Abstract:
:The pathogenic yeast Candida albicans can exist in multiple morphological states, including budded, pseudohyphal, and true hyphal forms. The ability to convert between the budded and hyphal forms, termed the budded-to-hyphal-form transition, is important for virulence and is regulated by multiple environmental and cellular signals. To identify inhibitors of this morphological transition, a microplate-based morphological assay was developed. With this assay, the known actin-inhibiting drugs latrunculin-A and jasplakinolide were shown to inhibit the transition in a dose-dependent and reversible manner. Five novel small molecules that reversibly inhibited the transition and hyphal elongation without affecting budded growth were identified. These molecules inhibited hyphal growth induced by Spider, Lee's, M199 pH 8, and 10% serum-containing media, with two molecules having a synergistic effect. The molecules also differentially affected the hyphal form-specific gene expression of HWP1 and endocytosis without disrupting the actin cytoskeleton or septin organization. Structural derivatives of one of the molecules were more effective inhibiters than the original molecule, while other derivatives had decreased efficacies. Several of the small molecules were able to reduce C. albicans-dependent damage to endothelial cells by inhibiting the budded-to-hyphal-form transition. These studies substantiated the effectiveness of the morphological assay and identified several novel molecules that, by virtue of their ability to inhibit the budded-to-hyphal-form transition, may be exploited as starting points for effective antifungal therapeutics in the future.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Toenjes KA,Munsee SM,Ibrahim AS,Jeffrey R,Edwards JE Jr,Johnson DIdoi
10.1128/AAC.49.3.963-972.2005subject
Has Abstractpub_date
2005-03-01 00:00:00pages
963-72issue
3eissn
0066-4804issn
1098-6596pii
49/3/963journal_volume
49pub_type
杂志文章abstract::(1,3)Beta-D-glucan synthase (EC 2.4.1.34. UDP-glucose: 1,3-beta-D-glucan 3-beta-glucosyltransferase) uses UDP-glucose as substrate and catalyzes the polymerization of glucose ([1,3]-beta-linkages) to form the major carbohydrate component of the fungal cell wall. We have optimized in vitro assay conditions for (1,3)bet...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.7.2851-2856.2005
更新日期:2005-07-01 00:00:00
abstract::An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.398-405.2005
更新日期:2005-01-01 00:00:00
abstract::Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01122-07
更新日期:2008-02-01 00:00:00
abstract::The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, =0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, =0.125 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.633-639.2000
更新日期:2000-03-01 00:00:00
abstract::Mycobacterium tuberculosis strains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.02220-16
更新日期:2017-03-24 00:00:00
abstract::Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01269-15
更新日期:2015-11-02 00:00:00
abstract::The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.6.1290
更新日期:1992-06-01 00:00:00
abstract::Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro. Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3169
更新日期:1998-12-01 00:00:00
abstract::Sordarin derivatives constitute a new group of synthetic antifungal agents that selectively inhibit fungal protein synthesis. They have demonstrated in vitro activity against the most important fungal pathogens, both yeast and filamentous. This new family of compounds has also shown in vivo activity against murine Can...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.10.2787-2792.2001
更新日期:2001-10-01 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::Ceftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active against Enterobacteriaceae (4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including merope...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02436-12
更新日期:2013-04-01 00:00:00
abstract::The NS3/4A protease from hepatitis C virus (HCV) plays a key role in viral replication. We report a system for monitoring the activity of this enzyme in single living mammalian cells. We constructed a fluorescence resonance energy transfer (FRET) probe that consists of an enhanced cyan fluorescent protein-citrine fusi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01029-08
更新日期:2009-02-01 00:00:00
abstract::Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1235
更新日期:1991-06-01 00:00:00
abstract::Four out of 143 phenotypically isoniazid-resistant but rifampin-susceptible Mycobacterium tuberculosis strains that were isolated from patients in Germany in 2011 had mutations in the rifampin resistance-determining region of rpoB. After performing drug susceptibility testing (DST) with two methods, the proportion met...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01752-13
更新日期:2014-01-01 00:00:00
abstract::Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.356
更新日期:1981-09-01 00:00:00
abstract::The caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3616-3623.2005
更新日期:2005-09-01 00:00:00
abstract::An NDM-1 carbapenemase-producing Pseudomonas aeruginosa isolate was recovered from a patient hospitalized in France after a previous hospitalization in Serbia. Genetic studies revealed that the blaNDM-1 gene was surrounded by insertion sequence ISAba125 and a truncated bleomycin resistance gene. This blaNDM-1 region w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02334-12
更新日期:2013-07-01 00:00:00
abstract::The association of an IS440-sul3 platform with Tn21 class 1 integrons carried by IncI1 plasmids encoding extended-spectrum β-lactamases (ESBLs; mainly SHV-12 and CTX-M-14) among worldwide Escherichia coli clones of phylogroups A (ST10, ST23, and ST46), B1 (ST155, ST351, and ST359), and D/B2 (ST131) is reported. An in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01448-10
更新日期:2011-05-01 00:00:00
abstract::Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections. To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C. neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1507
更新日期:1994-07-01 00:00:00
abstract::We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression syst...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.574-577.2000
更新日期:2000-03-01 00:00:00
abstract::Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have emerged as major nosocomial pathogens. bla(KPC), commonly located on Tn4401, is found in Gram-negative bacterial strains, with the two most common variants, bla(KPC-2) and bla(KPC-3), identified in plasmids with diverse genetic backgrounds. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01648-12
更新日期:2013-01-01 00:00:00
abstract::The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.4.432
更新日期:1974-10-01 00:00:00
abstract::The site of localization of [(3)H]gentamicin within mouse kidney is shown to be the proximal renal tubule by coincidence of the radioactivity, as visualized by autoradiography, and the mucopolysaccharide-rich microvilli characteristic of proximal convoluted tubules, as visualized by histochemical staining. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.131
更新日期:1979-01-01 00:00:00
abstract::Current therapy for toxoplasmosis with a synergistic combination of pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin is not always efficacious and is frequently discontinued due to intolerable toxic effects in immunocompromised individuals, particularly those with AIDS. Trovafloxacin, a new fluoroquin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.893
更新日期:1997-05-01 00:00:00
abstract::An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, Z...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02024-17
更新日期:2018-04-26 00:00:00
abstract::Biapenem is a parenteral carbapenem antibiotic that exhibits wide-ranging antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Tebipenem is the active form of tebipenem pivoxil, a novel oral carbapenem antibiotic that has a high level of bioavailability...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01456-07
更新日期:2008-06-01 00:00:00
abstract::Acyclovir, known as an antiherpetic agent, showed an inhibitory effect on the propagation of pseudorabies virus in BHK-21 cells. The antiviral effect of acyclovir was observed by plaque reduction, as well as by the inhibition of the virus-stimulated uptake of thymidine by BHK-21 cells. Amphotericin B potentiated the a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.119
更新日期:1983-01-01 00:00:00
abstract::Current treatments of disseminated infection caused by the Mycobacterium avium-M. intracellulare complex (MAC) are generally ineffective. Liposome-mediated delivery of antibiotics to MAC-infected tissues in vivo can enhance the efficacy of the drugs (N. Düzgüneş, V. K. Perumal, L. Kesavalu, J. A. Goldstein, R. J. Debs...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2808
更新日期:1992-12-01 00:00:00
abstract::Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01221-20
更新日期:2020-10-20 00:00:00
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 su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01652-05
更新日期:2006-07-01 00:00:00