Abstract:
:The 13-residue dermaseptin S4 derivative K(4)S4(1-13)a (P) was previously shown to kill intraerythrocytic malaria parasites through the lysis of the host cells. In this study, we have sought peptides that will kill the parasite without lysing the erythrocyte. To produce such peptides, 26 compounds of variable structure and size were attached to the N terminus of P and screened for antiplasmodium and hemolytic activities in cultures of Plasmodium falciparum. Results from this screen indicated that increased hydrophobicity results in amplified antiplasmodium effect, irrespective of the linearity or bulkiness of the additive. However, increased hydrophobicity also was generally associated with increased hemolysis, with the exception of two derivatives: propionyl-P (C3-P) and isobutyryl-P (iC4-P). Both acyl-peptides were more effective than P, with 50% growth inhibition at 3.8, 4.3, and 7.7 microM, respectively. The antiparasitic effect was time dependent and totally irreversible, implying a cytotoxic effect. The peptides were also investigated in parallel for their ability to inhibit parasite growth and to induce hemolysis in infected and uninfected erythrocytes. Whereas the dose dependence of growth inhibition and hemolysis of infected cells overlapped when cells were treated with P, the acyl-peptides exerted 50% growth inhibition at concentrations that did not cause hemolysis. Noticeably, the acyl derivatives, but not P, were able to dissipate the parasite plasma membrane potential and cause depletion of intraparasite potassium under nonhemolytic conditions. These results clearly demonstrate that the acyl-peptides can affect parasite viability in a manner that is dissociated from lysis of the host cell. Overall, the data indicate the potential usefulness of this strategy for development of selective peptides as investigative tools and eventually as antimalarial agents.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Dagan A,Efron L,Gaidukov L,Mor A,Ginsburg Hdoi
10.1128/aac.46.4.1059-1066.2002subject
Has Abstractpub_date
2002-04-01 00:00:00pages
1059-66issue
4eissn
0066-4804issn
1098-6596journal_volume
46pub_type
杂志文章abstract::Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.40.3.776
更新日期:1996-03-01 00:00:00
abstract::We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microd...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.10.1880
更新日期:1990-10-01 00:00:00
abstract::Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate airway disinfection for pulmonary tuberculosis patients treated with standard therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.1209-1212.2005
更新日期:2005-03-01 00:00:00
abstract::Escherichia coli bearing a cryptic tetracycline resistance determinant from Bacteroides fragilis expressed low-level constitutive resistance to tetracycline under aerobic, but not anaerobic, growth conditions and accumulated less tetracycline aerobically than did isogenic susceptible cells. This decreased uptake was e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1739
更新日期:1987-11-01 00:00:00
abstract::Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute Plasmodium vivax malaria, which is the first new treatment in almost 60 years. A population pharmacokinetic (POP PK) analysis was conducted with tafenoquine exposure ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00711-18
更新日期:2018-10-24 00:00:00
abstract::Maribavir (1263W94, VP-41263) is an oral anticytomegalovirus agent under clinical development. The pharmacokinetics and safety of maribavir and the effects of maribavir on the activities of cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) were eval...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.50.4.1130-1135.2006
更新日期:2006-04-01 00:00:00
abstract::A double-site enzyme-linked lactate dehydrogenase enzyme immunodetection assay was tested against field isolates of Plasmodium falciparum for assessing in vitro drug susceptibilities to a wide range of antimalarial drugs. Its sensitivity allowed the use of parasite densities as low as 200 parasites/microl of blood. Be...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.4.1426-1429.2004
更新日期:2004-04-01 00:00:00
abstract::Population distributions and quality control data for strains of Pseudomonas aeruginosa tested for gentamicin susceptibility on six lots of Mueller-Hinton agar were analyzed. The lots of agar were used in three University of Washington hospitals from April 1975 through October 1977. The analyses indicated that the per...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.3.360
更新日期:1978-09-01 00:00:00
abstract::The nature of the SHV-1 beta-lactamase gene was analyzed in 97 epidemiologically unrelated Klebsiella pneumoniae strains isolated from clinical samples. beta-Lactamase bands that focused at a pI of 7.6 (SHV-1-type) in 74 strains, at a pI of 7.1 (LEN-1-type) in 13 strains, and at a pI of 5.4 (TEM-1-type) in 10 strains ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.10.2856-2861.2001
更新日期:2001-10-01 00:00:00
abstract::Desferrioxamine, a safe and effective iron chelator, was evaluated for its antibacterial and antifungal activity. The susceptibilities of 124 urinary tract isolates and 28 clinical isolates of Neisseria gonorrhoeae to desferrioxamine concentrations that are readily achievable in urine were determined. Of all isolates,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.3.375
更新日期:1984-03-01 00:00:00
abstract::Mycobacterium abscessus is intrinsically resistant to many antimycobacterial antibiotics, which presents serious problems in therapy. Here, we describe the development of a novel phenotype-based microscopic and computerized imaging drug screening approach. A pilot screen of 568 compounds from two libraries identified ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00828-18
