In recent decades much attention has been paid to antimicrobial peptides (AMPs) as natural antibiotics, which are presumably protected from resistance development in bacteria. However, experimental evolution studies have revealed prompt resistance increase in bacteria to any individual AMP tested. Here we demonstrate that naturally occurring compounds containing insect AMP complexes have clear advantage over individual peptide and small molecule antibiotics in respect of drug resistance development. As a model we have used the compounds isolated from bacteria challenged maggots of Calliphoridae flies. The compound isolated from blow fly Calliphora vicina was found to contain three distinct families of cell membrane disrupting/permeabilizing peptides (defensins, cecropins and diptericins), one family of proline rich peptides and several unknown antimicrobial substances. Resistance changes under long term selective pressure of the compound and reference antibiotics cefotaxime, meropenem and polymyxin B were tested using Escherichia coli, Klebsiella pneumonia and Acinetobacter baumannii clinical strains. All the strains readily developed resistance to the reference antibiotics, while no signs of resistance growth to the compound were registered. Similar results were obtained with the compounds isolated from 3 other fly species. The experiments revealed that natural compounds containing insect AMP complexes, in contrast to individual AMP and small molecule antibiotics, are well protected from resistance development in bacteria. Further progress in the research of natural AMP complexes may provide novel solutions to the drug resistance problem.
Biofilms, sedimented microbial communities embedded in a biopolymer matrix cause vast majority of human bacterial infections and many severe complications such as chronic inflammatory diseases and cancer. Biofilms’ resistance to the host immunity and antibiotics makes this kind of infection particularly intractable. Antimicrobial peptides (AMPs) are a ubiquitous facet of innate immunity in animals. However, AMPs activity was studied mainly on planktonic bacteria and little is known about their effects on biofilms. We studied structure and anti-biofilm activity of AMP complex produced by the maggots of blowfly Calliphora vicina living in environments extremely contaminated by biofilm-forming germs. The complex exhibits strong cell killing and matrix destroying activity against human pathogenic antibiotic resistant Escherichia coli, Staphylococcus aureus and Acinetobacter baumannii biofilms as well as non-toxicity to human immune cells. The complex was found to contain AMPs from defensin, cecropin, diptericin and proline-rich peptide families simultaneously expressed in response to bacterial infection and encoded by hundreds mRNA isoforms. All the families combine cell killing and matrix destruction mechanisms, but the ratio of these effects and antibacterial activity spectrum are specific to each family. These molecules dramatically extend the list of known anti-biofilm AMPs. However, pharmacological development of the complex as a whole can provide significant advantages compared with a conventional one-component approach. In particular, a similar level of activity against biofilm and planktonic bacteria (MBEC/MIC ratio) provides the complex advantage over conventional antibiotics. Available methods of the complex in situ and in vitro biosynthesis make this idea practicable.
Цель. Определить распространенность устойчивости к антибиотикам и продукции основных приобретенных механизмов резистентности (бета-лактамаз расширенного спектра [БЛРС] и карбапенемаз) у нозокомиальных штаммов Enterobacterales, а также генотипы и принадлежность к «международным клонам высокого риска» карбапенемазопродуцирующих штаммов Klebsiella pneumoniae, выделенных в различных регионах России в рамках многоцентрового эпидемиологического исследования «МАРАФОН 2015-2016». Материалы и методы. Всего исследовано 2786 неповторяющихся изолятов энтеробактерий, включая 1316 изолятов Klebsiella pneumoniae и 837 изолятов Escherichia coli, выделенных в 49 стационарах 25 городов России в 2015-2016 гг. Видовую идентификацию изолятов проводили методом MALDI-TOF масс-спектрометрии. Определение чувствительности выполняли референтным методом микро
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