The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Robert E. W. Hancock - One of the best experts on this subject based on the ideXlab platform.
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Expression of an engineered heterologous Antimicrobial peptide in potato alters plant development and mitigates normal abiotic and biotic responses.
PLOS ONE, 2013Co-Authors: Ravinder K. Goyal, Robert E. W. Hancock, Autar K. Mattoo, Santosh K. MisraAbstract:Antimicrobial Cationic Peptides (AMPs) are ubiquitous small proteins used by living cells to defend against a wide spectrum of pathogens. Their amphipathic property helps their interaction with negatively charged cellular membrane of the pathogen causing cell lysis and death. AMPs also modulate signaling pathway(s) and cellular processes in animal models; however, little is known of cellular processes other than the pathogen-lysis phenomenon modulated by AMPs in plants. An engineered heterologous AMP, msrA3, expressed in potato was previously shown to cause resistance of the transgenic plants against selected fungal and bacterial pathogens. These lines together with the wild type were studied for growth habits, and for inducible defense responses during challenge with biotic (necrotroph Fusarium solani) and abiotic stressors (dark-induced senescence, wounding and temperature stress). msrA3expression not only conferred protection against F. solani but also delayed development of floral buds and prolonged vegetative phase. Analysis of select gene transcript profiles showed that the transgenic potato plants were suppressed in the hypersensitive (HR) and reactive oxygen species (ROS) responses to both biotic and abiotic stressors. Also, the transgenic leaves accumulated lesser amounts of the defense hormone jasmonic acid upon wounding with only a slight change in salicylic acid as compared to the wild type. Thus, normal host defense responses to the pathogen and abiotic stressors were mitigated by msrA3 expression suggesting MSRA3 regulates a common step(s) of these response pathways. The stemming of the pathogen growth and mitigating stress response pathways likely contributes to resource reallocation for higher tuber yield.
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Cationic bactericidal Peptides.
Advances in Microbial Physiology, 2008Co-Authors: Robert E. W. Hancock, T. Falla, Melissa H BrownAbstract:Publisher Summary This chapter provides a detailed overview of the known polyCationic Peptides, with emphasis on those of less than 100 amino acids and with a net charge greater than +2. Cationic Peptides can be classified into several groups on the basis of sequence similarities, secondary and tertiary structure, function and origin. These Peptides possess Antimicrobial activity against many species, including bacteria (Gram-positive and -negative), fungi, and viruses and, in the case of the more potent Peptides, can have a lytic activity on mammalian cells. The oxygen-independent microbicidal host defence mechanism of mammals involves several proteinaceous molecules that are Cationic in nature. These include lysozyme, bactericidal/permeability increasing factor (BPI), cathepsin G, CAP-37, lactoferrin, defensins and the eosinophil-derived proteins: the major basic protein (MBP) and the eosinophil Cationic protein (ECP). Members of the defensin family possess a secondary structure rich in P-pleated sheet, which is stabilized by these intramolecular disulphide bonds. Defensins kill a wide variety of bacteria, fungi, spirochaetes, and viruses. They exert not only microbicidal activity because of permeabilization of biological membranes but they also possess chemotactic and endocrine regulatory activities. A range of inducible Antimicrobial Cationic Peptides has been isolated—including attacins, cecropins, coleoptericin, diptericins, drosocin, phormicins, sarcotoxins, sapecins, and insect defensins. One of the main groups of antibacterial components in the insect humoral response is the cecropins. These molecules constitute a class separate and differ from other bacteriolytic Peptides produced by insects by not lysing mammalian cells. The chapter discusses occurrence of Cationic Peptides in nature, structure-function relationships of Cationic bactericidal Peptides, and interactions with lipids and membranes with these Peptides.
