Jacob E. Choby
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View article: Combinatorial action of regulatory systems generates colistin heteroresistance
Combinatorial action of regulatory systems generates colistin heteroresistance Open
Heteroresistance is a form of antibiotic resistance in which a minor subpopulation of resistant cells coexists with a majority susceptible population. Colistin heteroresistance is common among Enterobacter cloacae clinical isolates, threat…
View article: Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline
Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline Open
Our understanding of the rapid adaptation of bacteria to resist novel drugs is growing beyond known mechanisms such as mobile genetic elements and mutation selection. Heteroresistance (HR) is a form of antibiotic resistance where a phenoty…
View article: Metabolic heterogeneity coupled with a resistance gene generates antibiotic heteroresistance
Metabolic heterogeneity coupled with a resistance gene generates antibiotic heteroresistance Open
Heteroresistance is a form of antibiotic resistance in which a phenotypically unstable subpopulation of resistant cells exists within a majority population of susceptible cells. The impact of the extracellular environment on mechanisms of …
View article: Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance
Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance Open
Antibiotics are considered one of the most important contributions to clinical medicine in the last century. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One form…
View article: Theoretical Considerations and Empirical Predictions of the Pharmaco- and Population Dynamics of Heteroresistance
Theoretical Considerations and Empirical Predictions of the Pharmaco- and Population Dynamics of Heteroresistance Open
Antibiotics are considered one of the most important contributions to clinical medicine in the last 100 years. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One fo…
View article: Maintenance of heme homeostasis in <i>Staphylococcus aureus</i> through post-translational regulation of glutamyl-tRNA reductase
Maintenance of heme homeostasis in <i>Staphylococcus aureus</i> through post-translational regulation of glutamyl-tRNA reductase Open
Staphylococcus aureus is an important human pathogen responsible for a variety of infections including skin and soft tissue infections, endocarditis, and sepsis. The combination of increasing antibiotic resistance in this pathogen and the …
View article: Translocation of gut commensal bacteria to the brain
Translocation of gut commensal bacteria to the brain Open
The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosi…
View article: Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline
Copy number flexibility facilitates heteroresistance to increasing antibiotic pressure and threatens the beta-lactam pipeline Open
It is unclear how bacteria rapidly adapt to resist novel drugs upon their introduction. Heteroresistance (HR) is a form of antibiotic resistance where a phenotypically unstable minority resistant subpopulation co-exists with a susceptible …
View article: LB16. Surveillance Rates of Cefiderocol Heteroresistance Correlate With All-cause Mortality in the APEKS-NP and CREDIBLE-CR Trials
LB16. Surveillance Rates of Cefiderocol Heteroresistance Correlate With All-cause Mortality in the APEKS-NP and CREDIBLE-CR Trials Open
Background Cefiderocol is a recently FDA approved, novel siderophore beta-lactam antibiotic. Conventional antimicrobial susceptibility testing (AST) suggests that a variety of Gram-negative pathogens, including carbapenem-resistant (CR) is…
View article: Antibiotic-Selected Gene Amplification Heightens Metal Resistance
Antibiotic-Selected Gene Amplification Heightens Metal Resistance Open
To inhibit bacterial transmission and infection, health care facilities use bactericidal metal coatings to prevent colonization of surfaces and implanted devices. In these environments, antibiotics are commonly used, but their effect on me…
View article: Hypervirulent <i>Klebsiella pneumoniae</i> – clinical and molecular perspectives
Hypervirulent <i>Klebsiella pneumoniae</i> – clinical and molecular perspectives Open
Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. pneumoniae (cKp) and capable of causing community‐acquired infections, often in healthy individuals. hvKp is ca…
View article: Staphylococcus aureus Coproporphyrinogen III Oxidase Is Required for Aerobic and Anaerobic Heme Synthesis
Staphylococcus aureus Coproporphyrinogen III Oxidase Is Required for Aerobic and Anaerobic Heme Synthesis Open
Heme is a critical molecule required for aerobic and anaerobic respiration by organisms across kingdoms. The human pathogen Staphylococcus aureus has served as a model organism for the study of heme synthesis and heme-dependent physiology …
View article: Control of Metabolite Flux during the Final Steps of Heme <i>b</i> Biosynthesis in Gram-Positive Bacteria
Control of Metabolite Flux during the Final Steps of Heme <i>b</i> Biosynthesis in Gram-Positive Bacteria Open
The pathway for assembling heme ends with a unique set of enzymes in Gram-positive bacteria. Substrates for these reactions include coproporphyrin III, Fe(II), and H2O2, which are highly reactive and toxic. Because these bacteria lack memb…
View article: Manganese Detoxification by MntE Is Critical for Resistance to Oxidative Stress and Virulence of <i>Staphylococcus aureus</i>
Manganese Detoxification by MntE Is Critical for Resistance to Oxidative Stress and Virulence of <i>Staphylococcus aureus</i> Open
Manganese (Mn) is generally viewed as a critical nutrient that is beneficial to pathogenic bacteria due to its function as an enzymatic cofactor and its capability of acting as an antioxidant; yet paradoxically, high concentrations of this…
View article: A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during<i>Acinetobacter baumannii</i>Infection
A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during<i>Acinetobacter baumannii</i>Infection Open
Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a …
View article: Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus
Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus Open
During infection, bacteria must steal metals, including iron, from the host tissue. Therefore, pathogenic bacteria have evolved metal acquisition systems to overcome the elaborate processes mammals use to withhold metal from pathogens. Sta…
View article: Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic<i>Staphylococcus</i>
Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic<i>Staphylococcus</i> Open
Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease. However…
View article: <i>Staphylococcus aureus</i> HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis
<i>Staphylococcus aureus</i> HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis Open
Staphylococcus aureus is responsible for a significant amount of devastating disease. Its ability to colonize the host and cause infection is supported by a variety of proteins that are dependent on the cofactor heme. Heme is a porphyrin u…