Abstract:
:Early studies of immobilized peptides mainly focused upon the relationship between structural properties and the activity of soluble and surface-tethered sequences. The intention of this study was to analyze the influence of immobilization parameters upon the activity profile of peptides. Resin beads (TentaGel S NH(2), HypoGel 400 NH(2), and HypoGel 200 NH(2)) with polyethylene glycol spacers of different lengths were rendered antimicrobial by linkage of an amphipathic model KLAL peptide and magainin-derived MK5E. Standard solid-phase peptide synthesis, thioalkylation, and ligation strategies were used to immobilize the peptides at the C and N termini and via different side-chain positions. Depending upon the resin capacity and the coupling strategies, peptide loading ranged between 0.1 and 0.25 micromol/mg for C-terminally and around 0.03 micromol/mg for N-terminally and side-chain-immobilized peptides. Tethering conserved the activity spectra of the soluble peptides at reduced concentrations. The resin-bound peptides were antimicrobial toward Escherichia coli and Bacillus subtilis in the millimolar range compared to the results seen with micromolar concentrations of the free peptides. B. subtilis was more susceptible than E. coli. The antimicrobial activity distinctly decreased with reduction of the spacer length. Slight differences in the antimicrobial effect of KLAL and MK5E bound at different chain positions on TentaGel S NH(2) suggest that the activity is less dependent upon the position of immobilization. Soluble KLAL was active toward red blood cells, whereas MK5E was nonhemolytic at up to about 400 microM. Resin-induced hemolysis hampered the determination of the hemolytic effect of the immobilized peptides. TentaGel S NH(2)-bound peptides enhanced the permeability of the POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline) and mixed POPC/1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPC/POPG) bilayers used to model the charge properties of the biological targets. The results suggest that surface immobilization of the cationic amphipathic antimicrobial peptides does not influence the membrane-permeabilizing mode of action. Peptide insertion into the target membrane and likely the exchange of membrane-stabilizing bivalent cations contribute to the antimicrobial effect. In conclusion, reasonable antimicrobial activity of surface-bound peptides requires the optimization of the coupling parameters, with the length of the spacer and the amount of target-accessible peptide being the most important factors.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bagheri M,Beyermann M,Dathe Mdoi
10.1128/AAC.01254-08subject
Has Abstractpub_date
2009-03-01 00:00:00pages
1132-41issue
3eissn
0066-4804issn
1098-6596pii
AAC.01254-08journal_volume
53pub_type
杂志文章abstract::Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human volunteers was studied in order to clarify the differences in pharmacokinetic behavior between the epimers. Stereospecific high-performance liquid chromatography was used for the determination of SBPC epimers. Plasma protein binding was measu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of daptomycin for S. aureus using in vitro methods and the Craig (W. A. Craig, J. Redington, and S. C. Ebert, J. Antimicrob. Chemot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.3.845-851.2001
更新日期:2001-03-01 00:00:00
abstract::Histoplasmosis is a severe infection that affects millions of patients worldwide and is endemic in the Americas. Amphotericin B (AMB) and itraconazole are highly effective for the treatment of severe and milder forms of the disease, but AMB is toxic, and the bioavailability of itraconazole is erratic. Therefore, it is...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01654-13
更新日期:2014-05-01 00:00:00
abstract::Using an isogenic system, we have determined the impact that the four promoters known to control bla(TEM) gene expression have on beta-lactamase activity. For both TEM-1 and TEM-30, this activity gradually increased in relation to the presence of promoters P3, Pa/Pb, and P4 upstream of the corresponding gene. Promoter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.12.4035-4037.2002
更新日期:2002-12-01 00:00:00
abstract::Although often dismissed as contaminants when isolated from blood cultures, Bacillus spp. are increasingly recognized as capable of causing serious systemic infections. As part of a clinical-microbiological study, 89 strains of Bacillus spp. isolated from clinical blood cultures between 1981 and 1985 had their species...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.5.642
更新日期:1988-05-01 00:00:00
abstract::TEM-28 (pI 6.1), expressed by an Escherichia coli clinical isolate, is a novel beta-lactamase which hydrolyzed ceftazidime, cefotaxime, and aztreonam with rates of 25, 1.1, and 5.6, respectively, relative to that for benzylpenicillin (100). The nucleotide sequence of blaTEM-28 differed from that of blaTEM-1 by two bas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.1.260
更新日期:1996-01-01 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::Preclinical animal models informing antimalarial drug development are scarce. We have used asexual erythrocytic Plasmodium cynomolgi infections of rhesus macaques to model Plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. Using this malaria model, we accumulated da...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00576-08
更新日期:2009-02-01 00:00:00
abstract::We report the capacity of copper oxide-containing filters to reduce infectious titers of a panel of viruses spiked into culture media. Enveloped, nonenveloped, RNA, and DNA viruses were affected, suggesting the possibility of using copper oxide-containing devices to deactivate a wide spectrum of infectious viruses fou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00125-07
更新日期:2007-07-01 00:00:00
abstract::Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual vir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.5.690
更新日期:1978-11-01 00:00:00
abstract::The efficacy of an itraconazole-cyclodextrin solution against Aspergillus fumigatus was assessed in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis and compared with that of amphotericin B. Oral itraconazole solution at dosages of 20 and 40 mg/kg/day improved survival as compared wit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.11.2307
更新日期:1993-11-01 00:00:00