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clinical development of Cationic Antimicrobial Peptides from natural to novel antibiotics
Current Drug Targets - Infectious Disorders, 2002Co-Authors: Robert E. W. Hancock, Aleksander PatrzykatAbstract:Over the past decade, levels of bacterial resistance to antibiotics have risen dramatically and "superbugs" resistant to most or all available agents have appeared in the clinic. Thus there is a growing need to discover and introduce new drugs. One potential source of novel antibiotics is the Cationic Antimicrobial Peptides, which have been isolated from most living entities as components of their non-specific defenses against infectious organisms. Based on these natural templates, scores of structurally diverse Antimicrobial Cationic Peptides have been designed, manufactured both chemically and biologically, and tested for activity against specific pathogens. A few of these peptide antibiotics have entered clinical trials to date, with mixed success. However, their diverse portfolio of structures, activity spectra, biological activities, and modes of action, provide substantial potential. With the dramatic rise of antibiotic resistance, including the emergence of untreatable infections by multi-resista nt tuberculosis and vancomycin-resistant Enterococcus strains there is no doubt we need novel Antimicrobials (1). Prior to 1999, no new structural class of antibiotic had been introduced into medical practice in 30 years. At present there are four structurally novel classes of antibiotics entering the clinic, three of these being the lipopeptide daptomycin, the oxazolidinone, linezolid, and the streptogramins. With the increasing recognition of the central role of Cationic Antimicrobial Peptides in preventing the onset of infection in
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role of membranes in the activities of Antimicrobial Cationic Peptides
Fems Microbiology Letters, 2002Co-Authors: Robert E. W. Hancock, Annett RozekAbstract:Cationic amphiphilic Peptides that are found throughout nature have very broad-spectrum activities against microbes. The initial sites of interaction are with microbial membranes. Although dogma suggests that their lethal action involves disruption of the cytoplasmic membranes, a number of Cationic Peptides can traverse intact membranes to interact with internal targets.
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role of pseudomonas aeruginosa phop phoq in resistance to Antimicrobial Cationic Peptides and aminoglycosides
Microbiology, 2000Co-Authors: Emma L A Macfarlane, Agnieszka Kwasnicka, Robert E. W. HancockAbstract:Resistance to the polyCationic antibiotic polymyxin B and expression of the outer-membrane protein OprH in the opportunistic pathogen Pseudomonas aeruginosa both involve the PhoP-PhoQ two-component regulatory system. The genes for this system form an operon with oprH, oprH-phoP-phoQ, that responds to Mg2+ starvation and PhoP levels. In this study, the Mg2+-regulated promoter for this operon was mapped upstream of oprH by primer-extension experiments. An oprH::xylE-GmR mutant H855 was constructed and measurement of the catechol 2,3-dioxygenase activity expressed from this transcriptional fusion provided evidence for a second, weak promoter for phoP-phoQ. Wild-type P. aeruginosa PAO1 strain H103 was found to exhibit Mg2+-regulated resistance to the α-helical Antimicrobial Cationic peptide CP28 in addition to its previously characterized resistance to polymyxin B. Resistance to this peptide was unchanged in the OprH-null mutant H855 and a PhoP-null mutant H851. In contrast, PhoQ-null mutant H854 demonstrated constitutive CP28 resistance. Northern blot analysis revealed constitutive expression of phoP in this strain, implicating PhoP-PhoQ in the resistance of P. aeruginosa to Cationic Peptides. Furthermore, all three null-mutant strains demonstrated increased resistance to the aminoglycoside antibiotics streptomycin, kanamycin and amikacin. Two additional mutant strains, H895 and H896, were constructed that carried unmarked deletions in oprH and were found to exhibit aminoglycoside susceptibility equivalent to that of the wild-type. This result provided definitive evidence that OprH is not involved in P. aeruginosa aminoglycoside resistance and that the changes in resistance in strain H855 and a previously reported oprH mutant were due to polar effects on phoP-phoQ rather than loss of OprH expression. A role for PhoP-PhoQ in resistance to aminoglycosides is envisaged that is distinct from that in resistance to Cationic Peptides and polymyxin B.
Sibel Dosler - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Peptides: Coming to the end of antibiotic era, the most promising agents
Istanbul Journal of Pharmacy, 2017Co-Authors: Sibel DoslerAbstract:Recently, because of the rising in multidrug resistance from infectious agents, there is a prompted interest for the development of new Antimicrobial agents and new therapeutic strategies to combat the infections caused by the resistant bacteria. Among them, the natural bactericidal compounds, such as Antimicrobial Cationic Peptides (AMPs) seems very promising agents. AMPs are the important component of the innate immune response to the surrounding microorganisms. This substances which can be isolated from most of the living organisms, have various activity like broad spectrum antibacterial, antifungal, antiviral, and antiprotozoal. However there are some resistance mechanisms that affects the AMPs, because of the rapid action and existing more than one mechanism of action, development of resistance to AMPs is quite rare. Due to their many advantages and characteristics, AMPs looks like a good candidate for being a new generation, active Antimicrobial agent for Antimicrobial chemotherapy against especially multi drug resistant bacteria and biofilms, either alone or in combination.
