ArticleAntimicrobial agents and chemotherapy2016
Staphylococcus aureus Alpha-Toxin Is Conserved among Diverse Hospital Respiratory Isolates Collected from a Global Surveillance Study and Is Neutralized by Monoclonal Antibody MEDI4893.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults.Antimicrobial agents and chemotherapy · 2017Trial
- Multivalent nanobodies for potent and broad neutralization of Staphylococcus aureus toxins.Nature communications · 2026Article
- Adeno-associated virus delivery of anti-alpha toxin monoclonal antibodies confers protection against Staphylococcus aureus infections.PLoS pathogens · 2026Article
- Structure of ClfA002 in Complex With Neutralizing Antibody AZD7745 Provides Insight into Its Broad Neutralization Mechanism in Staphylococcus aureus Infection.The Journal of infectious diseases · 2025Article
- Utilization of probiotics against virulence factors of Staphylococcus aureus in bovine mastitis.Antonie van Leeuwenhoek · 2025Review
- The virulence toolkit of Staphylococcus aureus: a comprehensive review of toxin diversity, molecular mechanisms, and clinical implications.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Review
- Antibody-based alternatives to animal testing for toxin detection and antitoxin evaluation.Frontiers in toxicology · 2025Review
- Article
- Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair.International journal of molecular sciences · 2024Review
- In Vivo Detection ofInternational journal of biomedical imaging · 2024Article
- Treatment of MRSA Infection: Where are We?Current medicinal chemistry · 2024Review
- Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes ofJournal of Korean medical science · 2023Article
- Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants.Microbiology spectrum · 2023Article
- Virulence genes and antibiotic resistance profiles ofIranian journal of veterinary research · 2023Article
- Inhibition of α-hemolysin activity of Staphylococcus aureus by theaflavin 3,3'-digallate.PloS one · 2023Article
- Identification of two neutralizing human single-chain variable fragment antibodies targetingIranian journal of basic medical sciences · 2022Article
- Review
- Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections.Antibiotics (Basel, Switzerland) · 2022Review
- Methicillin-Resistant Staphylococcus aureus Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia.Seminars in respiratory and critical care medicine · 2022Article
- SensitizingeLife · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staphylococcus aureus infections lead to an array of illnesses ranging from mild skin infections to serious diseases, such endocarditis, osteomyelitis, and pneumonia. Alpha-toxin (Hla) is a pore-forming toxin, encoded by the hla gene, that is thought to play a key role in S. aureus pathogenesis. A monoclonal antibody targeting Hla, MEDI4893, is in clinical development for the prevention of S. aureus ventilator-associated pneumonia (VAP). The presence of the hla gene and Hla protein in 994 respiratory isolates collected from patients in 34 countries in Asia, Europe, the United States, Latin America, the Middle East, Africa, and Australia was determined. Hla levels were correlated with the geographic location, age of the subject, and length of stay in the hospital. hla gene sequence analysis was performed, and mutations were mapped to the Hla crystal structure. S. aureus supernatants containing Hla variants were tested for susceptibility or resistance to MEDI4893. The hla gene was present and Hla was expressed in 99.0% and 83.2% of the isolates, respectively, regardless of geographic region, hospital locale, or age of the subject. More methicillin-susceptible than methicillin-resistant isolates expressed Hla (86.9% versus 78.8%; P = 0.0007), and S. aureus isolates from pediatric patients expressed the largest amounts of Hla. Fifty-seven different Hla subtypes were identified, and 91% of the isolates encoded an Hla subtype that was neutralized by MED4893. This study demonstrates that Hla is conserved in diverse S. aureus isolates from around the world and is an attractive target for prophylactic monoclonal antibody (MAb) or vaccine development.
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