Abstract:
:The respiratory syncytial virus (RSV) L protein is a viral RNA-dependent RNA polymerase that contains multiple enzyme activities required for RSV replication. The RSV L inhibitors described in literature are limited by their cytotoxicity or the lack of RSV B subtype coverage. Here, we characterize a new RSV L inhibitor with strong antiviral activity against both RSV A and B subtypes and no detectable cytotoxicity. This compound, AZ-27, was equally active against RSV live viruses and subgenomic replicons and demonstrated advantages over other classes of RSV inhibitors in time-of-addition and cell line dependency studies. Resistance studies identified a dominant mutation in the putative capping enzyme domain of L protein, which conferred strong resistance to the AZ-27 series but not other classes of RSV inhibitors, supporting RSV L protein as the direct target for AZ-27. This novel and broad-spectrum RSV L polymerase inhibitor may pave the way toward an efficacious RSV therapeutic and provide a new tool for interrogation of the L protein function.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Tiong-Yip CL,Aschenbrenner L,Johnson KD,McLaughlin RE,Fan J,Challa S,Xiong H,Yu Qdoi
10.1128/AAC.02540-14subject
Has Abstractpub_date
2014-07-01 00:00:00pages
3867-73issue
7eissn
0066-4804issn
1098-6596pii
AAC.02540-14journal_volume
58pub_type
杂志文章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::GV129606 is a new parenteral trinem antibiotic belonging to the beta-lactam class. It combines broad-spectrum activity (against gram-negative and -positive bacteria, aerobes and anaerobes), with high potency and resistance to beta-lactamases. Comparative in vitro and in vivo antibacterial activities were determined fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.12.2742
更新日期:1997-12-01 00:00:00
abstract::The standard disk diffusion method of Bauer et al. (Am. J. Clin. Pathol. 45:493-496, 1966; National Committee for Clinical Laboratory Standards, Performance standards for antimicrobial disc susceptibility tests, approved standard ASM-2, 2nd ed., 1979) was used to monitor the potency of 16 Autobac antibiotic elution di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.516
更新日期:1982-03-01 00:00:00
abstract::The aminoglycoside-modifying enzymes present in the first 120 clinical isolates harboring extended-spectrum beta-lactamases isolated in Spain were studied. Most of these isolates (84%) were gentamicin resistant. The enzymes most frequently associated and cotransferred with SHV-2 or TEM-type beta-lactamases were AAC(3)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.11.2536
更新日期:1992-11-01 00:00:00
abstract::The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00873-16
更新日期:2016-09-23 00:00:00
abstract::We recently reported the chromosomal location of the staphylococcal beta-lactamase gene in four strains of Enterococcus faecalis. Transfer of this gene from strain CH19 to an enterococcal recipient was accompanied by transfer of numerous other antimicrobial resistance determinants in the absence of detectable plasmid ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.9.1843
更新日期:1992-09-01 00:00:00
abstract::Increases in community-acquired infections caused by extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae have important implications for hospital infection control and empirical antibiotic therapy protocols. We developed and validated a tool for identifying patients harboring these organisms at hospital ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00009-11
更新日期:2011-07-01 00:00:00
abstract::Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have in vitro activity against Mycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patie...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01101-15
更新日期:2015-09-01 00:00:00
abstract::Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00744-18
更新日期:2018-07-27 00:00:00
abstract::This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.3.247
更新日期:1979-09-01 00:00:00
abstract::Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.61
更新日期:1995-01-01 00:00:00
abstract::While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01556-18
更新日期:2019-01-29 00:00:00
abstract::Two clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae were noted to be less susceptible than expected to imipenem. Both were missing outer membrane proteins that serve as channels for antibiotic entry. The role of beta-lactamase in resistance was investigated by eliminating t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.7.1669
更新日期:1999-07-01 00:00:00
abstract::Several non-beta-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.3.961-969.2004
更新日期:2004-03-01 00:00:00
abstract::The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism. In this study, we sequenced the ampD wild type and three mutant genes of Enterobacter cloacae and Citrobacter freundii. They exhibited a high degree of homology wi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.224
更新日期:1993-02-01 00:00:00
abstract::The comparative activities of azithromycin (AZI) and clarithromycin (CLA) against eight Mycobacterium avium complex (MAC) isolates were evaluated in the beige mouse model of disseminated infection. Mice were infected intravenously with approximately 10(7) viable MAC isolate. AZI at 100 or 200 mg/kg of body weight or C...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1452