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Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria
Journal of Chemotherapy, 2016Co-Authors: Sibel Dosler, Elif Karaaslan, Alev A GercekerAbstract:In vitro antibacterial and anti-biofilm activities of Antimicrobial Cationic Peptides (AMPs) – melittin and colistin – both alone and in combination with antibiotics were evaluated against clinical isolates of Gram-negative bacteria. Minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index were determined by the microbroth dilution and chequerboard techniques, respectively. The time-kill curve (TKC) method was used for determining the bactericidal activities of AMPs alone and in combination. Measurements of anti-biofilm activities were performed spectrophotometrically for both inhibition of attachment and 24-hour biofilm formation at MIC or subMIC. According to MIC90 values, the most active agents against Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae were colistin, imipenem and ciprofloxacin, respectively. In combination studies, synergistic effects were mostly seen with colistin–imipenem against E. coli and K. pneumoniae (50 and 54%, respectively), c...
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Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and Antimicrobial Peptides.
Peptides, 2014Co-Authors: Sibel Dosler, Elif KaraaslanAbstract:Abstract Pseudomonas aeruginosa is one of the major nosocomial pathogen that can causes a wide variety of acute and chronic infections P. aeruginosa is a dreaded bacteria not just because of the high intrinsic and acquired antibiotic resistance rates but also the biofilm formation and production of multiple virulence factors. We investigated the in vitro activities of antibiotics (ceftazidime, tobramycin, ciprofloxacin, doripenem, piperacillin and colistin) and Antimicrobial Cationic Peptides (AMPs; LL-37, CAMA: cecropin(1–7)-melittin A(2–9) amide, melittin, defensin and magainin-II) alone or in combination against biofilms of laboratory strain ATCC 27853 and 4 clinical strains of P. aeruginosa . The minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentrations (MBEC) were determined by microbroth dilution technique. The MBEC values of antibiotics and AMPs were 80–>5120 and 640–>640 mg/L, respectively. When combined with the LL-37 or CAMA at 1/10× MBEC, the MBEC values of antibiotics that active against biofilms, were decreased up to 8-fold. All of the antibiotics, and AMPs were able to inhibit the attachment of bacteria at the 1/10× MIC and biofilm formation at 1× or 1/10× MIC concentrations. Time killing curve studies showed 3-log 10 killing against biofilms in 24 h with almost all studied antibiotics and AMPs. Synergism were seen in most of the studied combinations especially CAMA/LL-37 + ciprofloxacin against at least one or two strains’ biofilms. Since biofilms are not affected the antibiotics at therapeutic concentrations, using a combination of Antimicrobial agents including AMPs, or inhibition of biofilm formation by blocking the attachment of bacteria to surfaces might be alternative methods to fight with biofilm associated infections.
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in vitro pharmacokinetics of Antimicrobial Cationic Peptides alone and in combination with antibiotics against methicillin resistant staphylococcus aureus biofilms
Peptides, 2013Co-Authors: Sibel Dosler, Emel MataraciAbstract:Abstract Antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections is becoming more difficult in hospitals and communities because of strong biofilm-forming properties and multidrug resistance. Biofilm-associated MRSA is not affected by therapeutically achievable concentrations of antibiotics. Therefore, we investigated the in vitro pharmacokinetic activities of Antimicrobial Cationic Peptides (AMPs; indolicidin, cecropin [1–7]-melittin A [2–9] amide [CAMA], and nisin), either alone or in combination with antibiotics (daptomycin, linezolid, teicoplanin, ciprofloxacin, and azithromycin), against standard and 2 clinically obtained MRSA biofilms. The minimum inhibitory concentrations (MIC) and minimum biofilm-eradication concentrations (MBEC) were determined by microbroth dilution technique. The time-kill curve (TKC) method was used to determine the bactericidal activities of the AMPs alone and in combination with the antibiotics against standard and clinically obtained MRSA biofilms. The MIC values of the AMPs and antibiotics ranged between 2 to 16 and 0.25 to 512 mg/L, and their MBEC values were 640 and 512 to 5120 mg/L, respectively. The TKC studies demonstrated that synergistic interactions occurred most frequently when using nisin + daptomycin/ciprofloxacin, indolicidin + teicoplanin, and CAMA + ciprofloxacin combinations. No antagonism was observed with any combination. AMPs appear to be good candidates for the treatment of MRSA biofilms, as they act as both enhancers of anti-biofilm activities and help to prevent or delay the emergence of resistance when used either alone or in combination with antibiotics.
