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View article: P-1097. Efficacy of Rifaquizinone in a Murine Model of Prosthetic Joint Infection (PJI) with Fluoroquinolone-Sensitive and -Resistant <i>Staphylococcus aureus</i>
P-1097. Efficacy of Rifaquizinone in a Murine Model of Prosthetic Joint Infection (PJI) with Fluoroquinolone-Sensitive and -Resistant <i>Staphylococcus aureus</i> Open
Background Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or…
View article: P-1111. Efficacy of Intra-Articular Administration of Rifaquizinone in Rodent Models of Implant Infection Associated with <i>Staphylococcus aureus</i>
P-1111. Efficacy of Intra-Articular Administration of Rifaquizinone in Rodent Models of Implant Infection Associated with <i>Staphylococcus aureus</i> Open
Background Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or…
View article: Inhibition of host 5-lipoxygenase reduces overexuberant inflammatory responses and mortality associated with <i>Cryptococcus</i> meningoencephalitis
Inhibition of host 5-lipoxygenase reduces overexuberant inflammatory responses and mortality associated with <i>Cryptococcus</i> meningoencephalitis Open
Cryptococcosis, caused by fungi of the genus Cryptococcus , manifests in a broad range of clinical presentations, including severe pneumonia and disease of the central nervous system (CNS) and other tissues (bone and skin). Immune deficien…
View article: Suppression of host humoral immunity by <i>Borrelia burgdorferi</i> varies over the course of infection
Suppression of host humoral immunity by <i>Borrelia burgdorferi</i> varies over the course of infection Open
Borrelia burgdorferi , the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. The resulting immune response is characteri…
View article: Surgical Primary Tumor Resection Reduces Accumulation of CD11b+ Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis
Surgical Primary Tumor Resection Reduces Accumulation of CD11b+ Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis Open
A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumor…
View article: An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions
An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions Open
Colonization of the gut and airways by pathogenic bacteria can lead to local tissue destruction and life-threatening systemic infections, especially in immunologically compromised individuals. Here, we describe an mRNA-based platform enabl…
View article: Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses
Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses Open
Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)—nasal nano-vaccine—significantly reduced lung colonizatio…
View article: mRNA delivery of dimeric human IgA protects mucosal tissues from bacterial infection
mRNA delivery of dimeric human IgA protects mucosal tissues from bacterial infection Open
Monoclonal antibody (mAb) therapy is a promising infectious disease intervention strategy but is limited to IgG1 isotypes that have restricted access to mucosal sites. IgA is well-established as the predominant antibody isotype in mucosal …
View article: Design, Synthesis, and Characterization of TNP-2198, a Dual-Targeted Rifamycin-Nitroimidazole Conjugate with Potent Activity against Microaerophilic and Anaerobic Bacterial Pathogens
Design, Synthesis, and Characterization of TNP-2198, a Dual-Targeted Rifamycin-Nitroimidazole Conjugate with Potent Activity against Microaerophilic and Anaerobic Bacterial Pathogens Open
TNP-2198, a stable conjugate of a rifamycin pharmacophore and a nitroimidazole pharmacophore, has been designed, synthesized, and evaluated as a novel dual-targeted antibacterial agent for the treatment of microaerophilic and anaerobic bac…
View article: Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes
Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes Open
A major antimicrobial resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. The increasing emergence of β-lactamase-producing multi-drug-resistant "superbugs" has resulted in increases in costly hospital …
View article: Microbiological Characterization of VNRX-5236, a Broad-Spectrum β-Lactamase Inhibitor for Rescue of the Orally Bioavailable Cephalosporin Ceftibuten as a Carbapenem-Sparing Agent against Strains of <i>Enterobacterales</i> Expressing Extended-Spectrum β-Lactamases and Serine Carbapenemases
Microbiological Characterization of VNRX-5236, a Broad-Spectrum β-Lactamase Inhibitor for Rescue of the Orally Bioavailable Cephalosporin Ceftibuten as a Carbapenem-Sparing Agent against Strains of <i>Enterobacterales</i> Expressing Extended-Spectrum β-Lactamases and Serine Carbapenemases Open
There is an urgent need for oral agents to combat resistant Gram-negative pathogens. Here, we describe the characterization of VNRX-5236, a broad-spectrum boronic acid β-lactamase inhibitor (BLI), and its orally bioavailable etzadroxil pro…
View article: Oral Immunotherapy With Human Secretory Immunoglobulin A Improves Survival in the Hamster Model of <i>Clostridioides difficile</i> Infection
Oral Immunotherapy With Human Secretory Immunoglobulin A Improves Survival in the Hamster Model of <i>Clostridioides difficile</i> Infection Open
Coadministration of human secretory IgA (sIgA) together with subtherapeutic vancomycin enhanced survival in the Clostridioides difficile infection (CDI) hamster model. Vancomycin (5 or 10 mg/kg × 5 days) plus healthy donor plasma sIgA/mono…
View article: 1272. Efficacy of a Non-Peptide, Small Molecule Mimic of Host Defense Proteins in Mouse Models of Disseminated Candidiasis and Aspergillosis
1272. Efficacy of a Non-Peptide, Small Molecule Mimic of Host Defense Proteins in Mouse Models of Disseminated Candidiasis and Aspergillosis Open
