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Paul D. Phillips
Northern Arizona University, United States

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Preprint content
Published: 04 December 2019
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Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genotype/phenotype association studies. However, performing genotype/phenotype association studies is complicated by the plastic nature of the A. baumannii pan-genome. In this study, we compared the antibiograms of 12 antimicrobials associated with multiple drug families for 84 A. baumannii isolates, many isolated in Arizona, USA. in silico screening of these genomes for known AMR mechanisms failed to identify clear correlations for most drugs. We then performed a genome wide association study (GWAS) looking for associations between all possible 21-mers; this approach generally failed to identify mechanisms that explained the resistance phenotype. In order to decrease the genomic noise associated with population stratification, we compared four phylogenetically-related pairs of isolates with differing susceptibility profiles. RNA-Sequencing (RNA-Seq) was performed on paired isolates and differentially expressed genes were identified. In these isolate pairs, we identified four different potential mechanisms, highlighting the difficulty of broad AMR surveillance in this species. To verify and validate differential expression, amplicon sequencing was performed. These results suggest that a diagnostic platform based on gene expression rather than genomics alone may be beneficial in certain surveillance efforts. The implementation of such advanced diagnostics coupled with increased AMR surveillance will potentially improve A. baumannii infection treatment and patient outcomes.

ACS Style

Chandler Roe; Charles H.D. Williamson; Adam J. Vazquez; Kristen Kyger; Michael Valentine; Jolene R. Bowers; Paul D. Phillips; Veronica Harrison; Elizabeth Driebe; David M. Engelthaler; Jason W. Sahl. Bacterial Genome wide association studies (bGWAS) and transcriptomics identifies cryptic antimicrobial resistance mechanisms in Acinetobacter baumannii. 2019, 864462 .

AMA Style

Chandler Roe, Charles H.D. Williamson, Adam J. Vazquez, Kristen Kyger, Michael Valentine, Jolene R. Bowers, Paul D. Phillips, Veronica Harrison, Elizabeth Driebe, David M. Engelthaler, Jason W. Sahl. Bacterial Genome wide association studies (bGWAS) and transcriptomics identifies cryptic antimicrobial resistance mechanisms in Acinetobacter baumannii. . 2019; ():864462.

Chicago/Turabian Style

Chandler Roe; Charles H.D. Williamson; Adam J. Vazquez; Kristen Kyger; Michael Valentine; Jolene R. Bowers; Paul D. Phillips; Veronica Harrison; Elizabeth Driebe; David M. Engelthaler; Jason W. Sahl. 2019. "Bacterial Genome wide association studies (bGWAS) and transcriptomics identifies cryptic antimicrobial resistance mechanisms in Acinetobacter baumannii." , no. : 864462.

Review
Published: 13 February 2019 in Toxins
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Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of marine snails of genus Conus. α-CTxs are potent and selective antagonists for a variety of nAChR isoforms. Over the past 40 years, α-CTxs have proven to be valuable molecular probes capable of differentiating between closely related nAChR subtypes and have contributed greatly to understanding the physiological role of nAChRs in the mammalian nervous system. Here, we review the amino acid composition and structure of several α-CTxs that selectively target nAChR isoforms and explore strategies and outcomes for introducing mutations in native α-CTxs to direct selectivity and enhance binding affinity for specific nAChRs. This review will focus on structure-activity relationship studies involving native α-CTxs that have been rationally mutated and molecular interactions that underlie binding between ligand and nAChR isoform.

ACS Style

Matthew W. Turner; Leanna A. Marquart; Paul D. Phillips; Owen M. McDougal. Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors. Toxins 2019, 11, 113 .

AMA Style

Matthew W. Turner, Leanna A. Marquart, Paul D. Phillips, Owen M. McDougal. Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors. Toxins. 2019; 11 (2):113.

Chicago/Turabian Style

Matthew W. Turner; Leanna A. Marquart; Paul D. Phillips; Owen M. McDougal. 2019. "Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors." Toxins 11, no. 2: 113.