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in vitro activities of antibiotics and Antimicrobial Cationic Peptides alone and in combination against methicillin resistant staphylococcus aureus biofilms
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Emel Mataraci, Sibel DoslerAbstract:Methicillin-resistant Staphylococcus aureus (MRSA) strains are most often found as hospital- and community-acquired infections. The danger of MRSA infections results from not only the emergence of multidrug resistance but also the occurrence of bacteria that form strong biofilms. We investigated the in vitro activities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin, and ciprofloxacin) and Antimicrobial Cationic Peptides {AMPs; indolicidin, CAMA [cecropin (1-7)–melittin A (2-9) amide], and nisin} alone or in combination against MRSA ATCC 43300 biofilms. The MICs and minimum biofilm eradication concentrations (MBECs) were determined by the broth microdilution technique. Antibiotic and AMP combinations were assessed using the checkerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs ranged between 0.125 and 512 and 8 and 16 mg/liter, respectively, and the MBEC values were between 512 and 5,120 and 640 mg/liter, respectively. With a fractional inhibitory concentration of ≤0.5 as the borderline, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at 1/10 MIC and biofilm formation at 1× MIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of Antimicrobial agents. Use of a combination of Antimicrobial agents can provide a synergistic effect, which rapidly enhances antibiofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.
Emel Mataraci - One of the best experts on this subject based on the ideXlab platform.
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in vitro pharmacokinetics of Antimicrobial Cationic Peptides alone and in combination with antibiotics against methicillin resistant staphylococcus aureus biofilms
Peptides, 2013Co-Authors: Sibel Dosler, Emel MataraciAbstract:Abstract Antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections is becoming more difficult in hospitals and communities because of strong biofilm-forming properties and multidrug resistance. Biofilm-associated MRSA is not affected by therapeutically achievable concentrations of antibiotics. Therefore, we investigated the in vitro pharmacokinetic activities of Antimicrobial Cationic Peptides (AMPs; indolicidin, cecropin [1–7]-melittin A [2–9] amide [CAMA], and nisin), either alone or in combination with antibiotics (daptomycin, linezolid, teicoplanin, ciprofloxacin, and azithromycin), against standard and 2 clinically obtained MRSA biofilms. The minimum inhibitory concentrations (MIC) and minimum biofilm-eradication concentrations (MBEC) were determined by microbroth dilution technique. The time-kill curve (TKC) method was used to determine the bactericidal activities of the AMPs alone and in combination with the antibiotics against standard and clinically obtained MRSA biofilms. The MIC values of the AMPs and antibiotics ranged between 2 to 16 and 0.25 to 512 mg/L, and their MBEC values were 640 and 512 to 5120 mg/L, respectively. The TKC studies demonstrated that synergistic interactions occurred most frequently when using nisin + daptomycin/ciprofloxacin, indolicidin + teicoplanin, and CAMA + ciprofloxacin combinations. No antagonism was observed with any combination. AMPs appear to be good candidates for the treatment of MRSA biofilms, as they act as both enhancers of anti-biofilm activities and help to prevent or delay the emergence of resistance when used either alone or in combination with antibiotics.
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in vitro activities of antibiotics and Antimicrobial Cationic Peptides alone and in combination against methicillin resistant staphylococcus aureus biofilms
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Emel Mataraci, Sibel DoslerAbstract:Methicillin-resistant Staphylococcus aureus (MRSA) strains are most often found as hospital- and community-acquired infections. The danger of MRSA infections results from not only the emergence of multidrug resistance but also the occurrence of bacteria that form strong biofilms. We investigated the in vitro activities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin, and ciprofloxacin) and Antimicrobial Cationic Peptides {AMPs; indolicidin, CAMA [cecropin (1-7)–melittin A (2-9) amide], and nisin} alone or in combination against MRSA ATCC 43300 biofilms. The MICs and minimum biofilm eradication concentrations (MBECs) were determined by the broth microdilution technique. Antibiotic and AMP combinations were assessed using the checkerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs ranged between 0.125 and 512 and 8 and 16 mg/liter, respectively, and the MBEC values were between 512 and 5,120 and 640 mg/liter, respectively. With a fractional inhibitory concentration of ≤0.5 as the borderline, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at 1/10 MIC and biofilm formation at 1× MIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of Antimicrobial agents. Use of a combination of Antimicrobial agents can provide a synergistic effect, which rapidly enhances antibiofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.
