ebook img

Low-dose antibiotics PDF

169 Pages·2017·12.84 MB·English
by  
Save to my drive
Quick download
Download
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.

Preview Low-dose antibiotics

Downloaded from orbit.dtu.dk on: Feb 07, 2023 Low-dose antibiotics: current status and outlook for the future Nosanchuk, Joshua D.; Lin, Jun; Hunter, Robert P.; Aminov, Rustam Link to article, DOI: 10.3389/978-2-88919-355-4 Publication date: 2014 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Nosanchuk, J. D., Lin, J., Hunter, R. P., & Aminov, R. (Eds.) (2014). Low-dose antibiotics: current status and outlook for the future. Frontiers Media SA. Frontiers Research Topics https://doi.org/10.3389/978-2-88919-355-4 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.  Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LOW-DOSE ANTIBIOTICS: CURRENT STATUS AND OUTLOOK FOR THE FUTURE Topic Editors Joshua D. Nosanchuk, Jun Lin, Robert P. Hunter and Rustam I. Aminov MICROBIOLOGY PUBLIC HEALTH FRONTIERS COPYRIGHT ABOUT FRONTIERS STATEMENT © Copyright 2007-2014 Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering Frontiers Media SA. approach to the world of academia, radically improving the way scholarly research is managed. All rights reserved. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share All content included on this site, such as text, graphics, logos, button icons, images, and generate knowledge. Frontiers provides immediate and permanent online open access to all video/audio clips, downloads, data its publications, but this alone is not enough to realize our grand goals. compilations and software, is the property of or is licensed to Frontiers Media SA (“Frontiers”) or its licensees and/or subcontractors. The copyright in the text of individual articles is the property of their FRONTIERS JOURNAL SERIES respective authors, subject to a license granted to Frontiers. The Frontiers Journal Series is a multi-tier and interdisciplinary set of open-access, online The compilation of articles constituting journals, promising a paradigm shift from the current review, selection and dissemination this e-book, wherever published, as well processes in academic publishing. as the compilation of all other content on this site, is the exclusive property of All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service Frontiers. For the conditions for to the scholarly community. At the same time, the Frontiers Journal Series operates on a revo- downloading and copying of e-books from Frontiers’ website, please see the Terms lutionary invention, the tiered publishing system, initially addressing specific communities of for Website Use. If purchasing Frontiers scholars, and gradually climbing up to broader public understanding, thus serving the interests e-books from other websites or sources, the conditions of the website concerned of the lay society, too. apply. Images and graphics not forming part of user-contributed materials may not be downloaded or copied without DEDICATION TO QUALITY permission. Individual articles may be downloaded Each Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interac- and reproduced in accordance with the tions between authors and review editors, who include some of the world’s best academicians. principles of the CC-BY licence subject to any copyright or other notices. They may Research must be certified by peers before entering a stream of knowledge that may eventually not be re-sold as an e-book. reach the public - and shape society; therefore, Frontiers only applies the most rigorous and As author or other contributor you grant a unbiased reviews. CC-BY licence to others to reproduce your articles, including any graphics and Frontiers revolutionizes research publishing by freely delivering the most outstanding research, third-party materials supplied by you, in evaluated with no bias from both the academic and social point of view. accordance with the Conditions for Website Use and subject to any copyright By applying the most advanced information technologies, Frontiers is