Background We are developing a series of small nonpeptide mimics of host defense proteins (smHDPs) for antifungal applications. MICs < 0.1 µg/ ml have been demonstrated against multiple yeast and mold species. Their potential therapeuti…
View article: Epidemic ribotypes of Clostridium (now Clostridioides) difficile are likely to be more virulent than non-epidemic ribotypes in animal models
Epidemic ribotypes of Clostridium (now Clostridioides) difficile are likely to be more virulent than non-epidemic ribotypes in animal models Open
Background Clostridioides difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the inc…
View article: EPIDEMIC RIBOTYPES OF CLOSTRIDIUM (NOW CLOSTRIDIOIDES) DIFFICILE ARE LIKELY TO BE MORE VIRULENT THAN NON-EPIDEMIC RIBOTYPES IN ANIMAL MODELS
EPIDEMIC RIBOTYPES OF CLOSTRIDIUM (NOW CLOSTRIDIOIDES) DIFFICILE ARE LIKELY TO BE MORE VIRULENT THAN NON-EPIDEMIC RIBOTYPES IN ANIMAL MODELS Open
Background . Clostridioides difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the i…
View article: Epidemic Ribotypes Of Clostridium (Now Clostridioides) Difficile Are Likely To Be More Virulent Than Non-Epidemic Ribotypes In Animal Models
Epidemic Ribotypes Of Clostridium (Now Clostridioides) Difficile Are Likely To Be More Virulent Than Non-Epidemic Ribotypes In Animal Models Open
Background: Clostridioides difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the in…
View article: DAV131A Protects Hamsters from Lethal <i>Clostridioides difficile</i> Infection Induced by Fluoroquinolones
DAV131A Protects Hamsters from Lethal <i>Clostridioides difficile</i> Infection Induced by Fluoroquinolones Open
Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota, resulting in loss of resistance to colonization by exogenous bacteria such as Clostridioides difficile that may cause severe diarrhea in humans and lethal infection …
View article: Epidemic Ribotypes Of Clostridium (Now Clostridioides) Difficile Are Likely To Be More Virulent Than Non-epidemic Ribotypes In Animal Models
Epidemic Ribotypes Of Clostridium (Now Clostridioides) Difficile Are Likely To Be More Virulent Than Non-epidemic Ribotypes In Animal Models Open
Background. Clostridium difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the incre…
View article: Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region
Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region Open
C. difficile is an endospore-forming pathogen, which is becoming a common cause of microbial health-care associated gastrointestinal disease in the United States. Both healthy and symptomatic patients can shed C. difficile spores into the …
View article: Treatment and Prevention of Recurrent Clostridium difficile Infection with Functionalized Bovine Antibody-Enriched Whey in a Hamster Primary Infection Model
Treatment and Prevention of Recurrent Clostridium difficile Infection with Functionalized Bovine Antibody-Enriched Whey in a Hamster Primary Infection Model Open
Toxin-induced Clostridium difficile infection (CDI) is a major disease characterized by severe diarrhea and high morbidity rates. The aim with this study was to develop an alternative drug for the treatment of CDI. Cows were repeatedly imm…
View article: Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment of <i>Clostridium difficile</i> -Associated Infection
Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment of <i>Clostridium difficile</i> -Associated Infection Open
Lantibiotics present an attractive scaffold for the development of novel antibiotics. We report here a novel lantibiotic for the treatment of Clostridium difficile infection.
View article: <i>In Vivo</i> Efficacy of Novel Monobactam LYS228 in Murine Models of Carbapenemase-Producing <i>Klebsiella pneumoniae</i> Infection
<i>In Vivo</i> Efficacy of Novel Monobactam LYS228 in Murine Models of Carbapenemase-Producing <i>Klebsiella pneumoniae</i> Infection Open
LYS228 has potent antibacterial activity against carbapenem-resistant strains of Enterobacteriaceae . LYS228 was efficacious in neutropenic thigh models established with Klebsiella pneumoniae producing KPC-2 or NDM-1; pretreatment with ura…
View article: Clostridium (Now Closteroides) difficile Spore Formation Is Higher in Epidemic Isolates When Treated With Vancomycin in Vivo and in Vitro
Clostridium (Now Closteroides) difficile Spore Formation Is Higher in Epidemic Isolates When Treated With Vancomycin in Vivo and in Vitro Open
Between 2000-2007, Clostridium (now Closteroides) difficile infections have increased by a factor of 400% and have been associated with greater disease severity. These increases are associated to the increased prevalence of the NAP1/BI/027…
View article: Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection
Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection Open
Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile . Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrati…
OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections Open
Lantibiotics continue to offer an untapped pipeline for the development of novel antibiotics. We report here the discovery of a novel lantibiotic for the treatment of C. difficile infection (CDI). The leads were selected from a library of …
View article: Antibiotic-induced dysbiosis predicts mortality in an animal model of<i>Clostridium difficile</i>infection
Antibiotic-induced dysbiosis predicts mortality in an animal model of<i>Clostridium difficile</i>infection Open
Background Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile . Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic …
View article: Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection
Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection Open
Lantibiotics offer an untapped pipeline for the development of novel antibiotics to treat serious Gram-positive (+) infections including Clostridium difficile. Mutacin 1140 (MU1140) is a lantibiotic produced by Streptococcus mutans and act…