Abstract:
:Invasive aspergillosis (IA) is a severe condition mainly caused by Aspergillus fumigatus, although other species of the genus, such as section Nigri members, can also be involved. Voriconazole (VRC) is the recommended treatment for IA; however, the prevalence of azole-resistant Aspergillus isolates has alarmingly increased in recent years, and the underlying resistance mechanisms in non-fumigatus species remain unclear. We have determined the in vitro susceptibility of 36 strains from section Nigri to VRC, posaconazole (POS), and itraconazole (ITC), and we have explored the role of Cyp51A and Cyp51B, both targets of azoles, in azole resistance. The three drugs were highly active; POS displayed the best in vitro activity, while ITC and VRC showed MICs above the established epidemiological cutoff values in 9 and 16% of the strains, respectively. Furthermore, expression studies of cyp51A and cyp51B in control condition and after VRC exposure were performed in 14 strains with different VRC susceptibility. We found higher transcription of cyp51A, which was upregulated upon VRC exposure, but no correlation between MICs and cyp51 transcription levels was observed. In addition, cyp51A sequence analyses revealed nonsynonymous mutations present in both, wild-type and non-wild-type strains of A. niger and A. tubingensis Nevertheless, a few mutations were exclusively present in non-wild-type A. tubingensis strains. Altogether, our results suggest that azole resistance in section Nigri is not clearly explained by Cyp51A protein alteration or by cyp51 gene upregulation, which indicates that other mechanisms might be involved.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Pérez-Cantero A,López-Fernández L,Guarro J,Capilla Jdoi
10.1128/AAC.00543-19subject
Has Abstractpub_date
2019-06-24 00:00:00issue
7eissn
0066-4804issn
1098-6596pii
AAC.00543-19journal_volume
63pub_type
杂志文章abstract::The most deadly outbreak of Escherichia coli O104:H4 occurred in Europe in 2011. Here, we evaluated the effects of the retrograde trafficking inhibitor Retro-2(cycl) in a murine model of E. coli O104:H4 infection. Systemic treatment with Retro-2(cycl) significantly reduced body weight loss and improved clinical scores...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00455-15
更新日期:2015-08-01 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::It has recently become apparent that inflammatory reactions including nitric oxide (NO) release contribute to the outcome of pulmonary infections. To investigate the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on the pathogenesis of pneumococcal pneumonia, we inoculated CD(1) Swiss mice wit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.9.2283
更新日期:1999-09-01 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::The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00425-10
更新日期:2010-10-01 00:00:00
abstract::Polymyxin B (PMB) binds to and neutralizes endotoxin, but its systemic clinical utility is limited by neuro- and nephrotoxicity. PMX622 is a covalent conjugate of PMB and Dextran-70 designed to retain the ability of PMB to neutralize endotoxin and to retain the favorable colloidal, pharmacokinetic, and metabolic prope...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.2987-2992.2004
更新日期:2004-08-01 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::The methionyl-tRNA synthetase (MetRS) is a novel drug target for the protozoan pathogen Giardia intestinalis. This protist contains a single MetRS that is distinct from the human cytoplasmic MetRS. A panel of MetRS inhibitors was tested against recombinant Giardia MetRS, Giardia trophozoites, and mammalian cell lines....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01573-15
更新日期:2015-11-01 00:00:00
abstract::We used the Tn10-encoded Tet repressor, which has a highly specific binding capacity for tetracycline, to probe contacts between the drug and protein by chemical interference studies of the antibiotic. For that purpose, the equilibrium association constants of modified tetracyclines with the Tet repressor and Mg2+ cat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.8.1591
更新日期:1991-08-01 00:00:00
abstract::At least four broad-spectrum efflux pumps (Mex) are involved in elevated intrinsic antibiotic resistance as well as in acquired multidrug resistance in Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY) of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.7.2169-2173.2002
更新日期:2002-07-01 00:00:00
abstract::Hemicholinium 3, decamethonium, and decyltrimethylammonium previously have been demonstrated to be efficient inhibitors, with 50% inhibitory concentrations of 4 X 10(-6), 10(-6), and 7 X 10(-7) M, respectively. We show that lengthening of the alkyl chain of decyltrimethylammonium by successive additions of two carbon ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.5.814
更新日期:1986-05-01 00:00:00
