scholarly journals HJH-1, a Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity Antimicrobial Peptide

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2026 ◽  
Author(s):  
Qing Wang ◽  
Yanzhao Xu ◽  
Mengmeng Dong ◽  
Bolin Hang ◽  
Yawei Sun ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Ph Value ◽  
Bacterial Species ◽  
Membrane Integrity ◽  
Resistant Bacteria ◽  
Bacterial Membrane ◽  
Α Subunit ◽  
Promising Alternative

With the overuse of antibiotics, multidrug-resistant bacteria pose a significant threat to human health. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. This study examines the antimicrobial and membrane activity of HJH-1, a cationic peptide derived from the hemoglobin α-subunit of bovine erythrocytes P3. HJH-1 shows potent antimicrobial activity against different bacterial species associated with infection and causes weaker hemolysis of erythrocytes, at least five times the minimum inhibitory concentration (MIC). HJH-1 has good stability to tolerance temperature, pH value, and ionic strength. The anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)] and propidium iodide are used as indicators of membrane integrity. In the presence of HJH-1 (1× MIC), Escherichia coli membranes rapidly depolarise, whereas red blood cells show gradual hyperpolarisation. Scanning electron microscopy and transmission electron micrographs show that HJH-1 (1× MIC) damaged the membranes of Escherichia coli, Staphylococcus aureus, and Candida albicans. In conclusion, HJH-1 damages the integrity of the bacterial membrane, preventing the growth of bacteria. HJH-1 has broad-spectrum antibacterial activity, and these activities are performed by changing the normal cell transmembrane potential and disrupting the integrity of the bacterial membrane.

scholarly journals In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.

scholarly journals High Colonization Rate and Heterogeneity of ESBL- and Carbapenemase-Producing Enterobacteriaceae Isolated from Gull Feces in Lisbon, Portugal

2020 ◽  
Vol 8 (10) ◽  
pp. 1487
Author(s):  
Marta Aires-de-Sousa ◽  
Claudine Fournier ◽  
Elizeth Lopes ◽  
Hermínia de Lencastre ◽  
Patrice Nordmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Encoding Genes

In order to evaluate whether seagulls living on the Lisbon coastline, Portugal, might be colonized and consequently represent potential spreaders of multidrug-resistant bacteria, a total of 88 gull fecal samples were screened for detection of extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing Enterobacteriaceae for methicillin-resistant Staphylococcus aureus (MRSA) and for vancomycin-resistant Enterococci (VRE). A large proportion of samples yielded carbapenemase- or ESBL-producing Enterobacteriaceae (16% and 55%, respectively), while only two MRSA and two VRE were detected. Mating-out assays followed by PCR and whole-plasmid sequencing allowed to identify carbapenemase and ESBL encoding genes. Among 24 carbapenemase-producing isolates, there were mainly Klebsiella pneumoniae (50%) and Escherichia coli (33%). OXA-181 was the most common carbapenemase identified (54%), followed by OXA-48 (25%) and KPC-2 (17%). Ten different ESBLs were found among 62 ESBL-producing isolates, mainly being CTX-M-type enzymes (87%). Co-occurrence in single samples of multiple ESBL- and carbapenemase producers belonging to different bacterial species was observed in some cases. Seagulls constitute an important source for spreading multidrug-resistant bacteria in the environment and their gut microbiota a formidable microenvironment for transfer of resistance genes within bacterial species.

scholarly journals Fluorescent Ion Efflux Screening Assay for Determining Membrane-Active Peptides

2017 ◽  
Vol 70 (2) ◽  
pp. 220
Author(s):  
Neil M. O'Brien-Simpson ◽  
Wenyi Li ◽  
Namfon Pantarat ◽  
Mohammed Akhter Hossain ◽  
Frances Separovic ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Solid Phase ◽  
Bacterial Species ◽  
Membrane Integrity ◽  
Membrane Model ◽  
Bacterial Membrane ◽  
Membrane Composition ◽  
Screening Assay ◽  
Ion Efflux ◽  
Membrane Interactive

A major global health threat is the emergence of antibiotic-resistant microbes. Coupled with a lack of development of modified antibiotics, there is a need to develop new antimicrobial molecules and screening assays for them. In this study, we provide proof of concept that a large unilamellar vesicle (LUV) method used to study chloride ion efflux facilitated by ionophores and surfactant-like molecules that disrupt membrane integrity can be adapted to identify membrane-interactive antimicrobial peptides (AMPs) and to screen relative activity of AMPs. Lucigenin was encapsulated in LUVs in the presence of Cl– ion (NaCl), which quenches fluorescence, and then incubated with AMPs in 100 mM NaNO3 buffer. Upon AMP membrane interaction or disruption, the Cl– ion is exchanged with the NO3– ion, and the resultant lucigenin fluorescence is indicative of relative AMP activity. Seven AMPs were synthesized by solid-phase peptide chemistry and incubated with LUVs of different phospholipid compositions. Each AMP resulted in lucigenin fluorescence, which was dose dependent, and the relative fluorescence correlated with the minimum inhibitory concentration and minimum bactericidal concentration values for the corresponding peptide. Furthermore, using mammalian model phospholipid LUVs, lucigenin-induced fluorescence also correlated with the AMP cytotoxicity half-maximal inhibitory concentration values. The proline-rich AMP, Chex1-Arg20, which is non-lytic but interacts with the bacterial membrane resulted in lucigenin fluorescence of bacterial membrane model LUVs but not of mammalian membrane model LUVs. The fluorescent ion efflux assay developed here should have applicability for most AMPs and could be tailored to target particular bacterial species membrane composition, potentially leading to the identification of novel membrane-interactive AMPs. The rapid high-throughput method also allows for screening of relative AMP activity and toxicity before biological testing.

