Christine Tkaczyk
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View article: The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice
The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice Open
Clostridioides difficile is the leading cause of antibiotic-associated intestinal infections. The pathogenesis of C. difficile infection (CDI) is driven by two protein exotoxins, TcdA and TcdB. The TcdB-targeting monoclonal antibody (mAb) …
View article: Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary <i>Clostridioides difficile</i> Isolates
Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary <i>Clostridioides difficile</i> Isolates Open
Background Clostridioides difficile toxin B is a virulence factor for C. difficile infections and a clinically validated target for prevention of C. difficile infection recurrence. AZD5148 is a toxin B–neutralizing human monoclonal antibod…
View article: Structure of ClfA002 in Complex With Neutralizing Antibody AZD7745 Provides Insight into Its Broad Neutralization Mechanism in <i>Staphylococcus aureus</i> Infection
Structure of ClfA002 in Complex With Neutralizing Antibody AZD7745 Provides Insight into Its Broad Neutralization Mechanism in <i>Staphylococcus aureus</i> Infection Open
Background Complications due to Staphylococcus aureus infections are a major health concern as current therapies lack broad coverage; therefore, development of a broad neutralizing therapy is critical. We previously showed that a monoclona…
View article: P-1055. Anti-Toxin B Neutralizing Monoclonal Antibody AZD5148 Provides Protection in a <i>Clostridioides difficile</i> Gnotobiotic Piglet Model
P-1055. Anti-Toxin B Neutralizing Monoclonal Antibody AZD5148 Provides Protection in a <i>Clostridioides difficile</i> Gnotobiotic Piglet Model Open
Background Clostridioides difficile infection (CDI) cause mild to severe diarrhea and can be life threatening. Because toxin B is a clinically validated target for CDI, we have generated an anti-toxin B neutralizing monoclonal antibody (mA…
View article: Association of <i>Staphylococcus aureus</i> Bacterial Load and Colonization Sites With the Risk of Postoperative <i>S. aureus</i> Infection
Association of <i>Staphylococcus aureus</i> Bacterial Load and Colonization Sites With the Risk of Postoperative <i>S. aureus</i> Infection Open
Background The independent effects of extranasal-only carriage, carriage at multiple bodily sites, or the bacterial load of colonizing Staphylococcus aureus (SA) on the risk of developing SA surgical site infections and postoperative blood…
View article: A fungal metabolic regulator underlies infectious synergism during<i>Candida albicans</i>-<i>Staphylococcus</i>aureus intra-abdominal co-infection
A fungal metabolic regulator underlies infectious synergism during<i>Candida albicans</i>-<i>Staphylococcus</i>aureus intra-abdominal co-infection Open
Candida albicans and Staphylococcus aureus are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection…
View article: 683. Understanding <i>Clostridioides difficile</i> toxinB gene conservation through surveillance of public data
683. Understanding <i>Clostridioides difficile</i> toxinB gene conservation through surveillance of public data Open
Background Clostridioides difficile infection (CDI) is the leading cause of antibiotic and healthcare-associated infective diarrhea. It is linked to 365,000 infections and causes approximately 20,000 deaths annually in the US. CDI is media…
View article: Postoperative <i>Staphylococcus aureus</i> Infections in Patients With and Without Preoperative Colonization
Postoperative <i>Staphylococcus aureus</i> Infections in Patients With and Without Preoperative Colonization Open
Importance Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiolo…
View article: Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against Staphylococcus aureus-induced acute circulatory failure in a mechanically ventilated rabbit model of hyperdynamic septic shock
Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against Staphylococcus aureus-induced acute circulatory failure in a mechanically ventilated rabbit model of hyperdynamic septic shock Open
Background Patients with septic shock caused by Staphylococcus aureus have mortality rates exceeding 50%, despite appropriate antibiotic therapy. Our objectives were to establish a rabbit model of S. aureus septic shock and to determine wh…
View article: Developing an Image Based Deep Learning Approach to Immune Cell Quantification in a Mouse Asthma Model
Developing an Image Based Deep Learning Approach to Immune Cell Quantification in a Mouse Asthma Model Open
Journal Article Developing an Image Based Deep Learning Approach to Immune Cell Quantification in a Mouse Asthma Model Get access Jonathan Boyd, Jonathan Boyd Dynamic Omics, Centre of Genomics Research, Discovery Sciences, BioPharmaceutica…
View article: Neutralizing Staphylococcus aureus Virulence with AZD6389, a Three mAb Combination, Accelerates Closure of a Diabetic Polymicrobial Wound
Neutralizing Staphylococcus aureus Virulence with AZD6389, a Three mAb Combination, Accelerates Closure of a Diabetic Polymicrobial Wound Open
Diabetic foot ulcers (DFU) represent a major complication of diabetes and are associated with poor quality of life and increased morbidity and mortality despite standard of care. They have a complex pathogenesis starting with superficial s…
View article: Multimechanistic Monoclonal Antibody Combination Targeting Key Staphylococcus aureus Virulence Determinants in a Rabbit Model of Prosthetic Joint Infection
Multimechanistic Monoclonal Antibody Combination Targeting Key Staphylococcus aureus Virulence Determinants in a Rabbit Model of Prosthetic Joint Infection Open
In a rabbit model of methicillin-resistant Staphylococcus aureus prosthetic joint infection (PJI), prophylaxis with AZD6389*—a combination of three monoclonal antibodies targeting alpha-hemolysin, bicomponent cytotoxins (LukSF/LukED/HlgAB/…
View article: 1486. Phylogenetic and alpha toxin variant analyses of <i>Staphylococcus aureus</i> strains isolated from patients during the SAATELLITE study
1486. Phylogenetic and alpha toxin variant analyses of <i>Staphylococcus aureus</i> strains isolated from patients during the SAATELLITE study Open
Background Suvratoxumab is a human monoclonal antibody that neutralizes S. aureus (SA) alpha toxin (AT). SAATELLITE, a phase 2 study of the safety and efficacy of suvratoxumab for reducing the incidence of SA pneumonia (NCT02296320), was c…
View article: Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia
Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia Open
Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins.
