Insights in the Antimicrobial Potential of the Natural Nisin Variant Nisin H

Lantibiotics are a growing class of antimicrobial peptides, which possess antimicrobial activity against mainly Gram-positive bacteria including the highly resistant strains such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci. In the last decades numerous lantibiotics were discovered in natural habitats or designed with bioengineering tools. In this study, we present an insight in the antimicrobial potential of the natural occurring lantibiotic nisin H from Streptococcus hyointestinalis as well as the variant nisin H F1I. We determined the yield of the heterologously expressed peptide and quantified the cleavage efficiency employing the nisin protease NisP. Furthermore, we analyzed the effect on the modification via mass spectrometry analysis. With standardized growth inhibition assays we benchmarked the activity of pure nisin H and the variant nisin H F1I, and their influence on the activity of the nisin immunity proteins NisI and NisFEG from Lactococcus lactis and the nisin resistance proteins SaNSR and SaNsrFP from Streptococcus agalactiae COH1. We further checked the antibacterial activity against clinical isolates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis via microdilution method. In summary, nisin H and the nisin H F1I variant possessed better antimicrobial potency than the natural nisin A.

[1]  substrate specificity , 2020, Catalysis from A to Z.

[2]  R. P. Ross,et al.  Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota , 2019, Journal of bacteriology.

[3]  S. Smits,et al.  Influence of nisin hinge-region variants on lantibiotic immunity and resistance proteins. , 2019, Bioorganic & medicinal chemistry.

[4]  S. Smits,et al.  Bypassing lantibiotic resistance by an effective nisin derivative. , 2019, Bioorganic & medicinal chemistry.

[5]  Simon C. Potter,et al.  The EMBL-EBI search and sequence analysis tools APIs in 2019 , 2019, Nucleic Acids Res..

[6]  S. Smits,et al.  Systematic characterization of position one variants within the lantibiotic nisin , 2019, Scientific Reports.

[7]  R. P. Ross,et al.  Human skin microbiota is a rich source of bacteriocin-producing staphylococci that kill human pathogens , 2018, FEMS microbiology ecology.

[8]  C. Hill,et al.  Bioengineering nisin to overcome the nisin resistance protein , 2018, Molecular microbiology.

[9]  S. Sandiford Current developments in lantibiotic discovery for treating Clostridium difficile infection , 2018, Expert opinion on drug discovery.

[10]  E. Breukink,et al.  High-resolution NMR studies of antibiotics in cellular membranes , 2018, Nature Communications.

[11]  Oscar P. Kuipers,et al.  BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins , 2018, Nucleic Acids Res..

[12]  A. Løbner-Olesen,et al.  Expanding the potential of NAI-107 for treating serious ESKAPE pathogens: synergistic combinations against Gram-negatives and bactericidal activity against non-dividing cells , 2017, The Journal of antimicrobial chemotherapy.

[13]  H. Flint,et al.  Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract. , 2017, Microbiology.

[14]  S. Smits,et al.  The N-terminal Region of Nisin Is Important for the BceAB-Type ABC Transporter NsrFP from Streptococcus agalactiae COH1 , 2017, Front. Microbiol..

[15]  S. Smits,et al.  Substrate Specificity of the Secreted Nisin Leader Peptidase NisP. , 2017, Biochemistry.

[16]  S. Nair,et al.  Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes , 2017, Chemical reviews.

[17]  P. Neubauer,et al.  Pharmacological and pharmacokinetic properties of lanthipeptides undergoing clinical studies , 2017, Biotechnology Letters.

[18]  E. Breukink,et al.  Hit 'em where it hurts: The growing and structurally diverse family of peptides that target lipid-II. , 2016, Biochimica et biophysica acta.

[19]  S. Smits,et al.  Protein Defense Systems against the Lantibiotic Nisin: Function of the Immunity Protein NisI and the Resistance Protein NSR , 2016, Front. Microbiol..

[20]  Holger Gohlke,et al.  Structural basis of lantibiotic recognition by the nisin resistance protein from Streptococcus agalactiae , 2016, Scientific Reports.

[21]  Michael J E Sternberg,et al.  The Phyre2 web portal for protein modeling, prediction and analysis , 2015, Nature Protocols.

