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Khusainov R.,University of Groningen | Moll G.N.,Lanthio Pharma | Kuipers O.P.,University of Groningen | Kuipers O.P.,Kluyver Center for Genomics of Industrial Fermentation
FEBS Open Bio | Year: 2013

Nisin is the most prominent and applied bacteriocin that serves as a model for class I lantibiotics. The nisin leader peptide importantly determines interactions between precursor nisin and its modification enzymes NisB and NisC that mature nisin posttranslationally. NisB dehydrates serines and threonines, while NisC catalyzes the subsequent coupling of the formed dehydroamino acids to form lanthionines. Currently, little is known about how the nisin leader interacts with NisB and even less is known about its interactions with NisC. To investigate the nisin leader peptide requirements for functional interaction with the modification enzymes NisB and NisC, we systematically replaced six regions, of 2-4 amino acids each, with all-alanine regions. By performing NisB and NisC co-purification studies with these mutant leader peptides, we demonstrate that the nisin leader regions STKD(-22-19), FNLD(-18-15) and PR(-2-1) importantly contribute to the interactions of precursor nisin with both NisB and NisC, whereas the nisin leader region LVSV(-14-11) additionally contributes to the interaction of precursor nisin with NisC. •Not all nisin leader regions are crucial for the interactions with modifying enzymes.•The leader region STKD(-22-19) is important for the interactions with NisB and NisC.•The nisin leader region FNLD(-18-15) is important for the interactions with NisB and NisC.•The nisin leader region PR(-2-1) is important for the interactions with NisB and NisC.•The leader region LVSV(-14-11) is additionally important for the interactions with NisC. © 2013 The Authors.

van den Berg S.,Erasmus Medical Center | Bonarius H.P.,IQ Therapeutics | van Kessel K.P.,University Utrecht | Elsinga G.S.,IQ Therapeutics | And 9 more authors.
International journal of medical microbiology : IJMM | Year: 2015

Due to substantial therapy failure and the emergence of antibiotic-resistant Staphylococcus aureus strains, alternatives for antibiotic treatment of S. aureus infections are urgently needed. Passive immunization using S. aureus-specific monoclonal antibodies (mAb) could be such an alternative to prevent and treat severe S. aureus infections. The invariantly expressed immunodominant staphylococcal antigen A (IsaA) is a promising target for passive immunization. Here we report the development of the human anti-IsaA IgG1 mAb 1D9, which was shown to bind to all 26 S. aureus isolates tested. These included both methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively). Immune complexes consisting of IsaA and 1D9 stimulated human as well as murine neutrophils to generate an oxidative burst. In a murine bacteremia model, the prophylactic treatment with a single dose of 5 mg/kg 1D9 improved the survival of mice challenged with S. aureus isolate P (MSSA) significantly, while therapeutic treatment with the same dose did not influence animal survival. Neither prophylactic nor therapeutic treatment with 5 mg/kg 1D9 resulted in improved survival of mice with S. aureus USA300 (MRSA) bacteremia. Importantly, our studies show that healthy S. aureus carriers elicit an immune response which is sufficient to generate protective mAbs against invariant staphylococcal surface antigens. Human mAb 1D9, possibly conjugated to for example another antibody, antibiotics, cytokines or chemokines, may be valuable to fight S. aureus infections in patients. Copyright © 2014 Elsevier GmbH. All rights reserved.

Lanthio Pharma | Entity website

Publications Wagenaar GT, Laghmani EH, Fidder M, Sengers RM, de Visser YP, de Vries L, Rink R, Roks AJ, Folkerts G, Walther FJ, (2012) Agonists of MAS oncogene and angiotensin II type 2 receptors attenuate cardiopulmonary disease in rats with neonatal hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 305: L341L351, 2013 ...

Lanthio Pharma | Entity website

Welcome to Lanthio Pharma Lanthio Pharma is a Dutch biopharmaceutical company committed to developing and commercializing therapeutic peptides against difficult to target receptors (e.g ...

Lanthio Pharma | Entity website

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