Effective antibacterial action of tat (47-58) by increased uptake into bacterial cells in the presence of trypsin.
In a previous study, we found an antifungal effect on human pathogenic fungi by the cell-penetrating peptide Tat (47-58) derived from HIV-1. Tat (47-58) immediately entered into the fungal nucleus and affected some physiological changes on the intracellular condition. In this study, Tat (47-58) showed a broad spectrum of antibacterial activity against pathogenic bacteria including bacterial clinical isolates. To improve resistance against proteases for use in vivo, we synthesized an analog of Tat (47-58) by substituting the L-amino acid for the D-amino acid. The D-enantiomer of Tat (47-58) also exhibited a broad spectrum of antibacterial activity at almost the same level of L-Tat (47-58) concentration. Unlike L-Tat (47-58), D-Tat (47-58) showed a significant proteolytic resistance against all proteases tested and antimicrobial activities in the presence of trypsin. Moreover, D-Tat (47-58) inhibited MRSA infection in human HeLa cells whereas L-Tat (47-58) partially allowed MRSA infection, and the results were due to the proteolytic resistance of D-Tat (47-58).
Jung
Hyun Jun
HJ
Department of Microbiology, College of Natural Sciences,Kyungpook National University, Daegu 702-701, Korea.
Jeong
Kyu-Shik
KS
Lee
Dong Gun
DG
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D024881:Drug Resistance, Bacterial; D004912:Erythrocytes / Q000187:drug effects; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D016106:Methicillin Resistance; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D014357:Trypsin / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C511652:tat peptide (47-58), Human immunodeficiency virus 1; D014357:Trypsin