Constance M John1,2, Min Li1,2, Dongxiao Feng1, Gary A Jarvis1,2. 1. Center for Immunochemistry, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, USA. 2. Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
Abstract
OBJECTIVES: Cell-penetrating peptides (CPPs) have been evaluated for intracellular delivery of molecules and several CPPs have bactericidal activity. Our objectives were to determine the effect of a 12 amino acid CPPs on survival and on the invasive and inflammatory potential of Neisseria gonorrhoeae. METHODS: Survival of MDR and human challenge strains of N. gonorrhoeae grown in cell culture medium with 10% FBS was determined after treatment with the CPP and human antimicrobial peptide LL-37 for 4 h. Confocal microscopy was used to examine penetration of FITC-labelled CPP into bacterial cells. The ability of the CPP to prevent invasion of human ME-180 cervical epithelial cells and to reduce the induction of TNF-α in human THP-1 monocytic cells in response to gonococcal infection was assessed. Cytotoxicity of the CPP towards the THP-1 cells was determined. RESULTS: The CPP was bactericidal, with 95%-100% killing of all gonococcal strains at 100 μM. Confocal microscopy of gonococci incubated with FITC-labelled CPP revealed the penetration of the peptide. CPP treatment of N. gonorrhoeae inhibited gonococcal invasion of ME-180 cells and reduced the expression of TNF-α induced in THP-1 cells by gonococci. The CPP showed no cytotoxicity towards human THP-1 cells. CONCLUSIONS: Based on these promising results, future studies will focus on testing of CPP in the presence of other types of host cells and exploration of structural modifications of the CPP that could decrease its susceptibility to proteolysis and increase its potency. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2019. This work is written by US Government employees and is in the public domain in the US.
OBJECTIVES: Cell-penetrating peptides (CPPs) have been evaluated for intracellular delivery of molecules and several CPPs have bactericidal activity. Our objectives were to determine the effect of a 12 amino acid CPPs on survival and on the invasive and inflammatory potential of Neisseria gonorrhoeae. METHODS: Survival of MDR and human challenge strains of N. gonorrhoeae grown in cell culture medium with 10% FBS was determined after treatment with the CPP and human antimicrobial peptide LL-37 for 4 h. Confocal microscopy was used to examine penetration of FITC-labelled CPP into bacterial cells. The ability of the CPP to prevent invasion of human ME-180 cervical epithelial cells and to reduce the induction of TNF-α in human THP-1 monocytic cells in response to gonococcal infection was assessed. Cytotoxicity of the CPP towards the THP-1 cells was determined. RESULTS: The CPP was bactericidal, with 95%-100% killing of all gonococcal strains at 100 μM. Confocal microscopy of gonococci incubated with FITC-labelled CPP revealed the penetration of the peptide. CPP treatment of N. gonorrhoeae inhibited gonococcal invasion of ME-180 cells and reduced the expression of TNF-α induced in THP-1 cells by gonococci. The CPP showed no cytotoxicity towards human THP-1 cells. CONCLUSIONS: Based on these promising results, future studies will focus on testing of CPP in the presence of other types of host cells and exploration of structural modifications of the CPP that could decrease its susceptibility to proteolysis and increase its potency. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2019. This work is written by US Government employees and is in the public domain in the US.
Authors: Ewerton Cristhian Lima de Oliveira; Kauê Santana; Luiz Josino; Anderson Henrique Lima E Lima; Claudomiro de Souza de Sales Júnior Journal: Sci Rep Date: 2021-04-07 Impact factor: 4.379
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