更新日期:1994-07-01 00:00:00
abstract::Respiratory infection with Burkholderia cenocepacia is associated with accelerated decline in lung function and increased mortality in cystic fibrosis (CF) patients (A. M. Jones, M. E. Dodd, J. R. W. Govan, V. Barcus, C. J. Doherty, J. Morris, and A. K. Webb, Thorax 59:948-951, 2004, http://dx.doi.org/10.1136/thx.2003...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01428-15
更新日期:2015-12-31 00:00:00
abstract::The generation rate constants for the steady-state growth of antibiotic-inhibited Escherichia coli have the same formal dependency on concentration for deoxylincomycin, lincomycin (phase I), erythromycin, clindamycin, and U24729A. They may be kinetically classified as a group A, in which the first three compounds comp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.5.574
更新日期:1973-11-01 00:00:00
abstract::The opportunistic Gram-negative pathogen Pseudomonas aeruginosa, known for its intrinsic and acquired antibiotic resistance, has a notorious ability to form biofilms, which often facilitate chronic infections. The evolutionary paths to antibiotic resistance have mainly been investigated in planktonic cultures and are ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00320-18
更新日期:2018-07-27 00:00:00
abstract::Here, we report the isolation of 31 Acinetobacter baumannii strains producing OXA-253 in a single large Brazilian city. These strains belonged to five different sequence types (STs), including 4 STs not previously associated with blaOXA-253 In all strains, the blaOXA-253 gene was located in a plasmid within a genetic ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01309-16
更新日期:2016-12-27 00:00:00
abstract::Statins are inhibitors of cholesterol synthesis, but other biological properties, such as antimicrobial effects, have also been assigned to them, leading to their designation as pleiotropic agents. Our goal was to investigate the activity and selectivity of atorvastatin (AVA) against Trypanosoma cruzi by using in vitr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00979-18
更新日期:2018-08-27 00:00:00
abstract::The susceptibilities of 430 Campylobacter jejuni strains and 79 C. coli strains to six antimicrobial agents were tested and analyzed. The two sets of strains originated from retail market chicken and turkey samples and from humans, respectively, in Berlin, Germany. Two groups of isolates, one dating from 1991 and the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.12.3825-3830.2003
更新日期:2003-12-01 00:00:00
abstract::A structurally diverse library of 93 lipophilic di- and tricyclic diaminopyrimidine derivatives was tested for the ability to inhibit recombinant dihydrofolate reductase (DHFR) cloned from human and bovine isolates of Cryptosporidium parvum (J. R. Vásquez et al., Mol. Biochem. Parasitol. 79:153-165, 1996). In parallel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3293-3303.2001
更新日期:2001-12-01 00:00:00
abstract::β-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β' subunit (RpoC) in slow-vancomycin-i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00712-18
更新日期:2019-01-29 00:00:00
abstract::Mycobacterium chimaera is a slow-growing nontuberculous Mycobacterium species belonging to the Mycobacterium avium complex (MAC). It has been identified globally as the cause of a large outbreak of cardiovascular infections following open heart surgery, but it can also cause respiratory infections in individuals with ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00755-19
更新日期:2019-08-23 00:00:00
abstract::Ofloxacin, a potent quinolone antibacterial agent, has a tricyclic ring structure with a methyl group attached to the asymmetric carbon at the C-3 position on the oxazine ring. The S isomer (DR-3355) of ofloxacin has antibacterial activity up to 2 orders of magnitude greater than that of the R isomer (DR-3354). This d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.8.1775
更新日期:1996-08-01 00:00:00
abstract::Biofilm production is an important step in the pathogenesis of Staphylococcus epidermidis polymer-associated infections and depends on the expression of the icaADBC operon leading to the synthesis of a polysaccharide intercellular adhesin. A chromosomally encoded reporter gene fusion between the ica promoter and the b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.12.3357-3363.2000
更新日期:2000-12-01 00:00:00
abstract::The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococca...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1507
更新日期:1987-10-01 00:00:00
abstract::Fluconazole, an inhibitor of certain human cytochrome P-450 isozymes, is used for the prevention and treatment of a broad range of fungal infections that predominantly affect immunocompromised individuals. This study evaluated the influence of fluconazole on the steady-state pharmacokinetics of delavirdine, a nonnucle...
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.41.9.1892
更新日期:1997-09-01 00:00:00
abstract::We have cloned a 4.9-kilobase (kb) HincII fragment which contains a tetracycline resistance determinant (tetM) from the chromosome of Ureaplasma urealyticum. The 4.9-kb HincII fragment contains DNA in addition to the structural gene, is closely related to the previously characterized 5.0-kb fragment from pJI3, and con...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1852
更新日期:1987-11-01 00:00:00