Small cationic antimicrobial peptides delocalize peripheral membrane proteins
Michaela Wenzel,Alina Iulia Chiriac,Andreas Otto,Dagmar Zweytick,Caroline May,Catherine Schumacher,Ronald Gust,H. Bauke Albada,Maya Penkova,Ute Krämer,Ralf Erdmann,Nils Metzler-Nolte,Suzana K. Straus,Erhard Bremer,Dörte Becher,Heike Brötz-Oesterhelt,Hans-Georg Sahl,Julia E. Bandow +17 more
TLDR
It is shown that peptide integration into the membrane causes delocalization of essential peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell- wall integrity.Abstract:
Short antimicrobial peptides rich in arginine (R) and tryptophan (W) interact with membranes. To learn how this interaction leads to bacterial death, we characterized the effects of the minimal pharmacophore RWRWRW-NH2. A ruthenium-substituted derivative of this peptide localized to the membrane in vivo, and the peptide also integrated readily into mixed phospholipid bilayers that resemble Gram-positive membranes. Proteome and Western blot analyses showed that integration of the peptide caused delocalization of peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell-wall integrity. This delocalization phenomenon also was observed with the cyclic peptide gramicidin S, indicating the generality of the mechanism. Exogenous glutamate increases tolerance to the peptide, indicating that osmotic destabilization also contributes to antibacterial efficacy. Bacillus subtilis responds to peptide stress by releasing osmoprotective amino acids, in part via mechanosensitive channels. This response is triggered by membrane-targeting bacteriolytic peptides of different structural classes as well as by hypoosmotic conditions.read more
Citations
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Human commensals producing a novel antibiotic impair pathogen colonization
Alexander Zipperer,Martin C. Konnerth,Claudia Laux,Anne Berscheid,Daniela Janek,Daniela Janek,Christopher Weidenmaier,Marc Burian,Nadine A. Schilling,Christoph Slavetinsky,Matthias Marschal,Matthias Willmann,Hubert Kalbacher,Birgit Schittek,Heike Brötz-Oesterhelt,Stephanie Grond,Andreas Peschel,Bernhard Krismer +17 more
TL;DR: It is shown that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria.
Journal ArticleDOI
The value of antimicrobial peptides in the age of resistance
Maria Magana,Muthuirulan Pushpanathan,Ana L. Santos,Leon G. Leanse,Michael Fernandez,Anastasios Ioannidis,Marc A. Giulianotti,Yiorgos Apidianakis,Steven B. Bradfute,Andrew L. Ferguson,Artem Cherkasov,Mohamed N. Seleem,Clemencia Pinilla,Cesar de la Fuente-Nunez,Themis Lazaridis,Themis Lazaridis,Tianhong Dai,Richard A. Houghten,Robert E. W. Hancock,George P. Tegos +19 more
TL;DR: The benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens are identified, advances in the deployment of novel promising antimacterial peptides are highlighted, and the needs and priorities in designing focused development strategies taking into account the most advanced tools available are underlined.
Journal ArticleDOI
Antimicrobial Peptides: Mechanisms of Action and Resistance:
TL;DR: Recent advances in understanding of the diverse mechanisms of action of cationic AMPs are described and the bacterial resistance against these peptides and the recently developed peptide GL13K is used as an example.
Journal ArticleDOI
Daptomycin inhibits cell envelope synthesis by interfering with fluid membrane microdomains
Anna Müller,Michaela Wenzel,Henrik Strahl,Fabian Grein,Terrens N. V. Saaki,Bastian Kohl,Tjalling Siersma,Julia E. Bandow,Hans-Georg Sahl,Tanja Schneider,Leendert W. Hamoen +10 more
TL;DR: It is reported that daptomycin perturbs fluid microdomains in bacterial cell membranes, thereby interfering with membrane-bound cell wall and lipid synthesis processes, and adding a different perspective as to how membrane-active antibiotics can kill bacteria.
Journal ArticleDOI
Antimicrobial Peptides Targeting Gram-Positive Bacteria.
Nermina Malanovic,Karl Lohner +1 more
TL;DR: The multifaceted mode of actions will make AMPs superior to antibiotics that act only on one specific target, whereupon most of these peptides are supposed to kill bacteria via membrane damage.
References
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Journal ArticleDOI
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Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action.
TL;DR: In this review, the structures of a number of different Trp- and Arg-rich antimicrobial peptides are examined and some of the major mechanistic studies are presented.
Journal ArticleDOI
Activities of LL-37, a Cathelin-Associated Antimicrobial Peptide of Human Neutrophils
TL;DR: The broad-spectrum antimicrobial properties of LL-37, its presence in neutrophils, and its inducibility in keratinocytes all suggest that this peptide and its precursor (hCAP-18) may protect skin and other tissues from bacterial intrusions and LPS-induced toxicity.
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Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions
TL;DR: Identifying and harnessing highly conserved or species-specific structural features of CWGs offers excellent opportunities for developing new antibiotics, vaccines and diagnostics for use in the fight against severe infectious diseases, such as sepsis, pneumonia, anthrax and tuberculosis.