catapulting scholarly notices which you include in connection publishing into a new generation. with your articles and materials. All copyright, and all rights therein, are protected by national and international copyright laws. WHAT ARE FRONTIERS RESEARCH TOPICS? The above represents a summary only. For the full conditions see the Conditions Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are for Authors and the Conditions for collections of at least ten articles, all centered on a particular subject. With their unique mix Website Use. Cover image provided by Ibbl sarl, of varied contributions from Original Research to Review Articles, Frontiers Research Topics Lausanne CH unify the most influential researchers, the latest key findings and historical advances in a hot ISSN 1664-8714 research area! ISBN 978-2-88919-355-4 Find out more on how to host your own Frontiers Research Topic or contribute to one as an DOI 10.3389/978-2-88919-355-4 author by contacting the Frontiers Editorial Office: [email protected] December 2014 | Low-dose antibiotics: current status and outlook for the future | 1 LOW-DOSE ANTIBIOTICS: CURRENT STATUS AND OUTLOOK FOR THE FUTURE Topic Editors: Joshua D. Nosanchuk, Albert Einstein College of Medicine, USA Jun Lin, The University of Tennessee, USA Robert P. Hunter, Parnell Pharmaceuticals, USA Rustam I. Aminov, Technical University of Denmark, Denmark Antimicrobial therapy is a key factor in our success against pathogens poised to ravage at risk or infected individuals. However, we are currently at a watershed point as we face a growing crisis of antibiotic resistance among diverse pathogens. One area of intense interest is the impact of the application of antibiotics for uses other than the treatment of patients and the association with such utilization with emerging drug resistance. This Research Topic “Low- dose antibiotics: current status and outlook for the future” in Frontiers in Microbiology: Antimicrobials, Resistance and Chemotherapy details various aspects of the wide ranging effects of antimicrobial therapy from areas such as the regulation of host responses to modulation of bacterial virulence factors to acquisition of antibiotic resistance genes. December 2014 | Low-dose antibiotics: current status and outlook for the future | 2 Table of Contents 05 Low-Dose Antibiotics: Current Status and Outlook for the Future Joshua D. Nosanchuk, Jun Lin, Robert P. Hunter and Rustam I. Aminov 07 Biotic Acts of Antibiotics Rustam I. Aminov 23 Antivirulence Activity of Azithromycin in Pseudomonas Aeruginosa Francesco Imperi, Livia Leoni and Paolo Visca 30 Responses of Pseudomonas Aeruginosa to Antimicrobials Yuji Morita, Junko Tomida and Yoshiaki Kawamura 38 Biofilm Formation of Clostridium Perfringens and its Exposure to Low-Dose Antimicrobials Audrey Charlebois, Mario Jacques and Marie Archambault 49 The Impact of Antifungals on Toll-Like Receptors Mircea R. Mihu, Rodney Pattabhi and Joshua D. Nosanchuk 54 Biotic Activity of Ca2+- Modulating Non-Traditional Antimicrobial and -Viral Agents Kevin B. Clark 58 Interplay Between Policy and Science Regarding Low-Dose Antimicrobial Use in Livestock Amanda C. Sorensen, Robert S. Lawrence and Meghan F. Davis 61 Obesity in the United States – Dysbiosis From Exposure to Low-Dose Antibiotics? Lee W. Riley, Eva Raphael and Eduardo Faerstein 69 Antibiotic Alternatives: The Substitution of Antibiotics in Animal Husbandry? Guyue Cheng, Haihong Hao, Shuyu Xie, Xu Wang, Menghong Dai, Lingli Huang and Zonghui Yuan 84 Use of Antibiotics as Feed Additives: A Burning Question Madhab K. Chattopadhyay 87 Benefits and Risks of Antimicrobial Use in Food-Producing Animals Haihong Hao, Guyue Cheng, Zahid Iqbal, Xiaohui Ai, Hafiz I. Hussain, Lingli Huang, Menghong Dai, Yulian Wang, Zhenli Liu and Zonghui Yuan 98 Carbadox has Both Temporary and Lasting Effects on the Swine Gut Microbiota Torey Looft, Heather K. Allen, Thomas A. Casey, David P. Alt and Thaddeus B. Stanton December 2014 | Low-dose antibiotics: current status and outlook for the future | 3 107 Antibiotics