In Silico and In Vitro Analyses Reveal Promising Antimicrobial Peptides from Myxobacteria

Abstract

Antimicrobial resistance (AMR) is a global concern, and as soon as new antibiotics are introduced, resistance to those agents emerges. Therefore, there is an increased appetite for alternative antimicrobial agents to traditional antibiotics. Here, we used in silico methods to investigate potential antimicrobial peptides (AMPs) from predatory myxobacteria. Six hundred seventy-two potential AMP sequences were extracted from eight complete myxobacterial genomes. Most putative AMPs were predicted to be active against Klebsiella pneumoniae with least activity being predicted against Staphylococcus aureus. One hundred seventeen AMPs (defined here as ‘potent putative AMPs’) were predicted to have very good activity against more than two bacterial pathogens, and these were characterized further in silico. All potent putative AMPs were predicted to have anti-inflammatory and antifungal properties, but none was predicted to be active against viruses. Twenty six (22%) of them were predicted to be hemolytic to human erythrocytes, five were predicted to have anticancer properties, and 56 (47%) were predicted to be biofilm active. In vitro assays using four synthesized AMPs showed high MIC values (e.g. So_ce_56_913 250 µg/ml and Coral_AMP411 125 µg/ml against E. coli). However, antibiofilm assays showed a substantial reduction in numbers (e.g. Coral_AMP411 and Myxo_mac104 showed a 69% and 73% reduction, respectively, at the lowest concentration against E. coli) compared to traditional antibiotics. Fourteen putative AMPs had high sequence similarity to proteins which were functionally associated with proteins of known function. The myxobacterial genomes also possessed a variety of biosynthetic gene clusters (BGCs) that can encode antimicrobial secondary metabolites, but their numbers did not correlate with those of the AMPs. We suggest that AMPs from myxobacteria are a promising source of novel antimicrobial agents with a plethora of biological properties.

Machine learning assisted rational design of antimicrobial peptides based on human endogenous proteins and their applications for cosmetic preservative system optimization

“…Capecchi et al trained recurrent neural networks (RNN) using data from the Database of Antimicrobial Activity and Structure of Peptides to design short non-haemolytic AMPs 55 . A recent study used in silico methods to investigate potential AMPs against predatory myxobacteria 56 . The sources of AMPs are diverse.…”

Design and Synthesis of Novel Antimicrobial Agents

“…For the careful and effective development and preservation of AMPs-based products, further research needs to be conducted. AMPs from predatory myxobacteria were studied in silico by Arakal et al [ 113 ]. Myxo_mac104 (VNRVTRVIATRRNEAERIGVPLYF), Stig_213 (VVKTVVSRAYTRAGLAQRLGWHDLRHSTRT), Coral_AMP411 (MMGAPTRRFKHHAWHETTVARRATARYVGGLSSRFVTR), and So_ce_56_913 (VEKSEKAISGARRG-SPIVNRHVVHLEHVRLKGPYRLSDRLSSAPRTSTRV) were used to create the four AMPs.…”

The RNA cargo of Myxococcus outer membrane vesicles

“…They possess contact-dependent mechanisms for killing prey microbes, and also secrete a cocktail of antimicrobial enzymes, peptides and secondary metabolites. [13][14][15] The OMVs produced by myxobacteria and other predators are themselves antimicrobial, being able to kill a wide range of prey organisms, and addition of myxobacterial OMVs to prey cells leads to wholesale changes in the prey transcriptome. [16][17][18][19] It is possible that myxobacterial OMVs might transfer functional RNAs into prey cells during predation, compromising their ability to defend themselves against predator attack, in an analogous fashion to pathogens using ncRNAs in OMVs to attenuate the host immune response during infection.…”

“…They possess contact-dependent mechanisms for killing prey microbes, and also secrete a cocktail of antimicrobial enzymes, peptides and secondary metabolites. 13–15 The OMVs produced by myxobacteria and other predators are themselves antimicrobial, being able to kill a wide range of prey organisms, and addition of myxobacterial OMVs to prey cells leads to wholesale changes in the prey transcriptome. 16–19…”