MASHIMA Izumi

NAKAZAWA Futoshi

English

MASHIMA, Izumi

33560

NAKAZAWA, Futoshi

33570

Health Sciences University of Hokkaido Academic Repository / 北海道医療大学学術リポジトリ

北海道医療大学学術リポジトリThe Beginning of Application of QuorumQuenching for Replacing TraditionalAntibiotics著者 MASHIMA Izumi, NAKAZAWA Futoshijournal orpublication titleThe dental journal of Health SciencesUniversity of Hokkaidovolume 33number 2page range 13-16year 2014-12-31URL http://id.nii.ac.jp/1145/00010221/?????? ??????? ??? ???????????It has been cleared that bacterial cell can communicatewith each other and respond to a changing environment. Thecell-cell communication system known as quorum sensing(QS) plays essential roles in regulating gene expression andfunctional adjustment among bacterial communities asshown in Figure 1. The QS bacteria release, detect and re-spond to accumulation of small signal molecules in a celldensity-dependent manner for regulating the expression oftarget genes. Several signals for bacterial cell-cell communi-cation have been identified previously, such as acyl ho-moserine lactone ( AHL ) , cyclic thiolactone, hydroxyl-palmitic acid methyl ester, furanosylborate and methy dode-cenoic acid.Among these signals, AHLs called as autoinducer-1 (AI-1) are the best-characterized cell-cell communication signals.And more than a dozen AHL derivatives have been identi-fied in range of Gram-negative bacterial species, which varyin length or substitution at the acyl side chain. And, it hasbeen reported that these AHL signals are involved in theregulation of important biological functions, antibiotic pro-duction, motility, production of virulence factors and biofilmformation. Still there are many bacterial species known toproduce AHL signals, but the corresponding biological func-tions remain to be un-cleared.Also, autoinducer-2 (AI-2) has been determined as mem-ber of extracellular signaling molecules used in QS. AI-2 isa furanosyl borate diester derived from the recycling of S-adenosyl-homocystein. AI-2, originally discovered in the QS????? ?????????? ????????? ?? ??????????? ?? ?????? ???????????? ????????? ??????????? ???????????Izumi MASHIMA, Futoshi NAKAZAWADepartment of Oral Microbiology, School of Dentistry, Health Sciences University of Hokkaido??? ??????Quorum sensing, Quorum quenching, Autoinducer, AHL, Clinical application????????Communication among bacteria is achieved via theproduction, detection and response to chemical signal-ing molecules, such as N-acyl homoserine lactones(AHLs) known as autoinducers (AI). Detected AIs leadto quorum sensing (QS) gene regulation, when a thresh-old concentration of them is reached. It is known thatthe QS with AIs regulates bacterial virulence factors,antibiotic production and biofilm formation. Recently,the AHL-degradation enzymes and QS-inhibitors havebeen identified in a range of living bacteria and plants.Interfering with the QS system, quorum quenching(QQ), has been suggested as a potential strategy forcontrol of infectious disease. In this review, we discussthe function of QQ enzymes and QS-inhibitors for hostdiseases and their application in resistance against mi-crobial diseases.??????????? ??????????????Figure 1 : Quorum sensing system of AHL type.??????????????????????????????????????????????????????????????????????????????????????????????????bacterium Vibrio harveyi , is made by many species of Gram-negative and Gram-positive bacteria. In every case, produc-tion of AI-2 is dependent on the LuxS autoinducer synthase.Also, AI-2 is a species-nonspecific signal used by bothGram-negative and Gram-positive bacteria. And, it is re-ported that AI-2 has been found to influence biofilm forma-tion in a mixed-species biofilm between Streptococcus gor-donii and Porphyromonas gingivalis.Dental plaque has been known to be three-dimensionaloral biofilm. And it is reported that oral Veillonella speciesas the early colonizers play important roles at the early stageof oral biofilm formation with Streptococcus species as theinitial colonizers. Recently, it is confirmed that Veillonellatobetsuensis, established in our laboratory in 2013, produceAI-1 and AI-2 in the culture supernatant, and these AIs mayregulate biofilm formation with Streptococcus gordonii.?????? ????????? ??????Over the past decade, a range of quorum quenching (QQ)enzymes and inhibitors have been identified from differentsources, including prokaryotic and eukaryotic organisms asshown in Figure 2.It is known partially that these QQ enzymes attenuate theeffectiveness of the QS signal molecule, render the QSmolecule incapable of binding to target regulator, affect thespecificity and recognition of the AHL signal, or disturb theactivation of the QS-mediated genes regulated by AHLs.These enzymes and