인식 체계와 관련된 최근 정보, 정족수 인식 신호를 제어할 수 있는 정족수 제어 효소와 이러한 기술을 이용한 생물 부착 저해 방법 등을 논의하고자 한다.

• Animal Bioscience
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• 제37권2_spc호
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• pp.337-345
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• 2024

Ruminants possess a specialized four-compartment forestomach, consisting of the reticulum, rumen, omasum, and abomasum. The rumen, the primary fermentative chamber, harbours a dynamic ecosystem comprising bacteria, protozoa, fungi, archaea, and bacteriophages. These microorganisms engage in diverse ecological interactions within the rumen microbiome, primarily benefiting the host animal by deriving energy from plant material breakdown. These interactions encompass symbiosis, such as mutualism and commensalism, as well as parasitism, predation, and competition. These ecological interactions are dependent on many factors, including the production of diverse molecules, such as those involved in quorum sensing (QS). QS is a density-dependent signalling mechanism involving the release of autoinducer (AIs) compounds, when cell density increases AIs bind to receptors causing the altered expression of certain genes. These AIs are classified as mainly being N-acyl-homoserine lactones (AHL; commonly used by Gram-negative bacteria) or autoinducer-2 based systems (AI-2; used by Gram-positive and Gram-negative bacteria); although other less common AI systems exist. Most of our understanding of QS at a gene-level comes from pure culture in vitro studies using bacterial pathogens, with much being unknown on a commensal bacterial and ecosystem level, especially in the context of the rumen microbiome. A small number of studies have explored QS in the rumen using 'omic' technologies, revealing a prevalence of AI-2 QS systems among rumen bacteria. Nevertheless, the implications of these signalling systems on gene regulation, rumen ecology, and ruminant characteristics are largely uncharted territory. Metatranscriptome data tracking the colonization of perennial ryegrass by rumen microbes suggest that these chemicals may influence transitions in bacterial diversity during colonization. The likelihood of undiscovered chemicals within the rumen microbial arsenal is high, with the identified chemicals representing only the tip of the iceberg. A comprehensive grasp of rumen microbial chemical signalling is crucial for addressing the challenges of food security and climate targets.

• The Plant Pathology Journal
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• 제27권3호
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• pp.242-248
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• 2011

Several soil bacteria were found to degrade N-Acylhomoserine lactones (NAHLs), thereby interfering with the bacterial quorum sensing system. In this research, fifteen strains of NAHL degrading rhizobacteria were isolated from potato rhizosphere. Based on phenotypic characteristics and 16S rDNA sequence analyses, the strains were identified as members of genera Bacillus, Streptomyces, Arthrobacter, Pseudomonas and Mesorhizobium. All tested isolates were capable to degrade both synthetic and natural NAHL produced by Pectobacterium carotovorum subsp. carotovorum (Pcc) strain EMPCC. In quorum quenching experiments selected isolates, especially Mesorhizobium sp., were markedly reduced the pathogenicity of Pcc strain EMPCC in potato tubers and totally suppressed tissue maceration on potato tubers. These led to consider the latter as a useful biocontrol agent against Pectobacterium spp.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.411-414
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• 2002

Acylated homoserine lactones (AHLs) are membrane-permeant signal molecules responsible for biofilm formation of gram-negative bacteria via a unique mechanism known as quorum sensing. A target specific bioassay employing the AHL-responsive Agrobacterium tumefaciens reporter strain has been developed to identify new AHL-like compounds from natural products, which could be developed into antifouling compounds. By varying the X-gal concentration, incubation time, solvent for sample preparation and the sample loading procedure, it was possible to detect low level AHLs up to $10^1nM$. The length of the acyl chain of the AHLs was found to affect the sensitivity of this bioassay.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.224.1-224.1
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• 2003

Recent studies have revealed that bacterial biofilm production by the gram-negative bacteria is regulated by the quorum sensing signaling molecules, AHLs (N-acyl homoserine lactones). This suggests that inhibiting the AHLs could enhance the effects of antibacterial agents. Halogenated furanones purified from the red algae Delisea pulchra have been known to decrease quorum sensing responses by competitive inhibition of the AHLs. (omitted)