Jian Li - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of novel Antimicrobial Cationic Peptides nab 7061 and nab 739 in rats following intravenous administration
Journal of Antimicrobial Chemotherapy, 2009Co-Authors: Anima Poudyal, Timo Vaara, Roger L Nation, Martti Vaara, Jian LiAbstract:OBJECTIVES: To determine the disposition of novel Antimicrobial Cationic Peptides NAB 7061 and NAB 739 following intravenous administration in rats. METHODS: Sprague-Dawley rats received a single intravenous bolus of 1.0 mg/kg NAB 7061 or NAB 739. Plasma concentrations of NAB 7061 or NAB 739 were determined by HPLC or liquid chromatography-mass spectrometry. The pharmacokinetic parameters of NAB 7061 and NAB 739 were calculated using non-compartmental analysis. RESULTS: Corresponding total body clearance, volume of distribution at steady state and terminal half-life of NAB 7061 and NAB 739 averaged 3.84 and 2.63 mL/min/kg, 339 and 222 mL/kg, and 66.2 and 69.0 min, respectively. Approximately 7.16% and 19.4% of the dose was eliminated in an unchanged form via the urine in 24 h for NAB 7061 and NAB 739, respectively. CONCLUSIONS: While both compounds had generally similar pharmacokinetics to colistin, even minor alterations in the chemical structures appear to have an impact on their pharmacokinetics, especially on their clearance by the kidney. There are also substantial differences in relation to the relative contributions of renal and non-renal clearance to overall elimination from the body.
Santosh Misra - One of the best experts on this subject based on the ideXlab platform.
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Molecular and biological characterization of a severe isolate of Tomato chlorotic dwarf viroid containing a novel terminal right (TR) domain sequence
European Journal of Plant Pathology, 2009Co-Authors: Rudra P. Singh, Andrea D. Dilworth, Xiaoping Ao, Mathuresh Singh, Santosh MisraAbstract:Tomato chlorotic dwarf viroid (TCDVd) manually inoculated to transgenic (cv.‘Desiree’) potato plants containing Antimicrobial Cationic Peptides failed to develop symptoms in above ground plant parts, but infected tubers were symptomatic. Plants from the infected tubers (second generation plants) emerged as either severely stunted (bushy stunt isolate, BSI) or tall and symptomless. Molecular characterization of BSI isolates showed TCDVd sequence variants 95 to 98% identical to TCDVd sequences from the database, while a viroid variant identical to TCDVd type isolate (acc # AF162131) was cloned from symptomless plants. The TCDVd BSI variants had novel U165C, GU177-178AA, and UCAC181-184CUUU nucleotide substitutions in the terminal right (TR) domain of the viroid molecule. The cloned viroid cDNAs of the BSI were infectious to experimental (cv. ‘Sheyenne’) tomato plants causing stunted plants with profuse auxiliary shoots. Visual evaluation of the susceptibility of the BSI to 18 potato and 21 tomato cultivars revealed severe symptoms in most cultivars of both species. The progeny variants accumulating in each potato and tomato cultivar exhibited the same novel TR domain in most cultivars, with only a slight variation in a few. The severity of the stunting symptoms induced by TCDVd from BSI isolates in both potato and tomato cultivars has not been noted previously with other TCDVd isolates and, as such, it is proposed that this new isolate be recognized as a distinct genotype. Emergence of this type of sequence variant in commercial fields or commercial tomato greenhouses could potentially cause relevant losses in both crops.
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Expression of a polyphemusin variant in transgenic tobacco confers resistance against plant pathogenic bacteria, fungi and a virus
Plant Cell Tissue and Organ Culture, 2007Co-Authors: Apurva Bhargava, Milan Osusky, Benjamin S. Forward, Robert E. Hancock, Santosh MisraAbstract:Antimicrobial Cationic Peptides provide a promising means of engineering plant resistance to a range of plant pathogens, including viruses. PV5 is a synthetic structural variant of polyphemusin, a Cationic peptide derived from the horseshoe crab- Limulus polyphemus . PV5 has been shown to be benign toward eukaryotic membranes but with enhanced Antimicrobial activity against animal pathogens. In this work, the cytotoxicity of PV5 toward tobacco protoplasts and leaf discs was assessed using TTC (2,3,5-triphenyltetrazolium chloride) and Evans blue colorimetric assays. PV5 showed no measurable cytotoxic effects even at levels as high as 60 μg. As a possible approach to enhancing plant resistance, a gene encoding PV5 was fused to the signal sequence encoding the C-terminus portion of the BiP protein from Pseudotsuga menziesii , under the control of 2 × 35S CaMV promoter. When introduced into Nicotiana tabacum var Xanthi gene integration and expression was confirmed by both Southern and northern analyses. When transgenic plants were subsequently challenged with bacterial and fungal phytopathogens enhanced resistance was observed. Moreover, transgenic plants also displayed antiviral properties against Tobacco Mosaic Virus making PV5 an excellent candidate for conferring unusually broad spectrum resistance to plants and the first anti-plant virus Antimicrobial peptide.
