Biotechnological applications of quorum quenching enzymes
Authors: Laure Plener
Janek Bzdrenga
Pauline Jacquet
David Daudé
Mikael Elias
Benjamin Rémy
Eric Chabrière
Journal: Chemico-Biological Interactions (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Biofilm; Enzyme; Lactonase; Quorum quenching; Quorum sensing
Affiliations: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France., Gene&GreenTK, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 5, France., Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France; Gene&GreenTK, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 5, France., University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics & Biotechnology Institute, St. Paul, MN 55108, USA., Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France. Electronic address: .

Abstract:  Numerous bacteria use quorum sensing (QS) to synchronize their behavior and monitor their population density. They use signaling molecules known as autoinducers (AI's) that are synthesized and secreted into their local environment to regulate QS-dependent gene expression. Among QS-regulated pathways, biofilm formation and virulence factor secretion are particularly problematic as they are involved in surface-attachment, antimicrobial agent resistance, toxicity, and pathogenicity. Targeting QS represents a promising strategy to inhibit undesirable bacterial traits. This strategy, referred to as quorum quenching (QQ), includes QS-inhibitors and QQ enzymes. These approaches are appealing because they do not directly challenge bacterial survival, and consequently selection pressure may be low, yielding a lower occurrence of resistance. QQ enzymes are particularly promising because they act extracellularly to degrade AI's and can be used in catalytic quantities. This review draws an overview of QQ enzyme related applications, covering several economically important fields such as agriculture, aquaculture, biofouling and health issues. Finally, the possibility of resistance mechanism occurrence to QQ strategies is discussed. 

Retracted: No

PubPeer comments:
 The abstract of this paper states:  Numerous bacteria use quorum sensing (QS) to synchronize their behavior and monitor their population density. They use signaling molecules known as autoinducers (AI s) that are synthesized and secreted into their local environment to regulate QS-dependent gene expression. Among QS- regulated pathways, biofilm formation and virulence factor secretion are particularly problematic as they are involved in surface-attachment, antimicrobial agent resistance, toxicity, and pathogenicity. Targeting QS represents a promising strategy to inhibit undesirable bacterial traits. This strategy, referred to as quorum quenching (QQ), includes QS-inhibitors and QQ enzymes. These approaches are appealing because they do not directly challenge bacterial survival, and consequently selection pressure may be low, yielding a lower occurrence of resistance. QQ enzymes are particularly promising because they act extracellularly to degrade AI s and can be used in catalytic quantities. This review draws an overview of QQ enzyme related applications, covering several economically important fields such as agriculture, aquaculture, biofouling and health issues. Finally, the possibility of resistance mechanism occurrence to QQ strategies is discussed. I could not find any conflict of interest statement. However, the two last authors did not disclose that they are founders of a biotech company called  Gene GreenTK , which was founded in 2013, thus pre-dating the submission of this paper. Three authors list Gene GreenTK as their affiliations, but there is no statement that the last two authors are founders of the company, and thus might have a financial interest in publishing about these enzymes. The company s expertise appears very relevant to the enzymes described in the paper. Some quotes from their website https: www.gene-greentk.com (archived: https: archive.is 6Gr1R) : *  The work of G G is dedicated to the development and engineering of enzymes isolated from microorganisms living in extreme environments. *  We develop enzymes that ally both perfomance [sic] and stability. Coming straight from extreme environments and produced by hyperthermophilic microorganisms. *  Bacteria use chemical signals to communicate and coordinate behaviors including virulence and biofilm formation. Our technology interrupts bacterial communication by degrading signal molecules thereby preventing bacteria from forming biofilms and to start a virulence program. *  Anti-virulence and anti-biofilm for the development of novel medical devices, anti-fouling paintings or coatings and biobased materials ![file] Based on recent social media activities (e.g. https: archive.is FI9sH - https: archive.is RWmwF - https: archive.is 0hECd), one of the authors appears to be very interested in pointing out other authors conflicts of interest. Could he or other authors please comment on this perceived conflict? , 
 Dear Dr. Bik, Your harassment on pubpeer on our research articles, as evidenced by your last statement u201cBased on recent social media activities, author EC appears to be very interested in pointing out other authors conflict of interest. Could he or other authors please comment on this perceived conflict?u201d does not honor you. The presence of GGTK authors (3 out of 7) is a clear indication of a potential conflict of interest with this paper and the company. However, a statement would presumably exist if it was required. Authors will investigate this matter. , 
 Dear Dr. Bik, After verification, your allegation: u201c (u2026) but there is no statement that the last two authors (u2026) might have a financial interest in publishing about these enzymes.u201d Is false. ![file] COI were declared for each author at the time of the publication, to the publisher. After confirming directly with the journal, they have been available online on the very journal article page since the day of publication. Your comment could therefore be construed as defamation. , 
 Dear Dr. Elias, In the version of the paper that I have, I could not find such statements about Conflicts of Interest. It is great that you filled out the appropriate form, but I could not find such a statement in my version of the paper. In most papers that I am familiar with, such conflicts of interest are declared in the paper itself, and I could not find them there. Maybe they are listed on the paper s landing page, but I do not have access to them. Also, under section 2 of the form you posted above, you actually stated that there were NO relevant conflicts of interest for the work under consideration. Can you please explain how that fits your statement that you declared the CoI? You only checked the box about CoI under section 3, which refers to financial activities **outside the submitted work**. Should the box under section 2 not also have been checked? I hope we can continue our conversation in a professional manner. , 
 Dr. Bik, It is unacceptable that you make false statements. You explicitly claimed above that there was no COI statements, and there are. The COI statement is filed properly, for all authors, and according to journal policy. The complete form cannot be attached to pubpeer due to format issue (pdf not accepted). ![file] It is not acceptable that you do not properly check, and are satisfied with  the version (you) have . It is however the method you have used to  comment my papers. I have no intention to dialogue with my harasser. , 
 #5 You may post those files to an external file repository (like Google Docs) and post a link to them here. As far as harassing, I am sympathetic to you being sensitive about critical questions, but Dr. Bik did not accuse you of anything - she asked for clarification, which you seem to be able to provide - and by using a public forum like PubPeer, many readers can be similarly informed at the same time. Thank you for responding and I look forward to seeing the documentation. , 
 Dr Dr. Bik and others, I am pasting below a link for the COI disclosures package that is available on the article page. Please let me know if there is any issue with the link. Best, Mikael Elias https: drive.google.com file d 1wiuxpQ2eEDRBB6Cu-UCWjwdGd0Awa1tf view?usp=sharing , 
 #7 Thank you, that seems to work for me. , 
 Thank you, Dr. Elias, for posting these documents. I am so glad you could take away the concerns I had about potential conflicts of interest with respect to this paper. Thank you for your willingness to share these. ,