Abstract:
:To study the antimalarial action of chloroquine, normal mouse erythrocytes were used as surrogates for erythrocytoid bodies. These bodies form in the endosomes of intraerythrocytic malaria parasites as they feed on their host and consist of erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In suspensions of normal erythrocytes or lysates (equivalent to 5 microl of erythrocytes per ml in each case), hemoglobin underwent denaturation when it was incubated at 38 degrees C in 150 mM sodium acetate (pH 5). It is reasonable to assume that the same phenomenon occurs in acidic endosomes. Addition of 100 microM chloroquine to the incubation mixture caused the rate of hemoglobin denaturation to double to 40 nanomoles per hour per ml of packed erythrocytes. This effect required the presence of erythrocyte stroma and was inhibited by reducing the temperature to 24 degrees C or increasing the pH to 6. We propose that the primary antimalarial action of chloroquine is to bind to ferriprotoporphyrin IX (FP) and remove it from oxidized hemoglobin, thus producing toxic FP-chloroquine complexes and an excess of denatured globin. Furthermore, we suggest that these substances inhibit endosomal maturation and thereby cause hemoglobin accumulation in immature endosomes and masking of the lipids needed for FP dimerization. The term "masking" is used to signify that unsaturated lipids are present in parasitized erythrocytes but are specifically unavailable to promote FP dimerization.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Fitch CD,Russell NVdoi
10.1128/AAC.01652-05subject
Has Abstractpub_date
2006-07-01 00:00:00pages
2415-9issue
7eissn
0066-4804issn
1098-6596pii
50/7/2415journal_volume
50pub_type
杂志文章abstract::The anti-hepatitis C virus nucleotide prodrug GS-6620 employs a double-prodrug approach, with l-alanine-isopropyl ester and phenol moieties attached to the 5'-phosphate that release the nucleoside monophosphate in hepatocytes and a 3'-isobutyryl ester added to improve permeability and oral bioavailability. Consistent ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02350-13
更新日期:2014-01-01 00:00:00
abstract::Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00009-13
更新日期:2013-06-01 00:00:00
abstract::Resistance-nodulation-division (RND) efflux pumps are important contributors to bacterial antibiotic resistance. In this study, we combined evolutionary sequence analyses, computational structural modeling, and ligand docking to develop a framework that can explain the known antibiotic substrate selectivity difference...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00496-20
更新日期:2020-07-22 00:00:00
abstract::Retrospective analysis of 189 nonredundant strains of Pseudomonas aeruginosa sequentially recovered from the sputum samples of 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out of 189 (28%) samples were hypersusceptible to the beta-lactam antibiotic ticarcillin (MIC < or = 4 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01024-08
更新日期:2009-05-01 00:00:00
abstract::Two genes (rpsL and rrs) with mutations associated with streptomycin resistance in Mycobacterium tuberculosis were characterized in 78 streptomycin-resistant and 61 streptomycin-susceptible isolates recovered from patients living in the United States, South America, Europe, Africa, and Asia. Fifty-four percent of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.1024
更新日期:1996-04-01 00:00:00
abstract::Two hundred clinical isolates of Haemophilus influenzae were tested for tolerance (MBC/MIC greater than or equal to 32) to ampicillin and cefotaxime by broth dilution tests. Of 200 strains, 9 were tolerant to ampicillin, and 10 were tolerant to cefotaxime. Tolerant organisms were identified in both systemic and nonsys...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.2.320
更新日期:1985-08-01 00:00:00
abstract::We assessed prophylactic or continuous therapy of isavuconazole, posaconazole, or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02589-16
更新日期:2017-04-24 00:00:00
abstract::Despite controversies associated with forms and value of antibiotic therapy for cystic fibrosis patients, antibiotherapy remains a cornerstone in the management of those patients. Locally administered liposome-encapsulated antibiotics may offer advantages over free antibiotics, including sustained concentration of the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.3.665
更新日期:1996-03-01 00:00:00
abstract::With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02223-16
更新日期:2017-06-27 00:00:00
abstract::The ability of novobiocin to eliminate (cure) the wild-type plasmid pMG110 from Escherichia coli has been compared with that of other inhibitors of the gyrase B subunit and of the gyrase A subunit. Novobiocin eliminated pMG110 , producing over 99% plasmid loss at concentrations two- to eightfold below the MIC for bact...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.5.586
更新日期:1984-05-01 00:00:00
abstract::Mycograb (NeuTec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemother...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2208-2216.2003
更新日期:2003-07-01 00:00:00
abstract::All known DNA ligases catalyze the formation of a phosphodiester linkage between adjacent termini in double-stranded DNA via very similar mechanisms. The ligase family can, however, be divided into two classes: eubacterial ligases, which require NAD(+) as a cofactor, and other ligases, from viruses, archaea, and eukar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.11.2766
更新日期:1999-11-01 00:00:00
abstract::Hand-foot-and-mouth disease (HFMD), caused by enterovirus, is a threat to public health worldwide. To date, enterovirus 71 (EV71) has been one of the major causative agents of HFMD in the Pacific-Asia region, and outbreaks with EV71 cause millions of infections. However, no drug is currently available for clinical the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00298-17
