In silico study on pH-based alanine scanning of Phylloseptin-2 helps determine potential mutant sites for futuristic therapeutic analogues
Authors: Ranade, Shruti Sunil; Ramalingam, Rajasekaran
Analogues of Phylloseptins (PS), membranolytic antimicrobial peptides (AMPs), could replace antibiotics and combat growing multi-drug resistance in urinary tract infections. This study identifies potential mutant sites in a PS scaffold for generation of its analogues, using in silica alanine scanning mutagenesis. Initially, a PS scaffold from native peptides-PS1, PS2 and PS3, is identified using pH-based secondary structure (SS) profiles and conformational free energies after a 20 ns molecular dynamics (MD) simulation at 310 K. PS2 is identified as structurally stable scaffold. Further, alanine scanning is carried out for 17 amino acid residues, at varying pH for 10 ns MD simulation at 310 K to identify structurally and functionally significant and non-significant amino acids in PS2. H-bond occupancy and polar surface area are used as structural and functional parameters in the study. The statistical significance is determined using paired t-tests,using confidence interval of 90%. It was found that the amino acids viz., Leu (4), Val (16) and His (17), were structurally and functionally non-significant (P > .1). Thus, the positions of these aforementioned amino acids in addition to amino acids viz., Ala (8) and Ala (11), can be used as potential mutant sites for generation of therapeutic analogues of PS2.
Understanding of Colistin Usage in Food Animals and Available Detection Techniques: A Review
Authors: Kumar, Harsh; Chen, Bing-Huei; Kuca, Kamil; Nepovimova, Eugenie; Kaushal, Ankur; Nagraik, Rupak; Bhatia, Shashi Kant; Dhanjal, Daljeet Singh; Kumar, Vinod; Kumar, Anil; Upadhyay, Navneet Kumar; Verma, Rachna; Kumar, Dinesh
Simple Summary Colistin is a last resort drug for the treatment of infection caused by multidrug-resistant Gram-negative bacteria. Different studies have uncovered the negative impact of colistin consumption in animals. Therefore, it has become essential to monitor the dosing regimens of colistin and assess their negative effects. The current review intends to provide brief information of colistin usage and its associated negative impact and discuss available techniques to detect colistin in animal-based food so that effective preventive measures can be taken to minimize the health risks in both animals and humans. Progress in the medical profession is determined by the achievements and effectiveness of new antibiotics in the treatment of microbial infections. However, the development of multiple-drug resistance in numerous bacteria, especially Gram-negative bacteria, has limited the treatment options. Due to this resistance, the resurgence of cyclic polypeptide drugs like colistin remains the only option. The drug, colistin, is a well-known growth inhibitor of Gram-negative bacteria like Acinetobacter baumanni, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Technological advancements have uncovered the role of the mcr-1(mobilized colistin resistance) gene, which is responsible for the development of resistance in Gram-negative bacteria, which make them distinct from other bacteria without this gene. Additionally, food animals have been determined to be the reservoir for colistin resistance microbes, from which they spread to other hosts. Due to the adverse effects of colistin, many developed countries have prohibited its usage in animal foods, but developing countries are still using colistin in animal food production, thereby imposing a major risk to the public health. Therefore, there is a need for implementation of sustainable measures in livestock farms to prevent microbial infection. This review highlights the negative effects (increased resistance) of colistin consumption and emphasizes the different approaches used for detecting colistin in animal-based foods as well as the challenges associated with its detection.