[22]  R. P. Ross,et al.  Nisin H Is a New Nisin Variant Produced by the Gut-Derived Strain Streptococcus hyointestinalis DPC6484 , 2015, Applied and Environmental Microbiology.

[23]  O. Kuipers,et al.  The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity , 2015, Front. Microbiol..

[24]  S. Nair,et al.  Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB , 2014, Nature.

[25]  S. Smits,et al.  The C-terminus of nisin is important for the ABC transporter NisFEG to confer immunity in Lactococcus lactis , 2014, MicrobiologyOpen.

[26]  S. Smits,et al.  Lantibiotic Immunity: Inhibition of Nisin Mediated Pore Formation by NisI , 2014, PloS one.

[27]  Chengping Lu,et al.  Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island. , 2014, Gene.

[28]  S. Smits,et al.  NSR from Streptococcus agalactiae confers resistance against nisin and is encoded by a conserved nsr operon , 2013, Biological chemistry.

[29]  O. Kuipers,et al.  NisC binds the FxLx motif of the nisin leader peptide. , 2013, Biochemistry.

[30]  X. Yang,et al.  Ribosomally synthesized and post-translationally modified peptide natural products: new insights into the role of leader and core peptides during biosynthesis. , 2013, Chemistry.

[31]  Yi-Zun Yu,et al.  Evolution of lanthipeptide synthetases , 2012, Proceedings of the National Academy of Sciences.

[32]  M. Dawson,et al.  New horizons for host defense peptides and lantibiotics. , 2012, Current opinion in pharmacology.

[33]  S. Donadio,et al.  Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens , 2011, Antimicrobial Agents and Chemotherapy.

[34]  R. Rink,et al.  Requirements of the Engineered Leader Peptide of Nisin for Inducing Modification, Export, and Cleavage , 2010, Applied and Environmental Microbiology.

[35]  Jin Zhong,et al.  [Improving heat and pH stability of nisin by site-directed mutagenesis]. , 2010, Wei sheng wu xue bao = Acta microbiologica Sinica.

[36]  O. Kuipers,et al.  Directionality and Coordination of Dehydration and Ring Formation during Biosynthesis of the Lantibiotic Nisin , 2009, The Journal of Biological Chemistry.

[37]  L. Dicks,et al.  Characterization of the Structural Gene Encoding Nisin F, a New Lantibiotic Produced by a Lactococcus lactis subsp. lactis Isolate from Freshwater Catfish (Clarias gariepinus) , 2007, Applied and Environmental Microbiology.

[38]  W. A. van der Donk,et al.  Identification of Essential Catalytic Residues of the Cyclase NisC Involved in the Biosynthesis of Nisin* , 2007, Journal of Biological Chemistry.

[39]  Xuxia Zhou,et al.  The nisin-controlled gene expression system: construction, application and improvements. , 2006, Biotechnology advances.

[40]  S. Nair,et al.  Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis , 2006, Science.

[41]  J. Tagg,et al.  Molecular and Genetic Characterization of a Novel Nisin Variant Produced by Streptococcus uberis , 2006, Applied and Environmental Microbiology.

[42]  Michiel Kleerebezem,et al.  10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis , 2005, Applied Microbiology and Biotechnology.

[43]  O. Kuipers,et al.  University of Groningen Lantibiotic structures as guidelines for the design of peptides that can be modified by lantibiotic enzymes Rink, , 2018 .

[44]  R. Kaptein,et al.  The nisin–lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics , 2004, Nature Structural &Molecular Biology.

[45]  B. de Kruijff,et al.  Assembly and stability of nisin-lipid II pores. , 2004, Biochemistry.

[46]  R. Benz,et al.  Lipid II-Mediated Pore Formation by the Peptide Antibiotic Nisin: a Black Lipid Membrane Study , 2004, Journal of bacteriology.

[47]  W. A. van der Donk,et al.  SpaC and NisC, the cyclases involved in subtilin and nisin biosynthesis, are zinc proteins. , 2003, Biochemistry.

[48]  J. Nakayama,et al.  Identification of the Lantibiotic Nisin Q, a New Natural Nisin Variant Produced by Lactococcus lactis 61-14 Isolated from a River in Japan , 2003, Bioscience, biotechnology, and biochemistry.

