Stephanie M. Reeve
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View article: Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria
Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria Open
Dihydropteroate synthase (DHPS) is a critical enzyme in the folate biosynthetic pathway of bacteria, fungi, and protozoans. Sulfonamides successfully target the p-aminobenzoic acid (pABA) binding site of DHPS, forming a false…
View article: Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in<i>Mycobacterium</i>abscessus
Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in<i>Mycobacterium</i>abscessus Open
Mycobacterium abscessus ( Mab ), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop…
View article: A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance
A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance Open
Detailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics and diagnostics. It is thereby key to develop a comprehensive genome-wide understanding of how bacteria proces…
View article: Synthesis and Structure–Activity Relationship of Thioacetamide-Triazoles against Escherichia coli
Synthesis and Structure–Activity Relationship of Thioacetamide-Triazoles against Escherichia coli Open
Infections due to Gram-negative bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. We have previously identified a novel …
View article: Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus
Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus Open
Antimicrobial resistance presents a significant health care crisis. The mutation F98Y in Staphylococcus aureus dihydrofolate reductase (SaDHFR) confers resistance to the clinically important antifolate trimethoprim (TMP). Propargyl-linked …
View article: A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance
A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance Open
Detailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics and diagnostics. It is thereby key to develop a comprehensive genome-wide understanding of how bacteria proces…
View article: Combating Multidrug‐Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling
Combating Multidrug‐Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling Open
Multidrug‐resistant bacteria are causing a serious global health crisis. A dramatic decline in antibiotic discovery and development investment by pharmaceutical industry over the last decades has slowed the adoption of new technologies. It…
View article: Synthesis, antibacterial action, and ribosome inhibition of deoxyspectinomycins
Synthesis, antibacterial action, and ribosome inhibition of deoxyspectinomycins Open
View article: 1233. Identification of Novel Inhibitors of <i>Clostridioides difficile</i> Enoyl-Reductase II (FabK) by High-Throughput Virtual and Experimental Screening
1233. Identification of Novel Inhibitors of <i>Clostridioides difficile</i> Enoyl-Reductase II (FabK) by High-Throughput Virtual and Experimental Screening Open
Background Clostridioides difficile is one of only three bacteria categorized as an ‘urgent’ drug-resistant threat by the CDC. This pathogen is responsible for nearly 500,000 hospital-acquired infections and 29,000 deaths per year at a cos…
View article: Chiral evasion and stereospecific antifolate resistance in<i>Staphylococcus aureus</i>
Chiral evasion and stereospecific antifolate resistance in<i>Staphylococcus aureus</i> Open
Antimicrobial resistance is a health care crisis. The resistance-conferring mutation F98Y in Staphylococcus aureus dihydrofolate reductase (SaDHFR) reduces effectiveness of antifolates, e.g., trimethoprim (TMP). Although propargyl-linked a…
View article: A Rare Bacteria: Lactobacillus Rhamnosus in Pediatric Lung Abscess
A Rare Bacteria: Lactobacillus Rhamnosus in Pediatric Lung Abscess Open
View article: Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant<i>Klebsiella pneumoniae</i>and<i>Enterobacter cloacae</i>
Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant<i>Klebsiella pneumoniae</i>and<i>Enterobacter cloacae</i> Open
Antimicrobial resistance is causing a global human health crisis and is affecting all antibiotic classes. While β-lactams have been commonly used against susceptible isolates of Klebsiella pneumoniae and Enterobacter cloacae , carbapenem-r…
View article: Discovery and Characterization of the Antimetabolite Action of Thioacetamide-Linked 1,2,3-Triazoles as Disruptors of Cysteine Biosynthesis in Gram-Negative Bacteria
Discovery and Characterization of the Antimetabolite Action of Thioacetamide-Linked 1,2,3-Triazoles as Disruptors of Cysteine Biosynthesis in Gram-Negative Bacteria Open
Increasing rates of drug-resistant Gram-negative (GN) infections, combined with a lack of new GN-effective antibiotic classes, are driving the need for the discovery of new agents. Bacterial metabolism represents an underutilized mechanism…
View article: Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates
Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates Open
View article: Toward Broad Spectrum DHFR inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin-Resistant <i>Staphylococcus aureus</i>
Toward Broad Spectrum DHFR inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin-Resistant <i>Staphylococcus aureus</i> Open
The spread of plasmid borne resistance enzymes in clinical Staphylococcus aureus isolates is rendering trimethoprim and iclaprim, both inhibitors of dihydrofolate reductase (DHFR), ineffective. Continued exploitation of these targets will …
View article: OSPREY Predicts Resistance Mutations Using Positive and Negative Computational Protein Design
OSPREY Predicts Resistance Mutations Using Positive and Negative Computational Protein Design Open
View article: MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates
MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates Open
View article: Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis
Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis Open
Mycobacterium tuberculosis continues to cause widespread, life-threatening disease. In the last decade, this threat has grown dramatically as multi- and extensively-drug resistant (MDR and XDR) bacteria have spread globally and the number …
View article: Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations
Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations Open
Drug-resistant enzymes must balance catalytic function with inhibitor destabilization to provide a fitness advantage. This sensitive balance, often involving very subtle structural changes, must be achieved through a selection process invo…
View article: Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens Open
Although classical, negatively charged antifolates such as methotrexate possess high affinity for the dihydrofolate reductase (DHFR) enzyme, they are unable to penetrate the bacterial cell wall, rendering them poor antibacterial agents. He…
View article: Understanding the Structural Mechanisms of Antibiotic Resistance Sets the Platform for New Discovery
Understanding the Structural Mechanisms of Antibiotic Resistance Sets the Platform for New Discovery Open
Understanding the structural basis of antibacterial resistance may enable rational design principles that avoid and subvert that resistance, thus leading to the discovery of more effective antibiotics. In this review, we explore the use of…
View article: Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in <i>S</i>. <i>aureus</i>
Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in <i>S</i>. <i>aureus</i> Open
While antifolates such as Bactrim (trimethoprim-sulfamethoxazole; TMP-SMX) continue to play an important role in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), resistance-conferring mutations, specifical…