in Canadian Poultry Productions and Anticipated Alternatives Moussa S. Diarra and François Malouin 122 Perspectives in the Use of Tannins as Alternative to Antimicrobial Growth Promoter Factors in Poultry Leandro M. Redondo, Pablo A. Chacana, Johana E. Dominguez and Mariano E. Fernandez Miyakawa 129 Antibiotic Growth Promoters Enhance Animal Production by Targeting Intestinal Bile Salt Hydrolase and its Producers Jun Lin 133 Learning From Agriculture: Understanding Low-Dose Antimicrobials as Drivers of Resistome Expansion Yaqi You and Ellen K. Silbergeld 143 Antibiotics Promote Aggregation within Aquatic Bacterial Communities Gianluca Corno, Manuela Coci, Marco Giardina, Sonia Plechuk, Floriana Campanile and Stefania Stefani 152 Evolution in Action: Dissemination of tet(X) into Pathogenic Microbiota Rustam I. Aminov 156 Genomic Interplay in Bacterial Communities: Implicationsfor Growth Promoting Practices in Animal Husbandry Piklu Roy Chowdhury, Jessica McKinnon, Ethan Wyrsch, Jeffrey M. Hammond, Ian G. Charles and Steven P. Djordjevic December 2014 | Low-dose antibiotics: current status and outlook for the future | 4 EDITORIAL published:10September2014 doi:10.3389/fmicb.2014.00478 Low-dose antibiotics: current status and outlook for the future JoshuaD.Nosanchuk1,2*,JunLin3,RobertP.Hunter4 andRustamI.Aminov5 1DepartmentofMedicine,AlbertEinsteinCollegeofMedicineofYeshivaUniversity,Bronx,NY,USA 2DepartmentofMicrobiologyandImmunology,AlbertEinsteinCollegeofMedicineofYeshivaUniversity,Bronx,NY,USA 3DepartmentofAnimalScience,TheUniversityofTennessee,Knoxville,TN,USA 4ParnellPharmaceuticals,OverlandPark,KS,USA 5SectionforBacteriology,Pathology,andParasitology,NationalVeterinaryInstitute,TechnicalUniversityofDenmark,Frederiksberg,Denmark *Correspondence:[email protected] Editedby: KunihikoNishino,OsakaUniversity,Japan Reviewedby: YujiMorita,AichiGakuinUniversity,Japan ManuelaCoci,NationalResearchCouncil,Italy Keywords:antibiotics,lowdoseantibiotics,immunomodulatoryeffect,environmentalimpact,growthpromotion,feedadditives Antimicrobial therapy is a key factor in our success against effector pathways with antimicrobials, Mihu et al. detail how pathogens poised to ravage at risk or infected individuals. antifungal medications effectively stimulate host responses via However, we are currently at a watershed point as we face a engagement with toll-like receptors (Mihuet al.,2014).In light growing crisisofantibiotic resistance amongdiverse pathogens. of the expanding difficulties with drug resistance and a lack of One area of intense interest is the impact of the application of therapeutics to combat them, Clark presents a cogent call for antibiotics for uses other than the treatment of patients and pursing Ca2+ modulating strategies where by host Ca2+ home- the association with such utilization with emerging drug resis- ostasisismodulatedtoblockpathogensfromeffectivelyutilizing tance. This Research Topic “Low-dose antibiotics: current sta- thisessentialelement(Clark,2013). tus and outlook for the future” in Frontiers in Microbiology: An important focus in this Research Topic is the use Antimicrobials, Resistance, and Chemotherapy details various of antibiotics as growth enhancers in animals. Sorensen and aspectsofthewiderangingeffectsofantimicrobialtherapyfrom colleagues provide key insights into the effects of scientific areas such as the regulation of host responses to modulation of evidenceonthepolicydecisionsontheuseoflow-doseantimi- bacterial virulence factors to acquisition of antibiotic resistance crobials in livestock for growth promotion and disease preven- genes. tion particularly delineating how data have led to the European Aremarkableandoftenoverlookedfundamentalofantibiotics Union’s ban of low-dose antimicrobials whereas their use in isthattheyhavebiologicalactivitiesbeyondmicrobialkilling.The the United States of America remains in flux (Sorensen et al., host modulatory aspects of macrolides, tetracyclines, and beta- 2014).Thebottomlineisthatthereisanurgentneedtodevelop lactamsarereviewedbyAminov(2013a)underscoringhow,for policy based on well derived data, with this data being eas- example,macrolidessuchasazithromycinareroutinelyusedfor ily and widely available to independent parties. The articles by immunomodulationinpatientswithchronicpulmonarydisease Chengetal.