Medicinal leech antimicrobial peptides lacking toxicity represent a promising alternative strategy to combat antibiotic-resistant pathogens
Research article published in European journal of medicinal chemistry (2019)
Abstract
The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections. The ability of the medicinal leech Hirudo medicinalis to store blood for months with little change has attracted interest regarding the identification of novel AMPs in this organism. In this study, we employed computational algorithms to the medicinal leech genome assembly to identify amino acid sequences encoding potential AMPs. Then, we synthesized twelve candidate AMPs identified by the algorithms, determined their secondary structures, measured minimal inhibitory concentrations against three bacterial species (Escherichia coli, Bacillus subtilis, and Chlamydia thrachomatis), and assayed cytotoxic and haemolytic activities. Eight of twelve candidate AMPs possessed antimicrobial activity, and only two of them, 3967 (FRIMRILRVLKL) and 536-1 (RWRLVCFLCRRKKV), exhibited inhibition of growth of all tested bacterial species at a minimal inhibitory concentration of 10 μmol. Thus, we evidence the utility of the developed computational algorithms for the identification of AMPs with low toxicity and haemolytic activity in the medicinal leech genome assembly.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections.
Why This Matters for Hirudotherapy
This study applied computational algorithms to the Hirudo medicinalis genome assembly to identify sequences encoding potential antimicrobial peptides (AMPs), synthesized twelve candidates, and characterized their secondary structures, minimal inhibitory concentrations against Escherichia coli, Bacillus subtilis, and Chlamydia trachomatis, and cytotoxic and haemolytic activities. Eight peptides showed antimicrobial activity, with two exhibiting broad-spectrum growth inhibition at 10 μmol and low toxicity or hemolysis. This work is directly relevant to understanding the medicinal leech's innate immune repertoire, as such AMPs may underlie the organism's ability to preserve ingested blood for months without bacterial spoilage, and the identified peptides could represent leads against antibiotic-resistant pathogens. However, the findings are limited to in vitro characterization; no animal or human data, clinical efficacy, or therapeutic application involving leeches themselves are presented, and translation to hirudotherapy practice remains speculative.
Citation
Medicinal leech antimicrobial peptides lacking toxicity represent a promising alternative strategy to combat antibiotic-resistant pathogens.
Grafskaia E et al. · European journal of medicinal chemistry, 2019
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