ArticlePloS one2013
Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Segment-Based Peptide Design Reveals the Importance of N-Terminal High Cationicity for Antimicrobial Activity Against Gram-Negative Pathogens.Probiotics and antimicrobial proteins · 2025Article
- Antimicrobial Peptides (AMPs) and the Microbiome in Preterm Infants: Consequences and Opportunities for Future Therapeutics.International journal of molecular sciences · 2024Review
- HAMLET, a human milk protein-lipid complex, modulates amoxicillin induced changes in anFrontiers in microbiology · 2024Article
- Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses.Antibiotics (Basel, Switzerland) · 2023Article
- Unveiling the Antibiotic Susceptibility and Antimicrobial Potential of Bacteria from Human Breast Milk of Pakistani Women: An Exploratory Study.BioMed research international · 2023Article
- Role of serotype and virulence determinants ofFrontiers in cellular and infection microbiology · 2023Article
- Bayesian Modeling and Intrabacterial Drug Metabolism Applied to Drug-ResistantACS infectious diseases · 2021Article
- Short and Robust Anti-Infective Lipopeptides Engineered Based on the Minimal Antimicrobial Peptide KR12 of Human LL-37.ACS infectious diseases · 2021Article
- Accelerative Effect of Cinnamon Nanoparticles as well as HAMLET on Healing of Wounds Infected with MRSA in Diabetic Rats.BioMed research international · 2021Article
- Antimicrobial Activities of Alginate and Chitosan Oligosaccharides AgainstFrontiers in microbiology · 2021Article
- Can breastfeeding protect against antimicrobial resistance?BMC medicine · 2020Article
- A bacteriocin-based antimicrobial formulation to effectively disrupt the cell viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.NPJ biofilms and microbiomes · 2020Article
- Sequence Permutation Generates Peptides with Different Antimicrobial and Antibiofilm Activities.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Re-sensitizing Ampicillin and Kanamycin-ResistantFrontiers in bioengineering and biotechnology · 2020Article
- The Demand for New Antibiotics: Antimicrobial Peptides, Nanoparticles, and Combinatorial Therapies as Future Strategies in Antibacterial Agent Design.Frontiers in microbiology · 2020Review
- The human milk protein-lipid complex HAMLET disrupts glycolysis and induces death inThe Journal of biological chemistry · 2019Article
- Protein-lipid complexes: molecular structure, current scenarios and mechanisms of cytotoxicity.RSC advances · 2019Review
- HAMLET, a protein complex from human milk has bactericidal activity and enhances the activity of antibiotics against pathogenicAntimicrobial agents and chemotherapy · 2019Article
- Modulation of antimicrobial potency of human cathelicidin peptides against the ESKAPE pathogens and in vivo efficacy in a murine catheter-associated biofilm model.Biochimica et biophysica acta. Biomembranes · 2019Article
- Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus.Metallomics : integrated biometal science · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.