View article: 713. Preventive Administration of MEDI6389, a Combination of Monoclonal Antibodies (mAbs) Targeting Alpha-Toxin (AT), Panton-Valentine Leukocidin (PVL), Leukocidin ED (LukED), Gamma-Hemolysin and Clumping Factor A (ClfA), in a Rabbit Model of USA300 MRSA Prosthetic Joint Infection (PJI)
713. Preventive Administration of MEDI6389, a Combination of Monoclonal Antibodies (mAbs) Targeting Alpha-Toxin (AT), Panton-Valentine Leukocidin (PVL), Leukocidin ED (LukED), Gamma-Hemolysin and Clumping Factor A (ClfA), in a Rabbit Model of USA300 MRSA Prosthetic Joint Infection (PJI) Open
Background mAbs targeting staphylococcal virulence factors could represent an interesting preventive strategy in PJI. We evaluate here MEDI6389 compared with isotype-matched control IgG (c-IgG) in a rabbit model of USA300 MRSA PJI. Methods…
View article: Candida albicans Augments Staphylococcus aureus Virulence by Engaging the Staphylococcal<i>agr</i>Quorum Sensing System
Candida albicans Augments Staphylococcus aureus Virulence by Engaging the Staphylococcal<i>agr</i>Quorum Sensing System Open
Relatively little is known about the complex interactions and signaling events that occur between microbes and even less so about how microbial “cross talk” shapes human health and disease. Candida albicans (a fungus) and Staphylococcus au…
View article: Efficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in Mice
Efficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in Mice Open
Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus . We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, Lu…
View article: Associations of pathogen‐specific and host‐specific characteristics with disease outcome in patients with <i>Staphylococcus aureus</i> bacteremic pneumonia
Associations of pathogen‐specific and host‐specific characteristics with disease outcome in patients with <i>Staphylococcus aureus</i> bacteremic pneumonia Open
Objective To understand the relationships of Staphylococcus aureus (SA) bacteremic pneumonia (SABP) outcome with patient‐specific and SA‐specific variables. Methods We analysed SA bloodstream isolates and matching sera in SABP patients by …
View article: Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets
Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets Open
Bacterial biofilm infections of implantable medical devices decrease the effectiveness of antibiotics, creating difficult-to-treat chronic infections. Prosthetic joint infections (PJI) are particularly problematic because they require prol…
View article: Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity <i>In Vitro</i> and Staphylococcus aureus Fitness in Infection Models
Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity <i>In Vitro</i> and Staphylococcus aureus Fitness in Infection Models Open
Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis; consequently, extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel …
View article: Alanine scanning mutagenesis of the MEDI4839 (Suvratoxumab) epitope reduces alpha toxin lytic activity <i>in vitro</i> and <i>S. aureus</i> fitness in infection models
Alanine scanning mutagenesis of the MEDI4839 (Suvratoxumab) epitope reduces alpha toxin lytic activity <i>in vitro</i> and <i>S. aureus</i> fitness in infection models Open
Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis, consequently extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel p…
View article: Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone
Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone Open
Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human mon…
View article: Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound Isolates
Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound Isolates Open
Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofi…
View article: S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking
S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking Open
Clinical severity of Staphylococcus aureus respiratory infection correlates with alpha toxin (AT) expression. AT activates the NLRP3 inflammasome; deletion of Nlrp3, or AT neutralization, protects mice from lethal S. aureus pneumonia. We t…