Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Wu, Xiaozhe; Li, Zhan; Li, Xiaolu; Tian, Yaomei; Fan, Yingzi; Yu, Chun-Hong; Zhou, Bailing; Liu, Yi; Xiang, Rong; Yang, Li

doi:10.2147/dddt.s107195

Cited by 119 publications

(80 citation statements)

References 28 publications

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“…To resolve the problem of antimicrobial resistance, multiple AMPs have been developed in recent years as alternative antibiotics (16)(17)(18)(19), and a number of AMPs exhibited high antimicrobial efficacy and broad-spectrum activity (17,20). The present study suggested that L12 was effective in susceptibility tests against gram-positive bacteria, particularly S. aureus.…”

Section: Discussionmentioning

confidence: 69%

“…The additional antibacterial molecules tested presented additive effects. A previous study demonstrated that antibacterial drugs with similar molecular mechanisms or that target the same molecular components, exert improved synergistic effects compared with combinations of drugs with dissimilar function (17). Additionally, vancomycin and ceftazidime inhibit the cell wall synthesis of gram-positive bacteria by multiple mechanisms (29), which is hypothesized to be responsible for their synergistic effects with L12.…”

Section: Discussionmentioning

confidence: 99%

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Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

Dai

et al. 2019

Mol Med Report

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Methicillin-resistant Staphylococcus aureus (S. aureus; MRSA) is one of the most common bacterial pathogens and MRSA infections are characterized by high mortality rates. Antimicrobial peptides are considered one of the most promising drugs for the treatment of resistant strains of S. aureus. The present study aimed to examine the antimicrobial activity of L12 against numerous bacterial species using the broth microdilution method. Furthermore, the synergistic effect of L12 combined with various antibacterial drugs was tested, and its antibacterial mechanism was investigated by a checkerboard assay. The alterations in bacterial morphology were detected by electron microscopy, and biofilm formation and removal were tested by crystal violet staining. The present results suggested that L12 affected the growth of gram-positive strains, particularly S. aureus. Electron microscopy analysis suggested that L12 may target the cell membrane, and L12 increased the antibacterial activity of vancomycin and levofloxacin, exerting a synergistic effect. However, the minimal inhibitory concentrations (MICs) of L12 were not correlated with antibiotic resistance, the strains resistant to more antibiotics were not more resistant to L12. A sub-MIC of L12 was able to inhibit biofilm formation in a dose-dependent manner; however, concentrations of L12 ≤10 times the MIC were not sufficient to degrade previously formed biofilm. Collectively, the present study suggested that L12 may represent a novel potential therapeutic molecule for the treatment of S. aureus infections.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

Dai

et al. 2019

Mol Med Report

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“…According to our data intercommunication was also between the terms of setting of antibacterial therapy and level of vitamin D (r = 0.57, P < 0.05), lactoferrin (r = 0.40, P < 0.05) and hBPI (r = 0.38, P < 0.05) in the blood serum. The obtained data look logical, if to take into account circumstance that antimicrobial peptides together with antibacterial preparations can show a synergistic effect in regard to pathogenic causative agents and promote effictive etiotropic therapy [27,28].…”

Section: Resultsmentioning

confidence: 97%

The prognostication of development of respiratory tract bacterial diseases for children of early age

2019

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A -research concept and design; B -collection and/or assembly of data; C -data analysis and interpretation; D -writing the article; E -critical revision of the article; F -final approval of the article The purpose of this study was definition of influence of the modified factors in development of acute pneumonia in children of early age and development of the method of prognostication of disease development.Materials and methods. 89 children of early age with acute bronchopulmonary pathology whose average age was 1.3 ± 0.2 years (47 children with acute bacterial bronchits and 42 children with acute community-acquired pneumonia) were examined. Also we tested the level of 25-hydroxyvitamin D (25(OH)D), hBPI, cathelicidin LL-37, lactoferrin in blood serum with the help of immunoenzymometric analysis. The significant factors that are most associated with the development of acute pneumonia were revealed using factor analysis. For prognostication of probability of development of an acute pneumonia the equation of logistic regression was used. Determination of quality of the received model of prognostication was conducted by means of the ROC analysis and index of AUC. For assessment of the discriminating ability of model the Gini index was calculated.Results. By results of conducted factor analysis 5 significant factors determining the main part of predictors of development of an acute pneumonia in children of early age, patients with acute inflammatory bronchopulmonary pathology were allocated. The conducted correlation analysis of variables revealed existence of interrelations between prenatal, anamnestic and immune factors which entered further mathematical model of probability of development of an acute pneumonia in children of early age. The statistical importance of the created model was confirmed by Omnibus Test, the diagnostic information content was estimated according to a ROC curve that confirmed high quality of model. Conclusion.On the basis of the conducted factor analysis the most priority predictors of development of an acute pneumonia in children of early age with acute bronchopulmonary pathology who were further included to the mathematical prognostic model of probability of development of the specified disease were allocated.Прогнозування розвитку бактеріальних захворювань органів дихання в дітей раннього віку Г. О. Леженко, А. В. Абрамов, Г. В. Крайня Мета роботи -визначення впливу модифікованих факторів у розвитку гострої пневмонії в дітей раннього віку та розроблення методу прогнозування розвитку захворювання.Матеріали та методи. Обстежили 89 дітей раннього віку з гострою бронхолегеневою патологією, середній вік яких становив 1,3 ± 0,2 року (47 дітей, які хворі на гострий бактеріальний бронхіт, і 42 дітей, які хворі на гостру позалікарняну пневмонію). За допомогою імуноферментного аналізу досліджували вміст у сироватці крові 25-гідроксивітаміну Д (25(ОН) D), hBPI, кателіцидину LL-37, лактоферину. За допомогою факторного аналізу виявили значущі фактори, що найбільше пов'язані з розвитком гострої пнев...

