Abstract
Preventing the adhesion of pathogens to host cells provides an innovative approach to tackling multidrug-resistant bacteria. In this regard, the identification of outer membrane protein A (OmpA) as a key bacterial virulence factor has been a major breakthrough. The use of virtual screening helped us to identify a cyclic hexapeptide AOA-2 that inhibits the adhesion of Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli to host cells and the formation of biofilm, thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. Inhibition of OmpA offers a strategy as monotherapy to address the urgent need for treatments for infections caused by Gram-negative bacilli.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acinetobacter Infections / drug therapy
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Acinetobacter Infections / immunology*
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Acinetobacter baumannii / physiology*
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Alveolar Epithelial Cells / physiology*
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Animals
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Anti-Bacterial Agents / therapeutic use
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Bacterial Adhesion / drug effects*
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Bacterial Outer Membrane Proteins / antagonists & inhibitors*
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Biofilms
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Cell Line
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DNA Helicases
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Disease Models, Animal
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Escherichia coli / physiology*
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Escherichia coli Infections / drug therapy
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Escherichia coli Infections / immunology*
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Female
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Humans
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Mice
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Mice, Inbred C57BL
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Multifunctional Enzymes
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Peptides / genetics
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Peptides / metabolism*
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Peptides / therapeutic use
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Pseudomonas Infections / drug therapy
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Pseudomonas Infections / immunology*
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Pseudomonas aeruginosa / physiology*
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RNA Helicases / genetics
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RNA Helicases / metabolism*
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RNA Helicases / therapeutic use
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Sepsis / immunology*
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Virulence Factors / antagonists & inhibitors*
Substances
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Anti-Bacterial Agents
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Bacterial Outer Membrane Proteins
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Multifunctional Enzymes
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Peptides
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Virulence Factors
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OMPA outer membrane proteins
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SETX protein, human
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DNA Helicases
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RNA Helicases