更新日期:2017-06-27 00:00:00
abstract::The in vitro activities of four fluoroquinolone compounds were tested against 92 Escherichia coli strains of ovine and caprine origin under aerobic and anaerobic incubation conditions. The four fluoroquinolones proved to be highly effective against the E. coli isolates tested. When bacteria were cultured anaerobically...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.10.2469
更新日期:1994-10-01 00:00:00
abstract::Macrolides are the antimicrobials of choice for treating human campylobacteriosis. The recent emergence of erm(B) in Campylobacter bacteria threatens the utility of this class of antibiotics. Here we report the constitutive and inducible expression of erm(B) in Campylobacter isolates derived from diarrheal patients an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01103-15
更新日期:2015-10-01 00:00:00
abstract::In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of Acinetobacter baumannii was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned abeS gene in hypersensitive Escherichia coli host KAM32 resulted in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00748-09
更新日期:2009-12-01 00:00:00
abstract::In the course of surveying for the carbapenem-hydrolyzing metallo-beta-lactamase gene bla(IMP) in pathogenic bacteria by the PCR method, we detected a gene encoding a variant metallo-beta-lactamase, designated IMP-3, which differed from IMP-1 by having low hydrolyzing activity for penicillins and carbapenems. PCR prod...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.8.2023-2027.2000
更新日期:2000-08-01 00:00:00
abstract::The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.6.1520
更新日期:1996-06-01 00:00:00
abstract::A total of 191 soil samples from Hangzhou, China, were submitted to detect non-wild-type (non-WT) Aspergillus fumigatus and its associated mechanisms. There were 2 (4.7%), 13 (12.4%), and 31 (23.1%) isolates identified as non-WT in 2014, 2016, and 2018, respectively. The resistant mutations of TR34/L98H, TR46/Y121F/T2...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00904-20
更新日期:2020-09-21 00:00:00
abstract::The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.7.5.672
更新日期:1975-05-01 00:00:00
abstract::We isolated mutant YM644, which showed elevated resistance to norfloxacin, ethidium bromide, acriflavine, and rhodamine 6G, from Pseudomonas aeruginosa YM64, a strain that lacks four major multidrug efflux pumps. The genes responsible for the resistance were mexHI-opmD. Elevated ethidium extrusion was observed with ce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.9.2990-2992.2003
更新日期:2003-09-01 00:00:00
abstract::Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.7
更新日期:1979-01-01 00:00:00
abstract::The 72 Escherichia coli strains of the ECOR collection were examined for resistance to 10 different antimicrobial agents including ampicillin, tetracycline, mercury, trimethoprim, and sulfonamides. Eighteen strains were resistant to at least one of the antibiotics tested, and nearly 20% (14 of 72) were resistant to tw...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1568-1574.2000
更新日期:2000-06-01 00:00:00
abstract::We previously reported the development of a prototype antibiotic sensitivity assay to detect drug-resistant Mycobacterium tuberculosis using infection by mycobacteriophage to create a novel nucleic acid transcript, a surrogate marker of mycobacterial viability, detected by reverse transcriptase PCR (M. C. Mulvey et al...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03135-14
更新日期:2015-01-01 00:00:00
abstract::Previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. In this study, we used timcodar (formerly VX-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-TB) drugs against Mycobacterium tuberculosis in in vitro and in vivo combination st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04271-14
更新日期:2015-03-01 00:00:00
abstract::Caspofungin (CAS) is approved for second-line management of proven or probable invasive aspergillosis at a dose of 50 mg once daily (QD). Preclinical and limited clinical data support the concept of the dose-dependent antifungal efficacy of CAS with preservation of its favorable safety profile. Little is known, howeve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01912-12
更新日期:2013-04-01 00:00:00
abstract::Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster-containing proteins commonly encountered in anaerobic prokaryotes. However, with the exception of Isf from Methanosarcina thermophila, which participates in oxidative stress management by removing oxygen and hydrogen peroxide, none of the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02320-13
更新日期:2014-06-01 00:00:00
abstract::The topical delivery of liposomally encapsulated interferon was evaluated in the cutaneous herpes simplex virus guinea pig model. Application of liposomally entrapped interferon caused a reduction of lesion scores, whereas application of interferon formulated as a solution or as an emulsion was ineffective. The method...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.8.1217
更新日期:1989-08-01 00:00:00
abstract::A clinical isolate of Bacteroides vulgatus was resistant to tetracycline, clindamycin, ampicillin, cephaloridine, cefoxitin, and other beta-lactam antibiotics except imipenem. beta-Lactam resistance was mediated by a membrane-associated, clavulanate-sensitive cephalosporinase capable of degrading cephalosporins and pe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.5.1028
更新日期:1993-05-01 00:00:00
abstract::Antagonism of antibiotic activity by peritoneal dialysate has been postulated to be a cause of failure of treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. We evaluated by a case-control study whether unexpected treatment failure could be attributed to such antagonism. Bacteria isolated ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.5.1097
更新日期:1992-05-01 00:00:00