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1.
J Clin Microbiol ; 55(7): 2030-2034, 2017 07.
Article in English | MEDLINE | ID: mdl-28404678

ABSTRACT

Aspergillus spp. cause serious invasive lung infections, and Aspergillus fumigatus is the most commonly encountered clinically significant species. Voriconazole is considered to be the drug of choice for treating A. fumigatus infections; however, rising resistance rates have been reported. We evaluated a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method for the differentiation between wild-type and non-wild-type isolates of 20 Aspergillus spp. (including 2 isolates of Aspergillus ustus and 1 of Aspergillus calidoustus that were used as controls due their intrinsic low azole susceptibility with respect to the in vitro response to voriconazole). At 30 and 48 h of incubation, there was complete agreement between Cyp51A sequence analysis, broth microdilution, and MALDI-TOF MS classification of isolates as wild type or non-wild type. In this proof-of-concept study, we demonstrated that MALDI-TOF MS can be used to accurately detect A. fumigatus strains with reduced voriconazole susceptibility. However, rather than proving to be a rapid and simple method for antifungal susceptibility testing, this particular MS-based method showed no benefit over conventional testing methods.


Subject(s)
Antifungal Agents/pharmacology , Aspergillus/drug effects , Microbial Sensitivity Tests/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Voriconazole/pharmacology , Humans , Proof of Concept Study
2.
BMC Microbiol ; 16(1): 164, 2016 07 26.
Article in English | MEDLINE | ID: mdl-27459848

ABSTRACT

BACKGROUND: The increasing emergence of drug-resistant tuberculosis presents a threat to the effective control of tuberculosis (TB). Rapid detection of drug-resistance is more important than ever to address this scourge. The purpose of this study was to genotypically characterize the first-line antitubercular drug-resistant isolates collected over 11 years in Quebec. RESULTS: The main mutations found in our resistant strains collection (n = 225) include: the S315T substitution in katG (50.2 %), the -15 C/T mutation in the inhA promoter (29 %); the S531L substitution in rpoB (43 %); the deletion 8 bp 446 / + R140S in pncA (72.9 %); the M306I (35.7 %) and M306V (21.4 %) substitutions in embB. Ten of the mutations in katG and 4 mutations identified in pncA were previously undescribed. CONCLUSION: Screening of mutations conferring resistance to first-line antituberculous drugs using DNA-sequencing approach seems to be feasible and would drastically shorten the time to determine the resistance profile compared to the proportion method.


Subject(s)
Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/microbiology , Amidohydrolases/genetics , Antitubercular Agents/pharmacology , Bacterial Proteins/genetics , Catalase/genetics , DNA, Bacterial/genetics , DNA-Directed RNA Polymerases/genetics , Genome, Bacterial , Genotype , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Oxidoreductases/genetics , Pentosyltransferases/genetics , Quebec , Sequence Analysis, DNA , Sequence Deletion , Tuberculosis/microbiology
3.
Emerg Infect Dis ; 22(2): 306-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26812599

ABSTRACT

Since the 2013 description of Blastomyces gilchristii, research describing the virulence or clinical outcome of B. gilchristii infection has been lacking. We report molecular evidence of B. gilchristii as an etiologic agent of fatal acute respiratory distress syndrome. B. gilchristii infection was confirmed by PCR and sequence analysis.


Subject(s)
Blastomyces/genetics , Blastomycosis/microbiology , Respiratory Distress Syndrome/microbiology , Adult , Antifungal Agents/therapeutic use , Blastomyces/classification , Blastomycosis/diagnosis , Blastomycosis/drug therapy , Blastomycosis/physiopathology , DNA, Intergenic , Fatal Outcome , Female , Humans , Radiography, Thoracic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/physiopathology
4.
Neuropsychopharmacology ; 33(10): 2362-75, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18004284

ABSTRACT

There is an evolutionary advantage to learning food preferences from conspecifics, as social learning allows an individual to bypass the risks associated with trial and error individual learning. The social transmission of food preferences (STFP) paradigm examines this advantage. Females in the proestrus and diestrus phases of the estrous cycle show a prolonged preference for the demonstrated food relative to estrus and ovariectomized females. Additionally, both estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) knockout mice show impaired social recognition, which suggests that both receptors may be involved in other types of socially dependent learning, including the STFP. The present study investigated the effect of the ERalpha selective agonist PPT (1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole) and the ERbeta selective agonist WAY-200070 (7-Bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol) on the STFP. Results showed that ovariectomized (ovx) mice treated with PPT failed to learn the socially acquired preference, while WAY-200070-treated ovx mice showed a two-fold prolonged preference for the food eaten by their demonstrator. The effects of PPT on the socially acquired food preference cannot be explained by effects on the total food intake of the groups or on the type of interaction with the demonstrator mouse. The effects of WAY-200070 may be partially due to effects on Submissive Behavior. The higher WAY-200070 doses produced prolonged preferences similar to those seen previously in intact female mice during the proestrus and diestrus phases. This suggests that the estrous cycle's effects on social learning may be due to the action of ERbeta on Submissive Behavior, or to ERbeta countering that of ERalpha.


Subject(s)
Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Feeding Behavior/physiology , Food Preferences/physiology , Learning/physiology , Social Behavior , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Brain/drug effects , Brain/metabolism , Dose-Response Relationship, Drug , Estradiol Congeners/pharmacology , Estrogen Receptor alpha/agonists , Estrogen Receptor beta/agonists , Estrous Cycle/physiology , Feeding Behavior/drug effects , Female , Food Preferences/drug effects , Learning/drug effects , Mice , Ovariectomy , Oxazoles/pharmacology , Phenols/pharmacology , Pyrazoles
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