Abstract:
:As a consequence of blood-borne bacterial sepsis, endotoxin or lipopolysaccharide (LPS) from the cell walls of gram-negative bacteria can trigger an acute inflammatory response, leading to a series of pathological events and often resulting in death. To block this inflammatory response to endotoxin, a novel lipid A analogue, E5531, was designed and synthesized as an LPS antagonist, and its biological properties were examined in vitro and in vivo. In murine peritoneal macrophages, E5531 inhibited the release of tumor necrosis factor alpha (TNF-alpha) by Escherichia coli LPS with a 50% inhibitory concentration (IC50) of 2.2 nM, while E5531 elicited no significant increases in TNF-alpha on its own. In support of a mechanism consistent with antagonism of binding to a cell surface receptor for LPS, E5531 inhibited equilibrium binding of radioiodinated LPS ([125I]2-(r-azidosalicylamido)-1, 3'-dithiopropionate-LPS) to mouse macrophages with an IC50 of 0.50 microM. E5531 inhibited LPS-induced increases in TNF-alpha in vivo when it was coinjected with LPS into C57BL/6 mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG). In this model, the efficacy of E5531 was inversely correlated to the LPS challenge dose, consistent with a competitive antagonist-like mechanism of action. Blockade of the inflammatory response by E5531 could further be demonstrated in other in vivo models: E5531 protected BCG-primed mice from LPS-induced lethality in a dose-dependent manner and suppressed LPS-induced hepatic injury in Propionibacterium acnes-primed or galactosamine-sensitized mice. These results argue that the novel synthetic lipid A analogue E5531 can antagonize the action of LPS in in vitro and suppress the pathological effects of LPS in vivo in mice.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kobayashi S,Kawata T,Kimura A,Miyamoto K,Katayama K,Yamatsu I,Rossignol DP,Christ WJ,Kishi Ydoi
10.1128/AAC.42.11.2824subject
Has Abstractpub_date
1998-11-01 00:00:00pages
2824-9issue
11eissn
0066-4804issn
1098-6596journal_volume
42pub_type
杂志文章abstract::The antimalarial drug quinine has been shown to impair human polymorphonuclear leukocyte (PMN) functions. To gain insight into the mechanism of this phenomenon, we investigated quinine uptake by PMN with a fluorometric assay based on the fluorescence properties of this drug. After 30 min of incubation at 37 degrees C ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1474
更新日期:1991-07-01 00:00:00
abstract::beta-Lactamases produced by urine isolates from patients in long-term care facilities (LTCFs), outpatient, clinics, and one hospital in a U.S. community were characterized. A total of 1.3% of all Escherichia coli and Klebsiella pneumoniae isolates collected from patients in 30 LTCFs and various outpatient clinics prod...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00877-08
更新日期:2008-10-01 00:00:00
abstract::The minimal inhibitory concentration of temocillin (BRL 17421) against 476 clinical isolates was determined by an agar dilution method. Temocillin was active against most of the Enterobacteriaceae, Haemophilus, and Neisseria strains tested. The compound showed low activity or was inactive against Bacteroides, Campylob...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.4.535
更新日期:1982-10-01 00:00:00
abstract::In Cambodia, multidrug-resistant Plasmodium falciparum undermines the treatment of uncomplicated malaria, and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia. We conducted a single-arm, open-label, prospective study between July and December 2017 at the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02242-18
更新日期:2019-02-26 00:00:00
abstract::In 1891 Guttmann and Ehrlich (P. Guttmann and P. Ehrlich, Berlin Klin. Wochenschr. 28:953-956, 1891) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue. Si...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.12.2671
更新日期:1995-12-01 00:00:00
abstract::Pseudomonas putida is well known for its metabolic capabilities, but recently, it has been shown to exhibit resistance to a wide range of antibiotics. In P. putida DOT-T1E, the TtgABC efflux pump, which has a broad substrate specificity, extrudes antibiotics such as ampicillin, carbenicillin, tetracycline, nalidixic a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3067-3072.2003
更新日期:2003-10-01 00:00:00
abstract::Several antibiotics have disulfiram-like effects; we evaluated disulfiram for its antibiotic-like effects. Disulfiram inhibited the in vitro growth of methicillin-resistant Staphylococcus aureus, with an MIC of 1.33 micrograms/ml, but was not effective against members of the family Enterobacteriaceae or Pseudomonas sp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.4.785
更新日期:1991-04-01 00:00:00
abstract::This study analyzed the enzymatic basis and molecular epidemiology of amoxicillin-clavulanate-resistant Escherichia coli isolated by the microbiology laboratory of a United States tertiary care hospital. From October 1998 to December 1999, all E. coli isolates were screened for ampicillin-sulbactam resistance. Of 283 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1520-1525.2004
更新日期:2004-05-01 00:00:00
abstract::The bactericidal activity of the novel beta-defensin hBD-3 against 28 species and 55 strains of gram-positive cocci and gram-negative fermentative and nonfermentative rods was tested. All strains proved to be highly or intermediately susceptible to hBD-3 (minimal bactericidal concentration [MBC], =50 micro g/ml), ex...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.5.1739-1741.2003
更新日期:2003-05-01 00:00:00
abstract::Multiresistant enterococci were tested for susceptibility to trimethoprim (TMP). Although most enterococci are inhibited by less than or equal to 1.0 microgram/ml, the MICs for 7 of 29 selected multiresistant isolates were greater than or equal to 8 micrograms/ml, including for two beta-lactamase positive (Bla+) strai...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.9.1928
