Large-Scale Analysis of Antimicrobial Activities in Relation to Amphipathicity and Charge Reveals Novel Characterization of Antimicrobial Peptides.

Ling-Yi Shih,Kuan Chang,Chien-Kuo Wang

doi:10.3390/molecules22112037

Ling-Yi Shih, Kuan Chang + Show 1 more

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https://doi.org/10.3390/molecules22112037

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Abstract

It has been unclear to which antimicrobial activities (e.g., anti-gram-positive bacterial, anti-gram-negative bacterial, antifungal, antiparasitic, and antiviral activities) of antimicrobial peptides (AMPs) a given physiochemical property matters most. This is the first computational study using large-scale AMPs to examine the relationships between antimicrobial activities and two major physiochemical properties of AMPs—amphipathicity and net charge. The results showed that among all kinds of antimicrobial activities, amphipathicity and net charge best differentiated between AMPs with and without anti-gram-negative bacterial activities. In terms of amphipathicity and charge, all the AMPs whose activities were significantly associated with amphipathicity and net charge were alike except those with anti-gram-positive bacterial activities. Furthermore, the higher the amphipathic value, the greater the proportion of AMPs possessing both antibacterial and antifungal activities. This dose–response-like pattern suggests a possible causal relationship—dual antibacterial and antifungal activities of AMPs may be attributable to amphipathicity. These novel findings could be useful for identifying potent AMPs computationally.

Highlights

A large-scale analysis of the biological activities of antimicrobial peptides (AMPs) has been carried out
The study demonstrated that AMPs with anti-gram-positive bacterial, anti-gram-negative bacterial, or anti-fungal activities generally possessed higher net charge and amphipathic values than their counterparts
Our results indicated that amphipathicity and cationic charge should play the most critical roles in anti-gram-negative bacterial activities than in the other antimicrobial activities of AMPs due to the largest significant differences and the smallest p-value, which is a novel finding that could only be demonstrated by large-scale AMP data

Summary

Introduction

A large-scale analysis of the biological activities of antimicrobial peptides (AMPs) has been carried out. AMPs can either kill or inhibit the growth of microbial organisms such as bacteria, fungi, parasites, and viruses. Some such as moronecidin and melittin exhibit broad-spectrum antimicrobial activities with antibacterial, antifungal, antiparasitic, and antiviral effects [1,2]; some possess limited antimicrobial effects. Until now, which property makes some AMPs effective against specific types of microbes was unclear. Large-scale bioinformatic studies on AMP physicochemical properties have been done [6,7,8,9].

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