(2014),Chattopadhyay(2014),andHaoetal.(2014) ratherthanforanantimicrobialeffect.Azithromycinisalsoused all further underscore critically important facets of the contin- asatoolbyImperietal.todetailhownon-conventionalthinking ued utilization of antibiotics in animal husbandry. Looft and about regulating virulence factors or modifying host inflamma- colleagues detail their research on how the use of the in-feed tory cascades are useful to combating major pathogens such as antibiotic carbadox cases dramatic short- and long-term effects Pseudomonas aeruginosa (Imperi et al., 2014). Along this line, onthecompositionofporcinegutmicrobiota(Looftetal.,2014). Morita and colleagues carefully detail the pleotropic responses Diarra and Malouin specifically describe the impact of antibi- ofP.aeruginosatosub-therapeuticlevelsofseveralantibacterials otics in Canadian poultry production and describe the use of andproposeavenuestopursuetocombatthispathogen,suchas alternatives, such as bioactive molecules from cranberries, that developingeffluxpumpinhibitors(Moritaetal.,2014).Intheir shouldnotdriveantibioticresistance(DiarraandMalouin,2014). article, Charlebois et al. show Clostridium perfringens biofilm Similarly,Rendondoetal.providethoughtfulinsightsintotheuse can be regulated by certain antibiotics at low concentrations oftannins inlieu ofantibiotics for improving health in poultry (Charleboisetal.,2014).Forexample,lowdosebacitracinsignif- (Redondo et al., 2014). Lin details that the effective of antibi- icantly enhances biofilm formation whereas low dose penicillin oticsasgrowthpromotersislinkedtodecreasedactivitiesofbile reducesbiofilm.Thisworkunderscoreshowthereareuntoward salt hydrolase, which thus makes targeting this enzyme directly effects that are not predictable when antimicrobials are admin- a promising method for removing antibiotics for use as growth istered at low concentrations. Providing a view on specific host enhancers(Lin,2014). www.frontiersin.org September2014|Volume5|Article478|5 Nosanchuketal. Broadimpactoflow-doseantibiotics You and Silbergeld critically discuss the effects of Corno,G.,Coci,M.,etal.(2014).Antibioticspromoteaggregationwithinaquatic antimicrobials as drivers of resistome expansion (You and bacterialcommunities.Front.Microbiol.5:297.doi:10.3389/fmicb.2014.00297 Silbergeld,2014),amajorsecondaryeffectduetoenvironmental Diarra, M. S., and Malouin, F. (2014). Antibiotics in Canadian poul- try productions and anticipated alternatives. Front. Microbiol. 5:282. doi: pollution.Theeffectsofantibioticspermeatingourenvironment 10.3389/fmicb.2014.00282 are highlighted by Conro and colleagues who present their Hao,H.,Cheng,G.,etal.(2014).Benefitsandrisksofantimicrobialuseinfood- findingsthatthepresenceofantibioticsinaquaticenvironments producinganimals.Front.Microbiol.5:288.doi:10.3389/fmicb.2014.00288 can induce co-aggregation of bacterial species as an effective Imperi, F., Leoni, L., et al. (2014). Antivirulence activity of azithromycin in mechanism to combat the effects of the antimicrobials (Corno Pseudomonas aeruginosa. Front. Microbiol. 5:178. doi: 10.3389/fmicb.2014. 00178 et al., 2014), which can lead to extensive resistance through the Lin,J.(2014).Antibioticgrowthpromotersenhanceanimalproductionbytarget- transferofresistancegenesamongtheseaggregatedbacteria.Itis ingintestinalbilesalthydrolaseanditsproducers.Front.Microbiol.5:33.doi: asmallleapforthesemicrobestothenimpacthumansandother 10.3389/fmicb.2014.00033 organisms.Aminovprovidestheexampleoftherampantuseof Looft, T., Allen, H. K., et al. (2014). Carbadox has both temporary and lasting effects on the swine gut microbiota. Front. Microbiol. 