inhibitors are the key molecules forestablishing the concept of QQ, anti-pathogenic and signalinterference. But, a limited number of QQ enzymes that in-terfere with bacterial QS molecules are known, although themechanisms of the QS system are well understood.The QQ enzyme for AHLs may be grouped into threetypes based on degradation pattern of AHLs. (1) Lactonasecleaves the molecule AHLs to open the homoserine lactonering as shown in Figure 3(1). These lactonases, such as AiiA(Riaz et al., 2008) and AttM (Uroz et al., 2008), are Zn2+-dependent lactonases that produced in the genera Bacillusand Agrobacterium . (2) Acylase hydrolyzes the amide link-age between homoserine moiety and acyl chain, and releaseshomoserine lactone and fatty acid as shown in Figure 3(2).Previously, various acylases have been reported includingAiiD in Ralstonia , AhlM in Streptomyces and AiiC in An-abaena (Dong et al., 2001). (3) Oxidoreductase catalyzesmodification of the chemical structure of the acyl side chainbut not degradation as shown in Figure 3(3). It is reportedthat Bacillus (Chowdhary et al., 2007), Pseudomonas (Bi-jtenhoorn et al., 2011) and Rhodococcus (Uroz et al., 2005)produce these kind of oxidoreductases.Recently, the interfering with microbial QS system by QQhas been suggested as a novel strategy for control of infec-tious disease because QQ aims to shut down the virulenceexpression in pathogenic bacteria rather than restrict cellgrowth. Although the roles of QQ enzymes in native envi-ronments are not always certain, their ability and availabilityin potential therapeutic applications are prospective, consid-erably.?????? ??????? ????????? ???? ??????? ??????Although there are some chemically synthesized QS in-hibitors, many inhibitors have been discovered in naturalplants extracts. Because plants are constantly exposed tobacterial infections like humans and animals, it makes senseto expect that plants have developed good chemical and/orphysiological mechanisms to combat pathogenic bacteria.Furthermore, since the plants, such as vegetables, can beconsumed by humans, the compounds having QS inhibitoryactivity from the natural plant products may be deemed asIzumi MASHIMA et al.?The Beginning of Application of Quorum Quenching for Replacing Traditional AntibioticsFigure 2 : The effects of Quorum quenching (QQ) enzymes andinhibitors.Figure 3 : Basic structure of AHL and patterns of degradation byQQ enzyme??????????????????????????????????????????????????????????????????????????????????????????????????safe may not cause toxicity against human cells. Of coursetoxicity studies on the components are indispensable beforeuse.One of the most extensively studied natural products isAustralian seaweed as known Delisea pulchra (Manefield etal., 1999). This seaweed appears to be able to inhibit bacte-rial colonization by interfering with the AHL system. Halo-genated furanones from D. pulchra inhibit the QS regulatedreactions by competitively bind to the LuxRs that are recep-tor proteins for AHLs. It is also demonstrated that the fura-nones are strong inhibitors for both AI-1 and AI-2-mediatedQS systems and the inhibition is partially relieved accordingto increase of AHL concentration (Manefield et al., 2002).Recently, it is reported that a non-competitive compound,malabaricone C, which is extracted from nutmeg (Myristicacinnamomea ) and is not similar to AHL in structure, inhibitthe QS system in Pseudomonas aeruginosa (Ganin et al. ,2013). Also, vegetables including carrot, chamomile, waterlily and pepper have been proven to have anti-QS activity.??????????? ?? ?????? ????????? ??? ??????????????????Due to the extensive emergence of antibiotic-resistantstrains of bacteria, the exploitable drugs to treat bacterial in-fections have become circumscribed considerably. Therefore,the search for novel antibacterial therapy is important andhas received greater attention.Under this severe condition, QQ may be used to controlinfectious disease in a QS system by triggering the patho-genic pattern. Since the QQ strategy does not intend to killthe pathogen or reduce bacterial cell, but to shut down theexpression of pathogenic genes, the intercept with the QSsystem by QQ enzyme or QS inhibitor is a potential strategyinstead of conventional antibiotics. That is to say, the subsis-tent of QQ enzyme or QS inhibitor in QS system can turndown their QS, leading to blocking disadvantageous geneexpression.Up to now, two strategies have been reported as noveltherapeutic tools for controlling infectious disease. (1) In aco-culture of QS-dependent pathogens, the QQ enzymes pro-duced by QQ microbes and/or QS inhibitors extracted fromplants could limit the accumulation of QS signal molecules,resulting in a significant reduction in QS-mediated infection.