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Characterization of Milkisin, a Novel Lipopeptide with Antimicrobial Properties Produced by Pseudomonas Sp

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Characterization of Milkisin, a Novel Lipopeptide with Antimicrobial Properties Produced by Pseudomonas Sp Characterization of Milkisin, a Novel Lipopeptide With Antimicrobial Properties Produced By Pseudomonas sp. UCMA 17988 Isolated From Bovine Raw Milk Margot Schlusselhuber, Justine Godard, Muriel Sebban, Benoit Bernay, David Garon, Virginie Seguin, Hassan Oulyadi, Nathalie Desmasures To cite this version: Margot Schlusselhuber, Justine Godard, Muriel Sebban, Benoit Bernay, David Garon, et al.. Charac- terization of Milkisin, a Novel Lipopeptide With Antimicrobial Properties Produced By Pseudomonas sp. UCMA 17988 Isolated From Bovine Raw Milk. Frontiers in Microbiology, Frontiers Media, 2018, 9, pp.1030. 10.3389/fmicb.2018.01030. hal-02176304 HAL Id: hal-02176304 https://hal.archives-ouvertes.fr/hal-02176304 Submitted on 8 Jul 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. fmicb-09-01030 May 24, 2018 Time: 15:50 # 1 ORIGINAL RESEARCH published: 28 May 2018 doi: 10.3389/fmicb.2018.01030 Characterization of Milkisin, a Novel Lipopeptide With Antimicrobial Properties Produced By Pseudomonas sp. UCMA 17988 Isolated From Bovine Raw Milk Margot Schlusselhuber1*, Justine Godard1, Muriel Sebban2, Benoit Bernay3, David Garon1, Virginie Seguin1, Hassan Oulyadi2 and Nathalie Desmasures1 1 UNICAEN, UNIROUEN, ABTE, Normandie Université, Caen, France, 2 UNIROUEN, INSA Rouen, CNRS, COBRA, Normandie Université, Rouen, France, 3 UNICAEN, SF ICORE 4206, Normandie Université, Caen, France Biosurfactants such as lipopeptides are amphiphilic compounds produced by Edited by: microorganisms such as bacteria of the genera of Pseudomonas and Bacillus. Some Santi M. Mandal, of these molecules proved to have interesting antimicrobial, antiviral, insecticide, and/or Indian Institute of Technology tensioactive properties that are potentially useful for the agricultural, chemical, food, and Kharagpur, India pharmaceutical industries. Raw milk provides a physicochemical environment that is Reviewed by: Taoufik Ghrairi, favorable to the multiplication of a broad spectrum of microorganisms. Among them, Tunis El Manar University, Tunisia psychrotrophic bacterial species, especially members of the genus Pseudomonas, are Suresh Korpole, Institute of Microbial predominant and colonize milk during cold storage and/or processing. We isolated the Technology (CSIR), India strain Pseudomonas sp. UCMA 17988 from raw cow milk, with antagonistic activity *Correspondence: against Listeria monocytogenes, Staphylococcus aureus, and Salmonella enterica Margot Schlusselhuber Newport. Antimicrobial molecules involved in the antagonistic activity of this strain [email protected] were characterized. A mass spectrometry analysis highlighted the presence of four Specialty section: lipopeptides isoforms. The major isoform (1409 m/z), composed of 10 carbons in This article was submitted to Antimicrobials, Resistance the lipidic chain, was named milkisin C. The three other isoforms detected at 1381, and Chemotherapy, 1395, and 1423 m/z, that are concomitantly produced, were named milkisin A, B, a section of the journal and D, respectively. The structure of milkisin, as confirmed by nuclear magnetic Frontiers in Microbiology resonance analyses, is closely related to amphisin family. Indeed, the peptidic chain was Received: 26 January 2018 Accepted: 01 May 2018 composed of 11 amino acids, 6 of which are conserved among the family. In conclusion, Published: 28 May 2018 Pseudomonas sp. UCMA 17988 produces new members of the amphisin family which Citation: are responsible for the antagonistic activity of this strain. Schlusselhuber M, Godard J, Sebban M, Bernay B, Garon D, Keywords: antimicrobial activity, Pseudomonas, milkisin, amphisin, lipopeptide Seguin V, Oulyadi H and Desmasures N (2018) Characterization of Milkisin, a Novel INTRODUCTION Lipopeptide With Antimicrobial Properties Produced By Biosurfactants are amphiphilic compounds produced by microorganisms such as bacteria, yeasts, Pseudomonas sp. UCMA 17988 Isolated From Bovine Raw Milk. and some filamentous fungi (Santos et al., 2016). They contain hydrophobic and hydrophilic Front. Microbiol. 