5:276. doi: tetracyclinesfornon-medicalpurposesasdrivingthepenetration 10.3389/fmicb.2014.00276 of tet(X) into pathogenic microbial communities (Aminov, Mihu, M.R.,Pattabhi, R., et al. (2014).Theimpact ofantifungals ontoll-like 2013b).Chowdhuryandcolleagueseloquentlydiscusstheimport receptors.Front.Microbiol.5:99.doi:10.3389/fmicb.2014.00099 ofsurveillancestrategiesforcriticallyelucidatingtheemergence Morita, Y., Tomida, J., et al. (2014). Responses of Pseudomonas aeruginosa to ofdrugresistantpathogensinthecontextoflow-doseantibiotic antimicrobials.Front.Microbiol.4:422.doi:10.3389/fmicb.2013.00422 Redondo, L. M., Chacana, P. A., et al. (2014). Perspectives in the use of tan- useinanimalhusbandry(RoyChowdhuryetal.,2014). ninsasalternativetoantimicrobialgrowthpromoterfactorsinpoultry.Front. In summary, the articles within this Research Topic serve as Microbiol.5:118.doi:10.3389/fmicb.2014.00118 a “call to arms” for scientists, policy makers and the public to Roy Chowdhury, P., McKinnon, J., et al. (2014). Genomic interplay in bac- be increasingly vigilant about the use of antimicrobials, partic- terial communities: implications for growth promoting practices in animal ularlyinlow-doseorwheretheycanbecomewidespreadinthe husbandry.Front.Microbiol.5:394.doi:10.3389/fmicb.2014.00394 Sorensen,A.C.,Lawrence,R.S.,etal.(2014).Interplaybetweenpolicyandscience environment,inordertomaintainourcapacitytoeffectivelycare regardinglow-doseantimicrobialuseinlivestock.Front.Microbiol.5:86.doi: forindividualswithinfectiousdiseases.Thearticlesalsoprovide 10.3389/fmicb.2014.00086 newconceptsforapproachesforthedevelopmentofantimicro- You,Y.,andSilbergeld,E.K.(2014).Learningfromagriculture:understanding bialsaswellasfornovelgrowthenhancersfortheuseinanimal low-dose antimicrobials as drivers of resistome expansion. Front. Microbiol. 5:284.doi:10.3389/fmicb.2014.00284 husbandry. ConflictofInterestStatement:Theauthorsdeclarethattheresearchwascon- REFERENCES ductedintheabsenceofanycommercialorfinancialrelationshipsthatcouldbe Aminov, R. I. (2013a). Biotic acts of antibiotics. Front. Microbiol. 4:241. doi: construedasapotentialconflictofinterest. 10.3389/fmicb.2013.00241 Aminov,R.I.(2013b).Evolutioninaction:disseminationoftet(X)intopathogenic Received:12August2014;accepted:25August2014;publishedonline:10September microbiota.Front.Microbiol.4:192.doi:10.3389/fmicb.2013.00192 2014. Charlebois,A.,Jacques,M.,andArchambault,M.(2014).Biofilmformationof Citation:NosanchukJD,LinJ,HunterRPandAminovRI(2014)Low-doseantibi- Clostridium perfringens and its exposure to low-dose antimicrobials. Front. otics:currentstatusandoutlookforthefuture.Front.Microbiol.5:478.doi:10.3389/ Microbiol.5:183.doi:10.3389/fmicb.2014.00183 fmicb.2014.00478 Chattopadhyay, M. K. (2014). Use of antibiotics as feed additives: a ThisarticlewassubmittedtoAntimicrobials,ResistanceandChemotherapy,asection burning question. Front. Microbiol. 5:334. doi: 10.3389/fmicb.2014. ofthejournalFrontiersinMicrobiology. 00334 Copyright©2014Nosanchuk,Lin,HunterandAminov.Thisisanopen-accessarti- Cheng, G., Hao, H., et al. (2014). Antibiotic alternatives: the substitu- cledistributedunderthetermsoftheCreativeCommonsAttributionLicense(CCBY). tion of antibiotics in animal husbandry? Front. Microbiol. 5:217. doi: The use, distribution or reproduction in other forums is permitted, provided the 10.3389/fmicb.2014.00217 originalauthor(s)orlicensorarecreditedandthattheoriginalpublicationinthis Clark,K.B.(2013).BioticactivityofCa2+-modulatingnontraditionalantimicro- journaliscited,inaccordancewithacceptedacademicpractice.Nouse,distributionor bialand-viralagents.Front.Microbiol.4:381.doi:10.3389/fmicb.2013.00381 reproductionispermittedwhichdoesnotcomplywiththeseterms. FrontiersinMicrobiology|Antimicrobials,ResistanceandChemotherapy September2014|Volume5|Article478|6 REVIEWARTICLE published:19August2013 doi:10.3389/fmicb.2013.00241 Biotic acts of antibiotics RustamI.Aminov* FacultyofMedicalSciences,UniversityoftheWestIndies,Kingston,Jamaica Editedby: Biological functions of antibiotics are not limited to killing. The most likely function of JunLin,TheUniversityofTennessee, antibiotics in natural microbial ecosystems is signaling. Does this signaling function