[49]  P. Saris,et al.  NisB is required for the dehydration and NisC for the lanthionine formation in the post-translational modification of nisin. , 2002, Microbiology.

[50]  B. de Kruijff,et al.  Lipid II induces a transmembrane orientation of the pore-forming peptide lantibiotic nisin. , 2002, Biochemistry.

[51]  Oscar P. Kuipers,et al.  Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity* , 2001, The Journal of Biological Chemistry.

[52]  G. LaPointe,et al.  MICs of Mutacin B-Ny266, Nisin A, Vancomycin, and Oxacillin against Bacterial Pathogens , 2000, Antimicrobial Agents and Chemotherapy.

[53]  M. Gasson,et al.  Post-translational modification of nisin. The involvement of NisB in the dehydration process. , 1999, European journal of biochemistry.

[54]  M. Kleerebezem,et al.  Use of the Lactococcal nisA Promoter To Regulate Gene Expression in Gram-Positive Bacteria: Comparison of Induction Level and Promoter Strength , 1998, Applied and Environmental Microbiology.

[55]  R. Siezen,et al.  The orientation of nisin in membranes. , 1998, Biochemistry.

[56]  J. Watson,et al.  Optimization of the cleavage reaction for cyanylated cysteinyl proteins for efficient and simplified mass mapping. , 1998, Analytical biochemistry.

[57]  M. Poot,et al.  Bacterial viability and antibiotic susceptibility testing with SYTOX green nucleic acid stain , 1997, Applied and environmental microbiology.

[58]  M. Kleerebezem,et al.  Controlled overproduction of proteins by lactic acid bacteria. , 1997, Trends in biotechnology.

[59]  M. Gasson,et al.  Structure‐activity relationships in the peptide antibiotic nisin: antibacterial activity of fragments of nisin , 1996, FEBS letters.

[60]  R. Evans,et al.  Applications of the bacteriocin, nisin , 1996, Antonie van Leeuwenhoek.

[61]  W. D. de Vos,et al.  Improvement of solubility and stability of the antimicrobial peptide nisin by protein engineering , 1995, Applied and environmental microbiology.

[62]  Peter Ruhdal Jensen,et al.  Minimal Requirements for Exponential Growth of Lactococcus lactis , 1993, Applied and environmental microbiology.

[63]  T. Klaenhammer,et al.  Genetics of bacteriocins produced by lactic acid bacteria. , 1993, FEMS microbiology reviews.

[64]  W. D. de Vos,et al.  Identification and characterization of the lantibiotic nisin Z, a natural nisin variant. , 1991, European journal of biochemistry.

[65]  I. Nes,et al.  High-Frequency Transformation, by Electroporation, of Lactococcus lactis subsp. cremoris Grown with Glycine in Osmotically Stabilized Media , 1989, Applied and environmental microbiology.

[66]  K. Entian,et al.  Nisin, a peptide antibiotic: cloning and sequencing of the nisA gene and posttranslational processing of its peptide product , 1989, Journal of bacteriology.

[67]  W. Sandine,et al.  Improved Medium for Lactic Streptococci and Their Bacteriophages , 1975, Applied microbiology.

[68]  E. Gross,et al.  The presence of dehydroalanine in the antibiotic nisin and its relationship to activity. , 1967, Journal of the American Chemical Society.

[69]  L. A. Rogers THE INHIBITING EFFECT OF STREPTOCOCCUS LACTIS ON LACTOBACILLUS BULGARICUS , 1928, Journal of bacteriology.

[70]  L. A. Rogers,et al.  LIMITING FACTORS IN THE LACTIC FERMENTATION , 1928, Journal of bacteriology.

[71]  G. Bierbaum,et al.  Lantibiotics: promising candidates for future applications in health care. , 2014, International journal of medical microbiology : IJMM.

[72]  P. G. Arnison,et al.  Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. , 2013, Natural product reports.

[73]  M. Wilcox,et al.  Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection. , 2013, The Journal of antimicrobial chemotherapy.

[74]  M. Stronati,et al.  [Streptococcus agalactiae]. , 2003, La Pediatria medica e chirurgica : Medical and surgical pediatrics.

[75]  H. Sahl,et al.  Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. , 1998, Annual review of microbiology.

[76]  J. Waitz Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically , 1990 .