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Published on: August 11, 2018
In Silico and In Vitro Analyses Reveal Promising Antimicrobial Peptides from Myxobacteria
Benita S Arakal1, David E Whitworth2, Philip E James1
1School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.
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.
Insights
Antimicrobial peptides (AMPs) from predatory myxobacteria show promise as novel antimicrobial agents. While in vitro activity against bacteria was moderate, these AMPs effectively reduced bacterial biofilms, offering an alternative to traditional antibiotics.
Area of Science:
- Microbiology
- Biochemistry
- Genomics
Background:
- Antimicrobial resistance (AMR) necessitates the development of alternative antimicrobial agents.
- Predatory myxobacteria are a potential source of novel antimicrobial compounds.
Purpose of the Study:
- To investigate potential antimicrobial peptides (AMPs) from myxobacterial genomes using in silico methods.
- To characterize the predicted antimicrobial, anti-inflammatory, antifungal, and cytotoxic properties of these AMPs.
Main Methods:
- In silico analysis of eight complete myxobacterial genomes to extract AMP sequences.
- Prediction of AMP activity against various pathogens, including Klebsiella pneumoniae and Staphylococcus aureus.
- In vitro synthesis and testing of selected AMPs for minimum inhibitory concentration (MIC) and antibiofilm activity.
Main Results:
- Identified 672 potential AMP sequences, with 117 predicted as 'potent putative AMPs' with broad-spectrum activity.
- Potent putative AMPs showed predicted anti-inflammatory and antifungal properties, but not antiviral activity.
- In vitro assays revealed moderate MIC values but significant antibiofilm activity for synthesized AMPs, outperforming traditional antibiotics in biofilm reduction.
Conclusions:
- Myxobacteria-derived AMPs represent a promising source for novel antimicrobial agents.
- These AMPs exhibit potent antibiofilm properties, offering a potential strategy to combat bacterial infections.
- Further research into myxobacterial AMPs could lead to new therapeutic strategies against resistant pathogens.