of USA antibioticsalsoextendtotheeukaryotic–inparticularmammalian–cells?Inthisreview, Reviewedby: the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, JoseL.Martinez,CentroNacionalde andβ-lactams)willbebrieflydiscussed.Antibioticscanbeeffectiveintreatmentofabroad Biotecnología,Spain RafaelCanton,HospitalUniversitario spectrum of diseases and pathological conditions other than those of infectious etiology RamonyCajal,Spain and,inthiscapacity,mayfindwidespreadapplicationsbeyondtheintendedantimicrobial *Correspondence: use.Thisuse,however,shouldnotcompromisetheprimaryfunctionantibioticsareused RustamI.Aminov,FacultyofMedical for.Thebiologicalbackgroundforthisinter-kingdomsignalingisalsodiscussed. Sciences,UniversityoftheWest Indies,TeachingandResearch Keywords:tetracyclines,macrolides,β-lactam,inflammation,respiratory,cardiovascular,neuroprotection,cancer Complex,BlockA,RoomA206,Mona Campus,Kingston7,Jamaica e-mail:rustam.aminov@uwimona. edu.jm INTRODUCTION of their activities, including the direct interaction of antibiotics We are all familiar with the use of antibiotics for treatment of withthehostcellsaswellasindirect,throughthemodulationof infectiousdiseases.Butantibioticsdonotonlykillbacteria,their microbiotaand, correspondingly, microbialmetabolites, macro- original role possibly involved signaling functions (Davies etal., molecules,andotherbiologicallyactivecomponentsofmicrobiota 2006; Linaresetal.,2006;Yimetal.,2006,2007; Martínez,2008; thataffectthehost.Andfinally,itisintriguingtorecognizehow Aminov,2009;Romeroetal.,2011).Thesefunctions,usuallyper- manymoleculartargetsforantibioticsareinthehumanbody.Isit formedatlowerconcentrations,aredifferentfromthoseleadingto bychancethattheyhavesuchpleiotropicpropertiesthatareaffect- celldeath,andtheyarerealizedthroughdifferentsetsofmolecular ingalmosteveryorganorsysteminthehumanbody?Onlythree targetsinthecell.Whilemanyaspectsofthiscommunicationin classesof antibioticsarecoveredinthisreviewbecauseof space themicrobialworldremainelusive,thereisalargebodyofinfor- restraints.Thesearethemacrolides,tetracyclines,andβ-lactams. mationregardingthesignalingeffectsoflow-doseantibioticson Forthesamereason,onlyfewmostimportantexamplesforeach humansandanimalsbeyondtheintendedantimicrobialactivities. antibioticclassandforeachgroupofdiseasesaregiven.Theseare Thus the intention of this article is to undertake an interdisci- followedbyadiscussionofvariousimplicationsoftheeffectsand plinarycoverageof andfamiliarizebiologistswiththisaspectof consequencesofthenon-antimicrobialantibioticuse. non-antimicrobialantibioticuseinclinicalresearchandpractice. Theresultscoveredinthisreviewhavebeencollectedinvarious MACROLIDES animal models, tissue cultures, and pre-clinical and clinical tri- There are many examples of antibiotic signaling effects on the als,withlittleornoinvolvementofmicrobiology,and,therefore, host beyond the intended antimicrobial activity. The use of mighthaveescapedtheattentionofmicrobiologists.Ibelievethis macrolides for treatment of non-infectious diseases has the ear- interdisciplinarycoverageishighlyimportanttoclosethegapin liest history among other antibiotics. A considerable amount of non-antimicrobialuseofantimicrobialsforanumberofreasons. informationregardingthetherapeuticpotentialofmacrolidesfor Firstofall,itisthespecificsofthistypeoftherapy,withtheuse non-antimicrobialusehasbeencollectedbeginningfromthelate of low-dose antibiotics for very extended periods of time mea- 1980s. Since then, a great number of animal experiments have suredinweeks,months,andevenyears.Second,whileinclinical beenperformed,manyrepresentativesof thisclassof antibiotics microbiologyagreatdealofattentionispaidtotheappearanceof havegonethroughclinicaltrials, andanumberof drugsinthis antibioticresistanceasasideeffectofantibiotictherapy,thisaspect grouphavebeenapprovedandarecurrentlycommonlyusedin hashadarelativelylowpriorityandhasbeenlargelyoverlookedin clinicalpracticefornon-antimicrobialpurposes. thelow-doselong-termantibiotictreatmenttrials.Anotheraspect