scholarly journals Evaluation of Antimicrobial Potential of the Marine Cyanobacterium, Rivularia mesenterica

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Mirjana Skočibušić ◽  
Sandra Lacić ◽  
Zorica Rašić
Keyword(s):  
Antimicrobial Activity ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Marine Cyanobacterium ◽  
Gram Positive ◽  
Promising Alternative ◽  
Gram Negative ◽  
Antimicrobial Potential ◽  
Ethanol Extracts ◽  
Promising Source

Background: Antibiotic resistance is becoming a pivotal concern for public health accelerating the search for new antimicrobial molecules from nature. The prevention and treatment of infectious diseases by applying products from marine organisms, especially Cyanobacteria as a potential and promising source of antimicrobial agents appears as a possible alternative. Aims: To evaluate the in vitro antimicrobial potential of different extracts derived from marine cyanobacterium Rivularia mesenterica against Gram-positive and Gram-negative bacteria, including multidrug resistant bacteria, by comparison with clinically relevant antibiotics.   Methodology: The secondary metabolites were extracted from fresh and dried cyanobacterial biomass in water and different organic solvents. Antimicrobial efficacy of different extracts was evaluated by the disc diffusion assay. Additionally, the minimum inhibitory concentrations (MIC) of the ethanol extracts obtained from fresh and dried biomass was also determined. Results: The ethanol extracts obtained from fresh and dried biomass of R. mesenterica showed significant antimicrobial activity against five Gram-positive and five antibiotic resistant Gram-negative bacteria and four fungal strains in comparison with the clinically relevant antibiotics. The inhibitory effect of the ethanol extracts was observed, with MIC values in the range 0.06 to 32.00 μg/ml against tested strains. Furthermore, the water extract was inactive against of the tested bacteria and fungi. Conclusion: These results suggest that the ethanol extracts of R. mesenterica possess potent broad spectrum of antimicrobial activity, which can serve as an interesting source for antimicrobial compounds and promising alternative to synthetic antimicrobial drugs discovery.

scholarly journals Expression of mouse beta defensin 2 in Escherichia coli and its broad-spectrum antimicrobial activity

2011 ◽  
Vol 42 (3) ◽  
pp. 1180-1187 ◽  
Author(s):  
Tianxiang Gong ◽  
Wanyi Li ◽  
Yueling Wang ◽  
Yan Jiang ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Broad Spectrum

scholarly journals Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli

2020 ◽  
Author(s):  
Caroline Boulouis ◽  
Wan Rong Sia ◽  
Muhammad Yaaseen Gulam ◽  
Jocelyn Qi Min Teo ◽  
Thanh Kha Phan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Granzyme B ◽  
Carbapenem Resistance ◽  
Effector Proteins ◽  
Resistant Bacteria ◽  
E Coli ◽  
Mait Cells ◽  
Mait Cell

AbstractMucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans, and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity against E. coli clinical strains in a manner dependent on the activity of cytolytic proteins, but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to TCR-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-living E. coli. Furthermore, MAIT cell-mediated bacterial control extend to multidrug-resistant E. coli primary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistant E. coli susceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity, and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance in E. coli.One Sentence SummaryPotent antimicrobial activity of human MAIT cells overcomes carbapenem-resistance in control of Escherichia coli

scholarly journals Nybomycin Inhibits both Fluoroquinolone-Sensitive and Fluoroquinolone-Resistant Escherichia coli DNA Gyrase

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dmitrii I. Shiriaev ◽  
Alina A. Sofronova ◽  
Ekaterina A. Berdnikovich ◽  
Dmitrii A. Lukianov ◽  
Ekaterina S. Komarova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Resistant Bacteria ◽  
Mutant Form ◽  
Wild Type ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type

ABSTRACT Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics, including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in health care; therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery. Nybomycins are an attractive class of compounds, reported to be “reverse antibiotics” that selectively inhibit growth of some Gram-positive FQ-resistant bacteria by targeting the mutant form of DNA gyrase while being inactive against wild-type strains with FQ-sensitive gyrases. The strong “reverse” effect was demonstrated only for a few Gram-positive organisms resistant to FQs due to the S83L/I mutation in the GyrA subunit of DNA gyrase. However, the activity of nybomycins has not been extensively explored among Gram-negative species. Here, we observed that in a ΔtolC strain of the Gram-negative Escherichia coli with enhanced permeability, wild-type gyrase and a GyrA S83L mutant, resistant to fluoroquinolones, are similarly sensitive to nybomycin.

scholarly journals Characterizing the Mechanism of Action of an Ancient Antimicrobial, Manuka Honey, against Pseudomonas aeruginosa Using Modern Transcriptomics

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Daniel Bouzo ◽  
Nural N. Cokcetin ◽  
Liping Li ◽  
Giulia Ballerin ◽  
Amy L. Bottomley ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Manuka Honey ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACT Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa. We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa. These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance. IMPORTANCE The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.

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