更新日期:2018-08-27 00:00:00
abstract::Of five parenteral cephalosporins tested against 43 lactobacilli, cephaloridine, cefazolin, and cefamandole were the most active inhibitory and bactericidal agents. Timed-kill analysis revealed a slow bactericidal effect, with significant declines in mean minimal bactericidal concentration values at 48 h versus 24 h. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.1.112
更新日期:1979-07-01 00:00:00
abstract::A series of 1-cyclopropyl-8-methoxy-quinazoline-2,4-diones was synthesized and evaluated for lowering the ratio of the antimicrobial MIC in gyrase resistance mutants to that in the gyr(+) (wild type) using isogenic strains of Escherichia coli. Dione features that lowered this ratio were a 3-amino group and C-7 ring st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00330-08
更新日期:2008-11-01 00:00:00
abstract::Structural analysis of two new beta-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and alpha-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.1.3.242
更新日期:1972-03-01 00:00:00
abstract::Acquiring iron (Fe) is critical to the metabolism and growth of Mycobacterium tuberculosis. Disruption of Fe metabolism is a potential approach for novel antituberculous therapy. Gallium (Ga) has many similarities to Fe. Biological systems are often unable to distinguish Ga(3+) from Fe(3+). Unlike Fe(3+), Ga(3+) canno...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01543-13
更新日期:2013-12-01 00:00:00
abstract::We report a microanalytical high-performance liquid chromatography method for quantitation of cefpirome (HR 810) from serum. The drug was extracted from 0.05 ml of serum with 0.2 ml of isopropanol containing beta-hydroxypropyltheophylline, the internal standard. Separations were performed on a C18 column at ambient te...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.10.1481
更新日期:1988-10-01 00:00:00
abstract::Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00845-19
更新日期:2019-09-23 00:00:00
abstract::We conducted a randomized controlled trial of orally administered amifloxacin versus trimethoprimsulfamethoxazole (TMP-SMX) as treatments of acute uncomplicated urinary tract infection in women. Amifloxacin at a dosage of 200 mg twice a day appeared as safe and effective as TMP-SMX, but amifloxacin at 400 mg twice a d...
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.34.4.665
更新日期:1990-04-01 00:00:00
abstract::The bla(TLA-1) gene encoding an extended-spectrum beta-lactamase was identified in 11 enterobacterial isolates from Mexico City, Mexico. This gene was located on different plasmids and plasmid types with different sizes and incompatibility groups. It was associated with a novel insertion sequence, ISCR20, encoding a p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00075-10
更新日期:2010-09-01 00:00:00
abstract::TBR-652 is a novel CCR5 antagonist with potent in vitro anti-HIV activity. The objective of this study was to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of TBR-652 in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients. A double-blind, placebo-controlled, randomized,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00713-10
更新日期:2011-06-01 00:00:00
abstract::The antiviral activity of zinc salts against rhinovirus types 1A and 39 was assayed by yield reduction and inhibition of cytopathic effect in cell culture. The findings indicate that the zinc salts tested have low in vitro therapeutic indices and suggest that the possible beneficial effects of zinc lozenges in reducin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.4.622
更新日期:1987-04-01 00:00:00
abstract::The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3'-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00659-13
更新日期:2013-08-01 00:00:00
abstract::The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.2.418
更新日期:1999-02-01 00:00:00
abstract::Moderately penicillin-resistant Neisseria meningitidis was responsible for an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada in 1993. We tested fully susceptible and moderately resistant strains of N. meningitidis against ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, penicillin, and ri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.11.2577
更新日期:1995-11-01 00:00:00
abstract::Ninety-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive topical therapy for 5 days with either alpha-2a interferon at 30 X 10(6) IU/ml or 10 X 10(6) IU/ml or placebo six times daily. No differences were noted between either interferon dose and placebo with respect to ...
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.31.7.1137
更新日期:1987-07-01 00:00:00
abstract::Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.03246-14
更新日期:2014-11-01 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::Although acetylsalicylic acid does not itself induce interferon, acetylsalicylic acid was found to significantly enhance the production of both human alpha interferon and human gamma interferon when added with the appropriate inducers to cultures of human peripheral blood mononuclear cells. The mechanisms associated w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.1.114
更新日期:1987-01-01 00:00:00
abstract::Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation, and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00469-20
更新日期:2020-06-23 00:00:00
abstract::Expression of high-level beta-lactam resistance is known to be thermosensitive in many methicillin-resistant Staphylococcus aureus (MRSA) strains, including strain COL, in which the high methicillin MIC for cultures grown at 37 degrees C (800 microg/ml) was reduced to 12 microg/ml at 42 degrees C. COL grew faster at 4...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00504-07
更新日期:2008-02-01 00:00:00