abstract::As an obligate aerobe, Mycobacterium tuberculosis uses its electron transport chain (ETC) to produce energy via oxidative phosphorylation. This pathway has recently garnered a lot of attention and is a target for several new antimycobacterials. We tested the respiratory adaptation of M. tuberculosis to phenoxyalkylben...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01677-17
更新日期:2017-12-21 00:00:00
abstract::Stenotrophomonas maltophilia is a multidrug-resistant organism increasingly isolated from the lungs of cystic fibrosis (CF) patients. One hundred twenty-five S. maltophilia isolates from 85 CF patients underwent planktonic and biofilm susceptibility testing against 9 different antibiotics, alone and in double antibiot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02215-12
更新日期:2013-03-01 00:00:00
abstract::The 2-amino-5-halo-pyrimidinones, which are potent interferon inducers and antiviral agents, were found to be protective against lethal cytomegalovirus (CMV) challenge in weanling or neonatal mice when administered before virus challenge. This protection was dependent upon the dosage of pyrimidinone administered. Wean...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.4.485
更新日期:1985-10-01 00:00:00
abstract::Moxalactam (LY127935) exhibited greater in vitro activity than cefamandole and tobramycin against clinical isolates of Enterobacteriaceae, Aeromonas hydrophila, and Pseudomonas maltophilia. The activities of the three drugs against other microorganisms were as follows: for staphylococci, cefamandole = tobramycin great...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.4.750
更新日期:1980-04-01 00:00:00
abstract::Ten strains each of 18 clinically important species of Clostridium were tested for susceptibility to clindamycin. Of the 180 strains tested, 56 (31%) were resistant to more than 1.6 mug/ml. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.136
更新日期:1973-01-01 00:00:00
abstract::Significant increases in the MIC(90)s of linezolid in multidrug-resistant Mycobacterium tuberculosis isolates were seen between the baseline period of 2001 to 2003 (0.5 microg/ml) and 2004 (2 microg/ml). The MICs were 4 microg/ml in three strains. Both fluoroquinolones (except levofloxacin) and kanamycin were found to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00414-07
更新日期:2008-06-01 00:00:00
abstract::We assessed cutaneous ethanol (ETOH) and isopropanol (ISOP) absorption after intensive (30 times per h) use of alcohol-based hand-rub solutions by healthcare workers (HCWs). ETOH was detectable in the breath of 6/20 HCWs (0.001 to 0.0025%) at 1 to 2 min postexposure and in the serum of 2/20 HCWs at 5 to 7 min postexpo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01320-06
更新日期:2007-03-01 00:00:00
abstract::The in vitro activities of extracts of Nigerian chewing sticks against Bacteroides gingivalis and B. melaninogenicus are presented. The greatest inhibitory action was produced by Serindeia werneckei, whereas Fagara zanthoxyloides produced no appreciable inhibitory effect. A generally good correlation was found between...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.4.598
更新日期:1988-04-01 00:00:00
abstract::Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.45.2.525-531.2001
更新日期:2001-02-01 00:00:00
abstract::The effects of ceftizoxime and gentamicin alone and in combination were determined against 100 Pseudomonas aeruginosa strains. Concentrations of 32 micrograms of ceftizoxime and 8 micrograms of gentamicin per ml inhibited 22 and 43% of the strains, respectively. At concentrations of ceftizoxime and gentamicin that are...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.6.770
更新日期:1984-06-01 00:00:00
abstract::Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.4.675
更新日期:1976-04-01 00:00:00
abstract::In vitro selection of mutants with decreased susceptibility to ertapenem was performed using Escherichia coli and Klebsiella pneumoniae clinical strains producing either the bla(CTX-M-2), bla(CTX-M-3), bla(CTX-M-9), or bla(CTX-M-15) gene. Frequencies of mutants with decreased susceptibilities to ertapenem were similar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01007-08
更新日期:2009-02-01 00:00:00
abstract::The in vitro susceptibilities of Actinobacillus actinomycetemcomitans to 14 antimicrobial combinations were studied by using the checkerboard titration technique. The results, expressed as the range of the fractional inhibitory concentration indices, were as follows: for metronidazole or its hydroxymetabolite combined...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2634
更新日期:1992-12-01 00:00:00
abstract::Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02109-15
更新日期:2016-03-25 00:00:00
abstract::The experimental model of infected fibrin clots in rabbits was used to study the penetration and in vivo activity of cefixime against Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The respective MICs of cefixime against these strains were 0.25, 2, and 8 micrograms/ml. The clots were infected with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.913
更新日期:1986-12-01 00:00:00
abstract::The effects of cefodizime and cefuroxime on neutrophil phagocytosis and reactive oxygen production in 54 patients undergoing elective coronary artery bypass grafting were studied. Both drugs were administered twice at a dosage of 40 mg/kg of body weight (pre- and intraoperative). Phagocytic capacity was assessed by me...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.41.7.1584
更新日期:1997-07-01 00:00:00
abstract::Clinical isolates of the Bacteroides melaninogenicus and Bacteroides fragilis groups were tested for in vitro and in vivo susceptibility to penicillin, clindamycin, and metronidazole, used singly or in combination with gentamicin. The in vitro tests consisted of determinations of minimal inhibitory concentrations (MIC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.1.71
更新日期:1984-01-01 00:00:00
abstract::The interaction of miltefosine with amphotericin B, sodium stibogluconate, paromomycin, and sitamaquine was assessed in vitro and additionally for the first three combinations in vivo. In vitro interactions were indifferent for miltefosine combined with amphotericin B (mean sums of fractional inhibitory concentrations...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.1.73-79.2006
更新日期:2006-01-01 00:00:00
abstract::There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have no...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01763-16
更新日期:2016-12-27 00:00:00