A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria
A number of pathogenic bacteria reproduce inside mammalian cells and are thus inaccessible to many antimicrobial drugs. Herein, we present a facile method to a focused library of antibacterial agents known as cationic amphiphilic polyproline helices (CAPHs). We identified three CAPHs from the librar...
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Published in | ACS infectious diseases Vol. 4; no. 9; pp. 1300 - 1305 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
14.09.2018
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Subjects | |
Online Access | Get full text |
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Abstract | A number of pathogenic bacteria reproduce inside mammalian cells and are thus inaccessible to many antimicrobial drugs. Herein, we present a facile method to a focused library of antibacterial agents known as cationic amphiphilic polyproline helices (CAPHs). We identified three CAPHs from the library with superior cell penetration within macrophages and excellent antibacterial action against both Gram-positive and Gram-negative bacteria. These cell-penetrating antibacterial CAPHs have specific subcellular localizations that allow for targeting of pathogenic bacteria at their intracellular niches, a unique feature that promotes the successful clearance of intracellular pathogens (Salmonella, Shigella, and Listeria) residing within macrophages. Furthermore, the selected CAPHs also significantly reduced bacterial infections in an in vivo model of Caenorhabditis elegans, with minimal in vivo toxicity. |
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AbstractList | A number of pathogenic bacteria reproduce inside mammalian cells and are thus inaccessible to many antimicrobial drugs. Herein, we present a facile method to a focused library of antibacterial agents known as cationic amphiphilic polyproline helices (CAPHs). We identified three CAPHs from the library with superior cell penetration within macrophages and excellent antibacterial action against both Gram-positive and Gram-negative bacteria. These cell-penetrating antibacterial CAPHs have specific subcellular localizations that allow for targeting of pathogenic bacteria at their intracellular niches, a unique feature that promotes the successful clearance of intracellular pathogens (Salmonella, Shigella, and Listeria) residing within macrophages. Furthermore, the selected CAPHs also significantly reduced bacterial infections in an in vivo model of Caenorhabditis elegans, with minimal in vivo toxicity. |
Author | Nepal, Manish Chmielewski, Jean Eldesouky, Hassan E. Mohamed, Mohamed F. Blade, Reena Seleem, Mohamed N. N. Anderson, Tiffany |
AuthorAffiliation | Department of Chemistry Purdue University Department of Comparative Pathobiology |
AuthorAffiliation_xml | – name: Department of Chemistry – name: Purdue University – name: Department of Comparative Pathobiology |
Author_xml | – sequence: 1 givenname: Manish surname: Nepal fullname: Nepal, Manish organization: Department of Chemistry – sequence: 2 givenname: Mohamed F. surname: Mohamed fullname: Mohamed, Mohamed F. organization: Purdue University – sequence: 3 givenname: Reena surname: Blade fullname: Blade, Reena organization: Department of Chemistry – sequence: 4 givenname: Hassan E. surname: Eldesouky fullname: Eldesouky, Hassan E. organization: Purdue University – sequence: 5 givenname: Tiffany surname: N. Anderson fullname: N. Anderson, Tiffany organization: Department of Chemistry – sequence: 6 givenname: Mohamed N. orcidid: 0000-0003-0939-0458 surname: Seleem fullname: Seleem, Mohamed N. organization: Purdue University – sequence: 7 givenname: Jean orcidid: 0000-0003-4958-7175 surname: Chmielewski fullname: Chmielewski, Jean email: chml@purdue.edu organization: Department of Chemistry |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29979033$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1016_j_copbio_2019_05_006 crossref_primary_10_1021_acs_biochem_9b00857 crossref_primary_10_1021_acsinfecdis_0c00547 crossref_primary_10_1002_pep2_24224 crossref_primary_10_1111_cbdd_13930 crossref_primary_10_3390_antibiotics11121772 crossref_primary_10_1016_j_biomaterials_2019_119249 crossref_primary_10_1021_acs_joc_0c00871 |
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Title | A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria |
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