abstract::We have determined the antifungal susceptibilities of 34 clinical isolates of the dimorphic fungus Sporothrix schenckii to 11 drugs using a microdilution method. In general, the type of growth phase (mycelial or yeast) and the temperature of incubation (30 or 35 degrees C) exerted a significant influence on the MICs. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3952-3954.2005
更新日期:2005-09-01 00:00:00
abstract::The exogenous control of hepatitis C virus (HCV) replication can be mediated through the inhibition of the RNA-dependent RNA polymerase (RdRp) activity of NS5B. Small-molecule inhibitors of NS5B include nucleoside and nonnucleoside analogs. Here, we report the discovery of a novel class of HCV polymerase nonnucleoside...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00669-08
更新日期:2008-12-01 00:00:00
abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05760-11
更新日期:2012-03-01 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::We have recently cloned a DNA fragment containing a gene cluster that is responsible for the biosynthesis of an antituberculosis antibiotic, D-cycloserine. The gene cluster is composed of 10 open reading frames, designated dcsA to dcsJ. Judging from the sequence similarity between each putative gene product and known ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02291-12
更新日期:2013-06-01 00:00:00
abstract::Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-d-2'-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00318-16
更新日期:2016-07-22 00:00:00
abstract::Omadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/pharmacodynamic (PK/P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02058-19
更新日期:2020-01-27 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::A total of 20 serious infections were treated with piperacillin. These infections included bacteremias (5), pneumonias (5), urinary tract infections (5), soft tissue infections (3), septic arthritis (1), and osteomyelitis (1). The most common bacterial pathogen was Pseudomonas aeruginosa, accounting for eight infectio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.18.1.167
更新日期:1980-07-01 00:00:00
abstract::Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.8.1683
更新日期:1995-08-01 00:00:00
abstract::Ethambutol at 3.0 micrograms/ml inhibited the transfer of label from D-[14C]glucose into the D-arabinose residue of arabinogalactan in whole cells of a drug-susceptible strain of Mycobacterium smegmatis. This inhibition began almost immediately after exposure of the cells to the drug. When drug-resistant M. smegmatis ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1493
更新日期:1989-09-01 00:00:00
abstract::Acanthamoeba is a free-living amoeba causing a potentially blinding infection of the cornea. Contact lens wearers are most at risk and account for some 95% of cases. Hydrogen peroxide is used for contact lens disinfection due to its broad antimicrobial activity. Lenses must be neutralized before use to avoid pronounce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.7.2038-2043.2001
更新日期:2001-07-01 00:00:00
abstract::Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00801-10
更新日期:2010-12-01 00:00:00
abstract::The pharmacokinetics of gentamicin in 34 febrile neutropenic patients (40 courses) were compared with those in 40 nonneutropenic patients receiving the drug. No pharmacokinetic differences were seen in half-life, volume of distribution (liter per kilogram; total and ideal body weight), or clearance (milliliter per min...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.11.1890
更新日期:1989-11-01 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::The in vitro activities of luliconazole, amorolfine, ciclopirox, and terbinafine were determined against 320 dermatophyte isolates from large toenails of onychomycosis patients enrolled into an ongoing phase 2b/3 clinical study. The geometric mean MIC for luliconazole was 0.00022 μg/ml against all isolates, compared t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02706-13
更新日期:2014-06-01 00:00:00
abstract::BO-1341, a new antipseudomonal semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefotaxime, and cefoperazone. The in vitro activity of BO-1341 was generally superior or comparable to the activities of the reference antibiotics against clinical...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1423
更新日期:1989-09-01 00:00:00
abstract::The penamaldic derivatives of amoxicillin, ampicillin, and penicillins G and V, stabilized with Zn(2+), were obtained from a methanolic medium. The enzymatic kinetic results show that the these derivatives elicit reversible inhibition of the enzyme metallo-beta-lactamase from Bacillus cereus, with inhibition constant ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.3.1058-1060.2004
更新日期:2004-03-01 00:00:00
abstract::Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polyproteins in cultures of human immunodeficiency virus type 1 (HIV-1)-infected T lymphocytes and, as a result, inhibit the infectivity of HIV-1 for such cultures. The ability of HIV-1 protease inhibitors to suppress repl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.1.71
更新日期:1993-01-01 00:00:00