Review on bibliography related to antimicrobials

In this report, a bibliographic research has been done in the field of antimicrobials.In this report, a bibliographic research has been done in the field of antimicrobials. Not all antimicrobials have been included, but those that are being subject of matter in the group GBMI in Terrassa, and others of interest. It includes chitosan and other biopolymers. The effect of nanoparticles is of great interest, and in this sense, the effect of Ag nanoparticles and antibiotic nanoparticles (nanobiotics) has been revised. The report focuses on new publications and the antimicrobial effect of peptides has been considered. In particular, the influence of antimicrobials on membranes has deserved much attention and its study using the Langmuir technique, which is of great utility on biomimetic studies. The building up of antimicrobials systems with new techniques (bottom-up approach), as the Layer-by-Layer technique, can also be found in between the bibliography. It has also been considered the antibiofilm effect, and the new ideas on quorem sensing and quorum quenching.Preprin

Peptides and Peptidomimetics for Antimicrobial Drug Design

The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics

Concerns in the Design and Development of Novel Antimicrobial Peptides

Peptide and protein based therapeutics are the most promising approaches in today medicine. Bioactive peptides can be valuable drugs in the treatment of various illnesses, such as cardiovascular and neurodegenerative diseases. Cell toxic peptides can be considered for cancer or infection therapy. Antimicrobial peptides (AMPs) are one of the most interesting antibiotic groups in this regard, especially in drug resistance infections. Numerous AMPs have been discovered from the natural source; however, artificial synthetic ones have been also developed based on rational design or bioinformatics modeling. Physicochemical features of AMPs are highly important in their antibacterial activity as well as their toxicity. The best AMP is the one that has selective potent antimicrobial bioactivity and no or least hemolytic and cytotoxic effect. In this review, various structural factors affecting the AMPs bioactivity, such as AMPs size, charge, amphipathicity, and amino acid sequence are illustrated considering the most recently published articles. Finally, the trends in AMP design and development are discussed. HIGHLIGHTS•Antimicrobial peptides are highly interesting antibiotics in multi-drug resistance infections.•Antimicrobial peptides are short peptides with less than 50 amino acids and overall positive charge.•First and second structural features of AMPs are important factors in their bioactivities.•Cyclization and branching of AMPs could affect their pharmacokinetic and pharmacodynamics

Identification of the region that plays an important role in determining antibacterial activity of bovine seminalplasmin

Seminalplasmin (SPLN) is a 47-residue protein isolated from bovine seminal plasma having potent antimicrobial activity against a broad spectrum of microorganisms. SPLN, also known as caltrin, acts as a calcium transport regulator in bovine sperms. Analysis of the sequence of SPLN reveals a 27-residue stretch with the sequence SLSRYAKLANRLANPKLLETFLSKWIG more hydrophobic than the rest of the protein. It is demonstrated that a synthetic peptide corresponding to this 27-residue segment has antimicrobial activity comparable to that of SPLN. It does not exhibit hemolytic activity at concentrations where antibacterial activity is observed. Since P27 can be conveniently obtained in large amounts by chemical synthesis, it could serve not only as a starting compound to obtain peptides with improved antibacterial activity but also to understand the role of SPLN in reproductive physiology

A polyalanine peptide derived from polar fish with anti-infectious activities

Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.National Institute of Allergy and Infectious Diseases (U.S.) (R21AI098701

Artificial intelligence-driven antimicrobial peptide discovery

Antimicrobial peptides (AMPs) emerge as promising agents against antimicrobial resistance, providing an alternative to conventional antibiotics. Artificial intelligence (AI) revolutionized AMP discovery through both discrimination and generation approaches. The discriminators aid the identification of promising candidates by predicting key peptide properties such as activity and toxicity, while the generators learn the distribution over peptides and enable sampling novel AMP candidates, either de novo, or as analogues of a prototype peptide. Moreover, the controlled generation of AMPs with desired properties is achieved by discriminator-guided filtering, positive-only learning, latent space sampling, as well as conditional and optimized generation. Here we review recent achievements in AI-driven AMP discovery, highlighting the most exciting directions

Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the "antimicrobial centre" of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library.HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C-terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more proteolytically stable peptides. However, the benefit of backbone cyclization did not extend to longer 11-mer peptides derived from the same region of lactoferricin. Mass spectrometry data support the serum stability assay results and allowed us to determine preferred proteolysis sites in the peptides. Furthermore, isothermal titration calorimetry experiments showed that the peptides all had weak interactions with albumin, the most abundant protein in human serum.Taken together, the results provide insight into the behavior of the peptides in human serum and will therefore aid in advancing antimicrobial peptide design towards systemic applications

Specific antimicrobial and hemolytic activities of 18-residue peptides derived from the amino terminal region of the toxin pardaxin

Peptides are part of the host defense system against bacteria and fungi in species right across the evolutionary scale. However, endogenous antibacterial peptides are often composed of 25 residues or more and, therefore, are not ideal for therapeutic use. Hence it is of considerable interest to design and engineer short peptides having antimicrobial activity. Peptides composed of 18 amino acids, derived from the N-terminal region of the 33-residue toxiri pardaxin (PX), GFFALIPKDSSPLFKTLLSAVGSALSSSGEQE, were synthesized and examined for biological activities. Peptide corresponding to the 1-18 stretch of PX exhibited antimicrobial activity only against Escherichia coli and not against Gram-positive microorganisms. The peptide also did not possess hemolytic activity. Replacement of P7 by A resulted in a peptide possessing both antibacterial and hemolytic activity. Substitution of both K residues by Q in the 'A' analog resulted in a peptide having peptides and investigation of their model membrane permeabilizing activities indicated that selective activity can be explained by their biophysical properties. Hence, by a rational design approach based on biophysical principles, it should be possible to generate short peptides having specific biological activity

Broad-spectrum antimicrobial activity and improved stability of a D-Amino acid enantiomer of DMPC-10A, the designed derivative of dermaseptin truncates

DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens