A5025441513- Antibiotics Pharmacokinetics and Efficacy
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- Pneumonia and Respiratory Infections
- Bacterial biofilms and quorum sensing
- Cancer therapeutics and mechanisms
- Clostridium difficile and Clostridium perfringens research
- Antifungal resistance and susceptibility
- Bacteriophages and microbial interactions
- Bioactive Compounds and Antitumor Agents
- Bacterial Genetics and Biotechnology
- Metal complexes synthesis and properties
- Synthesis and Biological Evaluation
- Fungal Plant Pathogen Control
- Antimicrobial Peptides and Activities
- Toxin Mechanisms and Immunotoxins
- Bacillus and Francisella bacterial research
- Advanced Drug Delivery Systems
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Synthesis and Reactions of Organic Compounds
- Pneumocystis jirovecii pneumonia detection and treatment
- Boron Compounds in Chemistry
- Immune Response and Inflammation
- Yersinia bacterium, plague, ectoparasites research
GlaxoSmithKline (United States)
2022-2024
Janssen (United States)
2014-2022
AstraZeneca (United States)
2019-2020
Springhouse
2014
Johnson & Johnson (United States)
1990-2010
Rutgers, The State University of New Jersey
1998
University of California, Los Angeles
1952
A new antibody platform combining anti-Psl and anti-PcrV activities provides enhanced protection acts synergistically with antibiotics against Pseudomonas aeruginosa .
ABSTRACT Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus . We previously identified monoclonal antibody (MAb) against AT that reduced severity mouse dermonecrosis model. Here, we evaluate activity an affinity-optimized variant, LC10, model S. pneumonia. Passive immunization with LC10 increased survival and bacterial numbers lungs kidneys infected mice showed protection diverse clinical isolates. The -infected exhibited pneumonia, including...
S. aureus α toxin promotes opportunistic co-infection, which can be neutralized with a pathogen-specific antibody.
Candida albicans and Staphylococcus aureus are among the most prevalent nosocomial pathogens that responsible for severe morbidity mortality, even with appropriate treatment. Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown coinfection these results in synergistic lethality is partially dependent on exacerbated prostaglandin signaling, while monomicrobial nonlethal. Therefore, objective this study was to identify staphylococcal virulence...
ABSTRACT Many pathogenic bacteria utilize two-component systems consisting of a histidine protein kinase (HPK) and response regulator (RR) for signal transduction. During the search novel inhibitors, several chemical series, including benzoxazines, benzimidazoles, bis-phenols, cyclohexenes, trityls, salicylanilides, were identified that inhibited purified HPK-RR pairs KinA-Spo0F NR II -NR I , with 50% inhibitory concentrations (IC 50 s) ranging from 1.9 to >500 μM MICs 0.5 >16 μg/ml...
An optimal host response against Staphylococcus aureus skin and soft tissue infections (SSTI) is dependent on IL-1β IL-17 mediated abscess formation. Alpha toxin (AT), an essential virulence factor for SSTI, has been reported to damage integrity; however its effect the immune not investigated. Here, we demonstrate that infection with USA300 AT isogenic mutant (Δhla), or passive immunization neutralizing mAb, 2A3, 24 h prior wild type (WT), resulted in dermonecrotic lesion size reduction,...
Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. pneumonia; however, effects MAb in immunocompromised have not been reported. In this study, passive immunization survival rates and reduced bacterial numbers lungs an murine pneumonia model. Lungs infected exhibited alveolar epithelial damage, protein leakage, overgrowth, whereas passively immunized...
Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. disease mouse dermonecrosis model by neutralizing AT-mediated necrosis immune evasion. In the present study, MEDI4893*, affinity-optimized version was characterized for therapeutic activity as single agent combination with two frontline antibiotics,...
The role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on healthy microbiome, has led to advances pathogen-specific approaches for prevention or treatment serious bacterial infections. One approach clinical testing is passive immunization a monoclonal antibody (MAb) targeting alpha toxin Staphylococcus aureus pneumonia. Passive human anti-alpha MAb, MEDI4893*, been shown improve disease outcome murine S. pneumonia models. species...
Methicillin-resistant Staphylococcus aureus (MRSA) causes large-scale epidemics of acute bacterial skin and structure infections (ABSSSI) within communities across the United States. Animal models that reproduce ABSSSI as they occur in humans are urgently needed to test new therapeutic strategies. Alpha-toxin plays a critical role variety staphylococcal infection mice, but its pathogenesis remains be elucidated rabbits, which similar their susceptibility S. superantigens certain bicomponent...
ABSTRACT Bacillus anthracis is a Gram-positive Centers for Disease Control and Prevention category “A” biothreat pathogen. Without early treatment, inhalation of anthrax spores with progression to inhalational disease associated high fatality rates. Gepotidacin novel first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by distinct mechanism action being evaluated use against conventional pathogens. selectively via unique binding mode has in vitro activity...
Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F. can cause pneumonia and respiratory failure associated with high mortality rates without early treatment. Gepotidacin novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by distinct mechanism action. selectively via unique binding mode, has activity against multidrug-resistant target pathogens, demonstrated
The in vivo efficacy of JNJ-Q2, a new broad-spectrum fluoroquinolone (FQ), was evaluated murine septicemia model with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. (MRSA) Streptococcus pneumoniae lower respiratory tract infection model. JNJ-Q2 comparators were also an acute skin using community-acquired MRSA strain established (ESI) hospital-acquired strain, for which the selection resistant mutants determined. demonstrated activity MSSA that comparable to...
Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through unique binding mode has the potential to treat number of diseases. Development this new pneumonic plague caused by Yersinia pestis depends on U.S. Food Drug Administration Animal Rule testing pathway, as in humans not feasible. Here, preclinical studies were conducted African green monkey (AGM) inhalational model test efficacy gepotidacin. AGMs...
The bacteriophage T4 PinA protein inhibited degradation of [<sup>3</sup>H]α-methyl casein by purified Lon protease from <i>Escherichia coli</i>, but inhibition was noncompetitive with respect to casein. did not inhibit cleavage the fluorogenic peptide,<i>N</i>-glutaryl-alanylalanylphenylalanyl-3-methoxynaphthylamide and, moreover, block ability substrates, such as casein, activate peptides Lon. Thus, does proteolytic active site or allosteric protein-binding on Inhibition basal ATPase...
Doripenem is a carbapenem with potent broad-spectrum activity against Gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. As the incidence of extended-spectrum β-lactamase (ESBL)-producing bacilli increasing, it was interest to examine in vivo comparative efficacy doripenem, imipenem, and meropenem Klebsiella pneumoniae isolate expressing TEM-26 ESBL enzyme. In murine lethal lower respiratory infection model, doripenem reduced lung burden by 2 log(10) CFU/g tissue...
Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in subcutaneous skin infection model Smith OC 4172 (methicillin-susceptible S. [MSSA]), 8525 (MRSA), Pseudomonas aeruginosa 4351 (having an inducible AmpC beta-lactamase), and P. 4354 (overproducing beta-lactamase). In the MSSA MRSA models, ceftobiprole, administered as prodrug ceftobiprole...
Antibiotics revolutionized the treatment of infectious diseases; however, it is now clear that broad-spectrum antibiotics alter composition and function host's microbiome. The microbiome plays a key role in human health, its perturbation increasingly recognized as contributing to many diseases. Widespread antibiotic use has also resulted emergence multidrug-resistant pathogens, spurring development pathogen-specific strategies such monoclonal antibodies (MAbs) combat bacterial infection. Not...