9:1030. groups that confer the ability to accumulate between fluid phases, thereby reducing surface and doi: 10.3389/fmicb.2018.01030 interfacial tension at the surface and interfacial regions, respectively (Kapadia and Yagnik, 2013). Frontiers in Microbiology| www.frontiersin.org 1 May 2018| Volume 9| Article 1030 fmicb-09-01030 May 24, 2018 Time: 15:50 # 2 Schlusselhuber et al. Milkisin, New Lipopeptide From Pseudomonas Among these molecules, some of them were shown to lipase, causing triglycerides degradation, pseudomonads may have interesting antimicrobial, antiviral, insecticide, and/or cause spoilage in dairy products (Cousin et al., 2001). Within this tensioactive properties that are potentially useful for the genus, the P. fluorescens group is generally known to frequently agricultural, chemical, food, and pharmaceutical industries (Inès cause spoilage of stored milk (Arslan et al., 2011) and of some and Dhouha, 2015). cheese varieties, although it has also been described on the surface Biosurfactants, such as lipopeptides and glycolipids, are in of unspoiled cheese (Larpin-Laborde et al., 2011; Wolfe et al., most cases low-molecular mass membrane-active compounds 2014). (usually ranging from 500 to 1500 Da) (Janek et al., 2010). They In this work, we aim to describe a novel lipopeptide produced are mainly produced by bacteria of the genera Pseudomonas by an isolated strain from bovine raw milk collected in Normandy and Bacillus with 70 and 90 different lipopeptides produced, (France) and identified as Pseudomonas sp. UCMA 17988. This respectively (Santos et al., 2016; Coutte et al., 2017). Recently, a strain produces a novel antibacterial cyclic lipopeptide along with unique online database dedicated to non-ribosomal peptides has three isoforms supposed to belong to the amphisin family. The been opened (Flissi et al., 2016). 139 lipopeptides produced by structure of the newly discovered biosurfactant, named milkisin, Pseudomonas have been recorded and classified into 15 family isolated by RP-HPLC, was determined by mass spectrometry based on their structures. The better known being amphisin, (MALDI TOF) and nuclear magnetic resonance (NMR). pyoverdine, viscosin, tolaasin, and syringopeptin groups1. Several isoforms can be produced by one single strain which differs either by the length of the fatty acid chain or by MATERIALS AND METHODS the composition of the peptide moiety. In Pseudomonas and Bacillus genera, most lipopeptides are synthesized in a ribosome- Isolation and Antibacterial Activity of independent manner with mega enzymes called non-ribosomal Pseudomonas sp. UCMA 17988 peptide synthetases (NRPSs) (Inès and Dhouha, 2015). Those Raw bulk tank milk samples collected on farm in Normandy synthetases possess a multimodular structure in which each (France) were screened for isolates with antibacterial properties module is involved in the stepwise incorporation of an amino by a double layer agar method. After 10-fold dilution of the acid in the lipopeptide peptide moiety. A typical module can samples, 100 ml of each dilution was spread over the surface of be subdivided into initiation and elongation modules. A typical brain heart infusion (BHI) agar plates supplemented with 0.2% initiation module consists of an adenylation (A) domain, glucose and incubated overnight at 30◦C. After incubation, 8 ml responsible for amino acid selection and activation, a thiolation of BHI soft agar supplemented with 0.2% glucose was mixed with (T or alternatively PCP) domain responsible for thioesterification 1% (vol/vol) fresh inoculum prepared from overnight culture of of the activated amino acid and a condensation (C) domain. bacterial pathogens and overlaid on agar plates containing less The C domain of the first module catalyzes N-acylation of than 100 colonies. The bacterial targets used for the screening the first amino acid, thereby linking the lipid moiety to the process were Listeria monocytogenes WSLC 1685, Staphylococcus oligopeptide. Elongation modules contain A, T, and C domains aureus CIP 53.154, Salmonella enterica serotype Newport CIP in which the C domain is responsible for peptide bond formation 105629, and Escherichia coli O157:H7 stx-C267 (Vernozy-Rozand between two neighboring substrates to elongate the peptide et al., 2000). The plates were then incubated overnight at chain. These catalytic domains generate a linear peptide which 30◦C. Milk isolates with antagonistic activity were detected by is cleaved at the end of the assembly line by a thioesterase (TE observation of a zone of inhibition around the colonies. The domain), which results in the release of a linear product or antagonistic Pseudomonas sp. UCMA 17988, detected by this a cyclic compound via an intramolecular cyclization reaction. method, was picked up with sterile toothpick for purification by Additional domains may include an epimerization domain, isolation using Tryptone Soya Agar – Yeast Extract (TSA-YE) responsible for the conversion of the L- or D-configuration
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