Lindsey M Watson

Translational Genomics Research Institute, Phoenix, Arizona, United States

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Publications (5)17.52 Total impact

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    ABSTRACT: A PCR assay was developed to genotypically characterize F. tularensis and F. novicida. An integrated and partially redundant set of markers was selected to provide positive identification of these species, identify subspecies of F. tularensis, and genotype 14 variable number tandem repeat (VNTR) markers. Assay performance was evaluated with 117 Francisella samples. Sample DNA was amplified and the masses of the PCR products were determined with electrospray ionization/time of flight mass spectrometry (ESI-MS). The base compositions of the PCR amplicons were derived from these high-accuracy mass measurements and contrasted with databased information associated with each of the 25 assay markers. Species and subspecies determinations for all samples were fully concordant with results from established typing methods, and VNTR markers provided additional discrimination among samples. Sequence variants were observed with a number of assay markers, but these did not interfere with sample characterization, and served to increase the genetic diversity detected by the assay. Letters in Applied Microbiology © 2012 Ibis Biosciences.
    Letters in Applied Microbiology 11/2012; · 1.63 Impact Factor
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    ABSTRACT: Rates of resistance to macrolide antibiotics in Streptococcus pneumoniae are rising around the world due to the spread of mobile genetic elements harboring mef(E) and erm(B) genes and post-vaccine clonal expansion of strains that carry them. Characterization of 592 clinical isolates collected in Arizona over a 10 year period shows 23.6% are macrolide resistant. The largest portion of the macrolide-resistant population, 52%, is dual mef(E)/erm(B)-positive. All dual-positive isolates are multidrug-resistant clonal lineages of Taiwan19F-14, mostly multilocus sequence type 320, carrying the recently described transposon Tn2010. The remainder of the macrolide resistant S. pneumoniae collection includes 31% mef(E)-positive, and 9% erm(B)-positive strains. The dual-positive, multidrug-resistant S. pneumoniae clones have likely expanded by switching to non-vaccine serotypes after the heptavalent pneumococcal conjugate vaccine release, and their success limits therapy options. This upsurge could have a considerable clinical impact in Arizona.
    BMC Microbiology 01/2012; 12:12. · 2.98 Impact Factor
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    ABSTRACT: Burkholderia pseudomallei is a gram-negative bacterium that causes the serious human disease, melioidosis. There is no vaccine against melioidosis and it can be fatal if not treated with a specific antibiotic regimen, which typically includes the third-generation cephalosporin, ceftazidime (CAZ). There have been several resistance mechanisms described for B. pseudomallei, of which the best described are amino acid changes that alter substrate specificity in the highly conserved class A β-lactamase, PenA. In the current study, we sequenced penA from isolates sequentially derived from two melioidosis patients with wild-type (1.5 µg/mL) and, subsequently, resistant (16 or ≥256 µg/mL) CAZ phenotypes. We identified two single-nucleotide polymorphisms (SNPs) that directly increased CAZ hydrolysis. One SNP caused an amino acid substitution (C69Y) near the active site of PenA, whereas a second novel SNP was found within the penA promoter region. In both instances, the CAZ resistance phenotype corresponded directly with the SNP genotype. Interestingly, these SNPs appeared after infection and under selection from CAZ chemotherapy. Through heterologous cloning and expression, and subsequent allelic exchange in the native bacterium, we confirmed the role of penA in generating both low-level and high-level CAZ resistance in these clinical isolates. Similar to previous studies, the amino acid substitution altered substrate specificity to other β-lactams, suggesting a potential fitness cost associated with this mutation, a finding that could be exploited to improve therapeutic outcomes in patients harboring CAZ resistant B. pseudomallei. Our study is the first to functionally characterize CAZ resistance in clinical isolates of B. pseudomallei and to provide proven and clinically relevant signatures for monitoring the development of antibiotic resistance in this important pathogen.
    PLoS ONE 01/2012; 7(2):e30789. · 3.53 Impact Factor
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    ABSTRACT: We characterized the prevalence, antibiotic susceptibility profiles, and genotypes of Staphylococcus aureus among US meat and poultry samples (n = 136). S. aureus contaminated 47% of samples, and multidrug resistance was common among isolates (52%). S. aureus genotypes and resistance profiles differed significantly among sample types, suggesting food animal-specific contamination.
    Clinical Infectious Diseases 05/2011; 52(10):1227-30. · 9.37 Impact Factor
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    ABSTRACT: Antibiotic use in food animal production negatively impacts human health through the selection of antibiotic resistant foodborne pathogens such as Salmonella and Campylobacter. Antibiotic resistant strains of Escherichia coli and Enterococcus spp. are also common contaminants of US retail meat and poultry, and may negatively impact human health as well. To more fully evaluate consumer risk, the entire range of antibiotic resistant bacteria that contaminate the US food supply must be assessed. However, the National Antibiotic Resistance Monitoring System (NARMS) currently only surveys retail meats for Salmonella, Campylobacter, E. coli and Enterococcus. In the current study, we surveyed retail pork chops, ground beef, ground turkey, and chicken breasts from Arizona, California, District of Columbia, and Illinois for antibiotic resistant strains of Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. All four bacterial species were identified among the food samples and resistant phenotypes were common. Further studies will have to be conducted to assess the host specificities of these organisms and specifically their ability to colonize or infect humans and to share resistance determinants with human-adapted pathogens.
    138st APHA Annual Meeting and Exposition 2010; 11/2010