Designed Antimicrobial Peptides: A New Horizon
Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters in Cosmetic Formulation, 2019
Antimicrobial peptides, also known as host defense peptides, are evolutionarily highly conserved components of the innate immune system and provide the first line of defense against invading pathogens in all multicellular organisms (Zasloff, 2002). Their significance in host defense is underscored in plants and insects by their ability to live in bacterial environments without lymphocytes and antibodies. Over the last 25 years, a great deal of information has been published describing naturally occurring peptides that possess antimicrobial activity (Blondelle et al., 1996; Kagan et al., 1994; Zasloff, 1987). AMPs exist in a range of sizes but are, in general, between 20 and 40 amino acids in length. AMPs have direct antimicrobial activities and are able to kill both Gram-negative and Gram-positive bacteria, including multidrug-resistant strains, mycobacteria (including Mycobacterium tuberculosis), enveloped viruses, parasites and fungi (Jenssen et al., 2006).
Secreted effectors of the innate mucosal barrier
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Antimicrobial peptides collectively form a diverse population of gene-encoded protein effectors with selective microbicidal effects against bacteria and fungi. Varied epithelia release antimicrobial peptides onto mucosal surfaces, and evidence increasingly implicates them as components of a biochemical barrier against microbial challenges. Although antimicrobial peptide primary structures vary greatly (Figure 4.5), they have broad-spectrum microbicidal activities in vitro, generally at low micromolar concentrations, and most are 5 kDa or less, cationic at neutral pH, and amphipathic. Mammalian antimicrobial peptide structures range from linear, disordered peptides that form α-helices in membrane-mimetic hydrophobic environments to molecules such as defensins which consist of antiparallel β-sheet-containing peptides that are constrained by up to four disulfide bonds. Certain antimicrobial peptides may be expressed constitutively or they may be inducible by exposure to bacteria or microbial antigens. Most antimicrobial peptides kill their target cells by peptide-mediated membrane disruption, creating defects that dissipate cellular electrochemical gradients, leading to microbial cell death. Despite their diverse primary, secondary, and tertiary structures, their amphipathicity enables the peptides to interact with and disrupt microbial cell membranes. There are two major families of antimicrobial peptides in mammals: cathelicidins and defensins (see Figure 4.5).
Synthesis of Bioactive Peptides for Pharmaceutical Applications
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Recently, bioactive peptides of animals, plants, and microorganism origins are significantly utilized in the treatment and prevention of cardiovascular diseases, cancer and infections (Cicero et al., 2017). Likewise, antimicrobial peptides with enhanced bioactivity are used to inhibit the growth of harmful microbes and prevent the widespread of their associated diseases (Haney et al., 2017). Hence, researchers are utilizing bioactive peptides as an alternate to conventional pharmaceutical entities to develop peptide-based treatment approaches. Thus, the current chapter is an overview of current synthesis methods that are used to synthesize bioactive peptides as they are the determining factor that elevates their bioactivity. Further, the procedures employed for the refinement, characterization and formulation of bioactive peptides in recent times and their pharmaceutical applications are also presented. Additionally, the existing challenges and the bioactive peptides in the future of pharmaceutical industry are also discussed.
Salivary human beta-defensins and cathelicidin levels in relation to periodontitis and type 2 diabetes mellitus
Published in Acta Odontologica Scandinavica, 2020
Dogukan Yilmaz, Ali Orkun Topcu, Emine Ulku Akcay, Mustafa Altındis, Ulvi Kahraman Gursoy
Antimicrobial peptides are small cationic molecules, which exist in almost all organisms [1]. There are over 45 antimicrobial peptides found in human body, of these human beta-defensins (hBDs) and cathelicidin (LL-37) play important role to establish homeostasis [2]. In the oral cavity, hBD 1-3 and LL-37 are found in gingival epithelium, gingival crevicular fluid (GCF) and saliva [3,4]. hBDs and LL-37 are multifunctional peptides and besides their well-known antimicrobial effect, they contribute to innate and adaptive immunity by enhancing phagocytosis, suppressing production of proinflammatory cytokines, and by regulating complement system [5]. They act as chemoattractants for immune cells and stimulate wound healing and angiogenesis [6]. Despite their well-defined effects on immunity, the question of how periodontitis and related factors do regulate the salivary antimicrobial peptides levels is left unexplained [7–10].
A polymicrobial view of disease potential in Crohn's-associated adherent-invasive E. coli
Published in Gut Microbes, 2018
Wael Elhenawy, Alexander Oberc, Brian K. Coombes
Antimicrobial peptides are host defense peptides that are capable of killing microbes by disrupting their membrane integrity and are often enriched in the gut during inflammation.56 Many enteric pathogens can evade killing by these bactericidal molecules using enzymatic modification systems that alter surface chemistry of lipopolysaccharide, and by outer membrane proteases that cleave dibasic sites within the core of these cationic peptides. AIEC strain NRG857c, one of two prototype strains that have been fully sequenced, has high levels of resistance towards several antimicrobial peptides that are common in the gut.57 Resistance to this arm of innate host defense in this particular strain is mediated by a plasmid-based genomic island (PI-6) that encodes an outer membrane protease (ArlC) and a Mig-14 family protein (ArlA). Mig-14 homologs are involved in antimicrobial peptide resistance in multiple bacteria, yet their mode of action is not fully understood.
Promising treatment strategies to combat Staphylococcus aureus biofilm infections: an updated review
Published in Biofouling, 2020
P. S. Seethalakshmi, Riya Rajeev, George Seghal Kiran, Joseph Selvin
NO can inhibit biofilm formation at high concentrations, therefore NO-releasing compounds have been evaluated for anti-biofilm strategies (Jardeleza et al. 2011). One of the main complications in its clinical application is the unavailability of a delivery system that can support its localized and systemic delivery in therapy (Saraiva et al. 2011). Antimicrobial peptides like japonicin-2LF, phylloseptin-PTa, and synthetic peptides like PS1-2 have been evaluated for anti-biofilm activities, and are proven to be highly effective under in vivo conditions (Galdiero et al. 2019; Park et al. 2019). The drawbacks of antimicrobial peptides in clinical therapy include ecological toxicities and their instability in human body fluids (Galdiero et al. 2019). Enzymes targeting the matrix of biofilms like dispersin B, DNase, lysostaphin, proteinase K, and trypsin are effective in dispersing biofilms of S. aureus (Kiedrowski and Horswill 2011). The use of enzymes as anti-biofilm agents include certain limitations such as high cost, and also the dispersal of cells from biofilm due to enzymatic activity can lead to infections when used under in vivo conditions (Kaplan 2009).
Related Knowledge Centers
- Eukaryote
- Immunotherapy
- Innate Immune System
- Peptide
- Prokaryote
- Antimicrobial
- Gram-Negative Bacteria
- Gram-Positive Bacteria
- Biological Membrane
- Transmembrane Channels