更新日期:1991-09-01 00:00:00
abstract::Thirty-two strains of Trichophyton rubrum and 16 strains of Trichophyton mentagrophytes isolated from patients with tinea unguium in various parts of Germany were subjected to a microdilution test with six systemic or topical antimycotic agents. Apart from griseofulvin, there were no species-specific differences betwe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/aac.39.5.1206
更新日期:1995-05-01 00:00:00
abstract::GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3168-3174.2002
更新日期:2002-10-01 00:00:00
abstract::Extended-spectrum class C β-lactamases have evolved to rapidly inactivate expanded-spectrum cephalosporins, a class of antibiotics designed to be resistant to hydrolysis by β-lactamase enzymes. To better understand the mechanism by which Acinetobacter-derived cephalosporinase-7 (ADC-7), a chromosomal AmpC enzyme, hydr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01183-20
更新日期:2020-11-17 00:00:00
abstract::Phosphorothioate oligonucleotides complementary to mRNA of the human cytomegalovirus (HCMV) DNA polymerase gene or to RNA transcripts of the major immediate-early regions 1 and 2 (IE1 and IE2) of HCMV were evaluated for antiviral activity in a 96-well immunoassay with primary human dermal fibroblasts as host cells. Ol...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.9.1945
更新日期:1993-09-01 00:00:00
abstract::The adaptive resistance of Pseudomonas aeruginosa to aminoglycosides is known to occur during chronic lung infections in cystic fibrosis patients in response to nonlethal concentrations of aminoglycosides. Not only is it difficult to achieve high levels of drug throughout the dehydrated mucus in the lung, but also ste...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00935-10
更新日期:2011-05-01 00:00:00
abstract::Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05516-11
更新日期:2012-03-01 00:00:00
abstract::The mutations in the quinolone resistance-determining region of the gyrA gene from clinical isolates of Pseudomonas aeruginosa were determined by DNA sequencing. The strains were isolated in 1989 and 1993. No mutations were detected in the clinical isolates in 1989, while five types of mutations were identified in the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.9.1970
更新日期:1995-09-01 00:00:00
abstract::The in vitro activities of eight antifungal drugs against clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested. The resulting MIC(90)s for all strains (n = 55) were as follows, in increasing order: posaconazole, 0.063 microg/ml; itraconazole, 0.125 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01655-09
更新日期:2010-04-01 00:00:00
abstract::Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.49.5.1808-1812.2005
更新日期:2005-05-01 00:00:00
abstract::The linkage between the macrolide efflux gene mef(I) and the chloramphenicol inactivation gene catQ was first described in Streptococcus pneumoniae (strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different defective IQ elements were detected in Streptococcus pyogen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03638-14
更新日期:2014-10-01 00:00:00
abstract::Mice treated with antibiotics early or late after active infection had resolved were examined for chlamydial DNA in endocervical swabs. The early eradication of infection limited oviduct pathology, despite the continued detection of chlamydial DNA by nested PCR. Late antibiotic treatment had no effect on the ability t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00231-07
更新日期:2007-07-01 00:00:00
abstract::The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01870-15
更新日期:2015-12-14 00:00:00
abstract::The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patien...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03796-14
更新日期:2014-12-01 00:00:00
abstract::Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy. Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.1.56
更新日期:1992-01-01 00:00:00
abstract::The transfer of DNA between Enterococcus faecium strains has been characterized both by the movement of well-defined genetic elements and by the large-scale transfer of genomic DNA fragments. In this work, we report on the whole-genome analysis of transconjugants resulting from mating events between the vancomycin-res...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00488-16
更新日期:2016-09-23 00:00:00
abstract::Bacillus subtilis strain 168 produces the extremely stable and broad-spectrum lantibiotic sublancin 168. Known sublancin 168-susceptible organisms include important pathogens, such as Staphylococcus aureus. Nevertheless, since its discovery, the mode of action of sublancin 168 has remained elusive. The present studies...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00439-09
更新日期:2009-11-01 00:00:00
abstract::Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl-D-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of us...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1076
更新日期:1998-05-01 00:00:00
abstract::Bovicin HC5, a broad-spectrum lantibiotic produced by Streptococcus bovis HC5, catalyzed the efflux of intracellular potassium from Streptococcus bovis JB1, a sensitive strain. The level of ATP also decreased, but this decline appeared to be caused by the activity of the F(1)F(0) ATPase rather than efflux per se. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00109-08
更新日期:2008-06-01 00:00:00
abstract::The dose dependence of mezlocillin pharmacokinetics was examined in relation to renal function after intravenous doses of 1 and 5 g in 16 subjects with various degrees of renal impairment. Dose and time-average model-independent physiological parameters were calculated from plasma concentration and urinary excretion d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.428
更新日期:1982-03-01 00:00:00
abstract::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.971
更新日期:1990-06-01 00:00:00