Theuseofmacrolideshasbeenespeciallysuccessfulintheman- thatmayneedmorecarefulconsiderationinthistypeoftherapy agementofvariouschronicrespiratorydiseasesnotonlyintherole istheroleofcommensalmicrobiota,whichisalsoanimportant of antimicrobial agents but also due to their anti-inflammatory playerinhumanmetabolismandphysiology.Antibioticsactnot andpro-kineticproperties.Thepositiveeffectoflong-termlow- onlyonthetargetsinthehumanbodybutalsoonthemicrobiota, doseadministrationoferythromycintopatientswithdiffusepan- whichistheintegralpartof humanmetabolismandphysiology. bronchiolitiswasdemonstratedbyJapaneseresearchersmorethan And as we know, the role of commensal microbiota in human twodecadesago,thussuggestingotherthanantimicrobialnature healthanddiseaseisimmense,affectingalmosteveryaspectofit. of erythromycin action (Kudoh etal., 1987; Nagai etal., 1991). Thus the antibiotic effects have to be evaluated from both sides From this point, the use of macrolides for non-antimicrobial www.frontiersin.org August2013|Volume4|Article241|7 “fmicb-04-00241” — 2013/8/16 — 21:17 — page 1 — #1 Aminov Bioticactsofantibiotics purposeshasbecomeoneofthemainstreamchoicesfortreatment The positive effect of clarithromycin in cardiovascular diseases ofchronicrespiratorydiseases. maybeduetothealterationofinflammatoryfactorsandmatrix In cystic fibrosis (CF), the main bacterium associated with metalloproteinases(MMPs).MMPsasapartoftheextracellular the pulmonary disease is Pseudomonas aeruginosa, which pro- matrixparticipateinanumberofnormalphysiologicalprocesses, ducesbiofilmsresistanttoantibiotictreatmentwithintheairways which contribute to tissue structure, function, and remodeling, (Singh etal.,2000). AlthoughP.aeruginosa isnaturallyresistant includingthemyocardium(Spinaleetal.,2013).Boththeexpres- tomacrolides,theseantibiotics,evenatsubinhibitoryconcentra- sionandactivityof MMPsareregulatedbythetissueinhibitors tions,cansuppressquorumsensingnecessaryforbiofilmforma- of matrix metalloproteinases (TIMPs), and the MMPs/TIMPs tion (Tateda etal., 2007). This mechanism possibly contributes balanceiscrucialforthenormalmaintenanceofmyocardialinter- to the heightened sensitivity of non-susceptible P. aeruginosa stitialhomeostasis. Misbalanceandtheresultinginvolvementof toward a variety of anti-pseudomonal agents in biofilms when MMPs in disease, however, have been shown for a number of exposedtomacrolidesatsubinhibitoryconcentrations(Lutzetal., pathologiesspanningfromcancertocardiovasculardiseasesand 2012). In addition, low-dose macrolides display immunomod- toneurodegeneration(Sbardellaetal.,2012).Theprotectiveeffect ulatory properties influencing cytokine production and altering ofclarithromycininthecaseofautoimmunemyocarditisappears polymorphonuclearcellfunctions(Schultz,2004).Thisprevents tobeimplementedthroughtheinhibitionoftheMMP-9activity excessiveuncontrolledinflammationandassociatedtissuedam- (Hishikarietal.,2010).Inthelongrun,however,ashort-termclar- age.Anotherbenefitofthemacrolideuseinthemanagementof ithromycinadministrationinpatientswithcoronaryheartdisease CFisthereducedchronicairwayhypersecretion(Tamaokietal., for clearance of suspected infections results in increased risk of 1995). mortality(Gluudetal.,2008). Treatment of other respiratory diseases such as asthma may Immunosuppressiveactivitiesofmacrolideshavebeenknown benefit from the dual action of macrolides because asthma is a foralmostfourdecadesnow.Thefirstmacrolidewiththisactiv- result of interaction of genetic and environmental factors. The ity,rapamycin(alsocalledsirolimus),wasdiscoveredbyBrazilian presence of Mycoplasma pneumoniae and Chlamydophila pneu- researchersduringascreeningprogramforantifungalcompounds moniae in asthmatics best identifies the macrolide responsive produced by soil bacteria (Vézina etal.,1975). But its use as an phenotype because of the antimicrobial and anti-inflammatory antifungalantibiotichasbeenabandonedduetopotentimmuno- properties of macrolides covering the infection and genetic suppressive and antiproliferative activities. Its antiproliferative