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“…Multidrug resistant (MDR) bacterial infections are a growing and significant threat to public health, and are caused by species including methicillin resistant S. aureus, vancomycin resistant E. faecalis, and the globally disseminated CTX-M type ESBL-expressing strains of E. coli (30, 31). Antimicrobial peptides (AMPs) are of interest as alternatives to traditional antibiotics because of their broad spectrum antimicrobial properties and efficacy against MDR bacteria; however, to date they have met limited success due to their often non-selective toxicity (32–36). We previously reported that chitosan based cationic polymers showed antimicrobial activity against a variety of MDR pathogens (12, 20–22).…”

Section: Discussionmentioning

confidence: 99%

Combined efficacy of a novel antimicrobial cationic peptide polymer with conventional antibiotics to combat multi-drug resistant pathogens

Thappeta

Vikhe

Yong

et al. 2019

Preprint

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13Antibiotic-resistant infections are predicted to kill 10 million people worldwide per year 14 by 2050 and to cost the global economy 100 trillion USD. Novel approaches and 15 alternatives to conventional antibiotics are urgently required to combat antimicrobial 16 resistance. We have synthesized a chitosan-based oligolysine antimicrobial peptide, 17 CSM5-K5, which targets multidrug resistant (MDR) bacterial species. Here we show 18 that CSM5-K5 exhibits rapid bactericidal activity against methicillin resistant 19 Staphylococcus aureus (MRSA), MDR Escherichia coli, and vancomycin resistant 20 Enterococcus faecalis (VRE). Combinatorial therapy of CSM5-K5 with antibiotics to 21 which each organism is otherwise resistant restores sensitivity to the conventional 22 antibiotic. CSM5-K5 alone significantly reduced pre-formed bacterial biofilm by two-four 23 orders of magnitude and, in combination with traditional antibiotics, reduced pre-formed 24 biofilm by more than two-three orders of magnitude at sub inhibitory concentrations. 25Moreover, using a mouse excisional wound infection model, CSM5-K5 treatment 26 reduced bacterial burdens by one to three orders of magnitude, and acted 27 synergistically with vancomycin and tetracycline to clear VRE and MDR E. coli, 28 respectively. Importantly, little to no resistance against CSM5-K5 arose for any of the 29 three MDR bacteria during 15 days of serial passage. This work demonstrates the 30 feasibility and benefits of using this synthetic cationic peptide as alternative to, or in 31 combination with, traditional antibiotics to treat infections caused by MDR bacteria. 32 33Antibiotic resistance is a threat to global public health and sustainability (1). Antibiotic 35 resistance currently accounts for an estimated 70,000 annual deaths globally, and in the 36 absence of new therapeutics, infections caused by resistant "superbugs" could kill an 37 additional 10 million people each year worldwide by 2050, surpassing cancer (2). 38 Moreover, by 2050, antibiotic resistant infections are estimated to cost up to 3.5% of the 39 global GDP, equivalent to 100 trillion USD (2). Because corporate antibiotic 40 development pipelines of have progressively declined over the past 20 years (3), there 41 is substantial interest in seeking alternative therapeutic approaches to combat these 42 multidrug resistant (MDR) pathogens. 43 44 Host-derived antimicrobial peptides (CAMPs), typically composed of cationic and 45 hydrophobic domains, have garnered interest as alternative therapies for MDR 46 infections. CAMPs are electrostatically attracted to anionic bacterial cell surfaces, 47followed by peptide insertion into the lipid bilayer via their hydrophobic residues (4, 5). 48Chitosan is a polysaccharide composed of repeating N-glucosamine, with a structure 49 similar to that of bacterial peptidoglycan. This unique feature of chitosan renders it 50 potentially compatible with the bacterial cell wall. Numerous studies have examined the 51 efficacy of chitosan-CAMP hybrids containing quaterna...

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Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Cited by 119 publications

References 28 publications

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

The prognostication of development of respiratory tract bacterial diseases for children of early age

Combined efficacy of a novel antimicrobial cationic peptide polymer with conventional antibiotics to combat multi-drug resistant pathogens

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