(2) When QQ enzymes and/or QS inhibitors were challengedwith QS-mediated pathogen, the enzymes and/or inhibitorsshowed an elevated tolerance to the pathogen.Dental plaque is a typical natural biofilm causing oral in-fectious disease, such as dental caries and periodontal dis-ease. Biofilm infection is difficult to exterminate because ofits protection against antibiotics and macrophages comparedwith planktonic cells. The QS signal molecule has beenshown to mediate biofilm formation to protect against antibi-otics.Since it was also shown previously that acylase I, one ofQQ enzyme, reduced significantly the biofilm formation byenvironmental strains of bacteria, it may be possible to con-trol oral biofilm formation at an early stage using QQ en-zymes or QQ inhibitors, leading to establish a novel preven-tative method for dental caries and periodontal diseases. Ac-tually, grapefruit extract contains bioactive compounds suchas furocoumarins, limonoids and coumarin that have antibac-terial activity. Also, the furocoumarins were shown to havestrong inhibition against AI-1 and AI-2 activities, as well ashinder the formation of biofilm. In addition to that,obacunone, contained in many plants as one of limonoids,has been proven to have strong activity as QS inhibitoragainst both AHL and AI-2 systems and biofilm formation.In the future, the external addition of the QQ enzymes orQS inhibitors may represent a novel general antibacterialtherapy, especially against antibiotic-resistant strains of bac-teria, and highlights the potential value of QQ enzymes andQS inhibitors to protect against bacterial infection.????????????????We appreciate Professor Taishin TAKUMA, Chief Editorof The Dental Journal of Health Sciences University of Hok-kaido, for giving a chance to publish this article.??????????Bijtenhoorn P, Mayerhofe H, Muller0Dieckman J, UtpatelC, Schippe C Hornung C, Szesny M, Grond S, ThurmerA, Brzuszkiewicz E. A novel metagenomic shot-chaindehydrigenase/reductase attenuates Pseudomonas aerugi-nosa biofilm formation and virulence on Caenorhabditiselegans. PLOS one 6 : e26278, 2011.Chowdhary PK, Keshavan N, Nguyen HQ, Peterson JA,Gonzalez JE, Haines DC. Bacillus megaterium CYP102A1 oxidation of acyl homoserine lactones and acyl ho-moserines. Biochem 46 : 14429-14437, 2007.Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF, ZhangThe Dental Journal of Health Sciences University of Hokkaido 33 2014 ??????????????????????????????????????????????????????????????????????????????????????????????????LH. Quenching quorum-sensing-dependent bacterial in-fection by an N-acyl homoserine lactonase. Nature 411 :813-817, 2001.Ganin H, Rayo J, Amara N, Levy N, Krief P, Meijler MM.Sulforaphane and erucin, natural isothiocyanates frombroccoli, inhibit bacterial quorum sensing. Med ChemCommun 4 : 175-179, 2013.Manefield M, de Nys R, Kumar N, Read R, Givskov M,Steinberg P, Kjelleberg S. Evidence that halogenated fu-ranones from Delisea pulchra inhibit acylated homoser-ine lactone (AHL)-mediated gene expression by displac-ing the signal from its receptor protein. Microbiol 145 :283-291, 1999.Manefield M, Rasmussen TB, Henzter M, Andersen JB,Steinberg P, Givskov M. Halogenated furanones inhibitquorum sensing through accelerated LuxR turnover. Mi-crobiol 148 : 1119-1127, 2002.Riaz K, Elmerich C, Moreira D, Raffoux A, Dessaux Y,Faure D. Ametagenomic analysis of soil bacteria extendsdiversity of quorum-quenching lactonases. Environ Mi-crobiol 10 : 560-570, 2008.Uroz S, Chhabra SR, Camara M, William P, Oger PM,Dessaux Y. A-acylhomoserine lactone wuorum-sensingmolecules are modified and degraded by Rhodococcuserythropolis W2 by both amidolytic and novel oxidore-ductase activity. Microbiol 151 : 3313-3322, 2005.Uroz S, Oger PM,Chapelle E, Adeline MT, Faure D, Des-saux Y. A Rhodococcus qsdA-encoded enzyme defines anovel class of large-spectrum quorum-quenching lacto-nases. Appl Environ Microbiol 72 : 1357-1366, 2008.?? ??????????????????????????????????????? ???????? ????????? ????????????? ????????? ????????????? ????????? ??????????????? ????????? ??????????????? ???Izumi MASHIMA et al.?The Beginning of Application of Quorum Quenching for Replacing Traditional Antibiotics??????????????????????????????????????????????????????????????????????????????????????????????????

The Beginning of Application of Quorum Quenching for Replacing Traditional Antibiotics

https://hsuh.repo.nii.ac.jp/?action=repository_action_common_download&item_id=10262&item_no=1&attribute_id=22&file_no=1

The Beginning of Application of Quorum Quenching for Replacing Traditional Antibiotics

Abstract

Similar works

Full text

Available Versions

Health Sciences University of Hokkaido Academic Repository / 北海道医療大学学術リポジトリ