predispositioncontinuum(Goodetal.,2012). actionisrealizedthroughtheformationofanactivecomplexwith Chronicobstructivepulmonarydisease(COPD)remainsone its cytosolic receptor protein, FKBP12, and targeting of a puta- of theimportantcausesof morbidity,mortality,andhealth-care tivelipidkinasetermedtargetof rapamycin(TOR;Brownetal., costsworldwide(ManninoandBuist,2007). Althoughsmoking 1994; Sabers etal., 1995; Wiederrecht etal., 1995). The loss of is the most important risk factor for the disease, it also has a TORfunctionleadstotheinhibitionof G1-toS-phaseprogres- substantialgeneticcomponent(Wainetal.,2012).Pathogenesisin sion in various sensitive cells. The immunosuppressive activity COPDislargelydrivenbydysregulatedresponsesoftheinnateand of rapamycinisalsorealizedviathesameproteinkinaseinhibi- adaptiveimmunesystemstotheenvironmentalcuesleadingtoan tion pathway affecting cell-cycle proliferation of lymphoid cells exaggeratedinflammatoryresponse,whichresultsinpermanent (Abraham,1998). inflammation, tissue damage, and lung function decline (Hol- The TOR complexes regulate cell growth and metabolism in lowayandDonnelly,2013).Awell-designed,randomized,1-year response to environmental and intracellular cues and are com- trialoferythromycin,atadoseof250mgtwicedaily,hasfound prised of two distinct multiprotein complexes: TOR complex 1 asignificantreductioninCOPDexacerbationscomparedtothe (TORC1), which is sensitive to rapamycin, and TORC2, which placebogroup(Seemungaletal.,2008).Long-termadministration is not (Wullschleger etal., 2006). Dysregulation of these com- ofazithromycinbyoutpatientswithsevereCOPDhasappearedto plexes is associated with various pathologies, including cancer, besafeandeffective,withreducedexacerbations,hospitalizations, cardiovasculardiseases,autoimmunity,metabolicdisorders,and andimprovedqualityoflife(Blasietal.,2010).Anothertrialwith neurodegenerative diseases. Thus rapamycin and its derivatives a daily azithromycin for 1 year for prevention of exacerbations canbeusedfortreatmentofavarietyofdiseases(Cruzado,2008). ofCOPDhasdemonstrateddecreasedfrequencyofexacerbations Itisalsopotentiallyusefulfortreatmentofsubstanceabusecon- andimprovedqualityof lifebuthascausedhearingdecrements ditions, alcohol abuse in particular, since inhibition of TORC1 in a small percentage of subjects (Albert etal., 2011). A recent by rapamycin disrupts alcohol-associated memory reconsolida- reviewofcontrolledclinicalstudiesfocusingonthepreventionof tion,leadingtoalong-lastingsuppressionofrelapse(Baraketal., COPDexacerbationswithlong-termazithromycin,erythromycin, 2013).Currentlyitisapprovedforpreventionoftransplantrejec- orclarithromycintreatmentsuggeststhatitiseffective,safe,and tion,anditslatestderivative,everolimus,iswidelyusedtoprevent cost-efficient(Simoensetal.,2013).Otherchronicrespiratorydis- therejectionofheart,lung,kidney,orliverallografts(Gurk-Turner easesmayalsobetreatedbymacrolides,butbetterdesignedtrials etal., 2012). Since TOR complexes are evolutionary conserved arenecessarytoconfirmtheirefficacy(SureshBabuetal.,2013). and involved in very fundamental biological processes in the Novel effects of macrolides on cardiovascular diseases have cell, pharmacologicalinhibitionof TORsignalingbyrapamycin been discovered recently. In animal models, clarithromycin has increases the lifespan of yeasts and higher eukaryotes (Powers suppressedthedevelopmentofmyocarditis,cardiacrejection,and etal., 2006). The use of rapamycin in humans as an anti-aging myocardial ischemia (Nakajima etal.,2010; Suzuki etal.,2012). agentisuncertainbecauseofsideeffects;thisusewillrequirethe FrontiersinMicrobiology|Antimicrobials,ResistanceandChemotherapy August2013|Volume4|Article241|8 “fmicb-04-00241” — 2013/8/16 — 21:17 — page 2 — #2

Description:
The biological background for this inter-kingdom signaling is also discussed. Keywords: .. In a subset of patients the use of tacrolimus for the management domonas aeruginosa through interaction with the outer membrane. Antimi- .. BCADTEF-ugd operon, otherwise known as pmrHFIJKLM-ugd.
See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.