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Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials

Zhang, Liangchen ; Fan, Yaxun ; Galantini, Luciano ; Schillén, Karin LU orcid ; Del Giudice, Alessandra ; Du, Guanqun LU and Wang, Yilin (2023) In Langmuir 39(1). p.495-506
Abstract
New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against S. aureus become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products,... (More)
New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against S. aureus become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products, exhibits the best antibacterial activity but the lowest cytotoxicity and the weakest skin irritation. All CA/polyamines and DCA/polyamines form well-ordered ribbon-like aggregates, collecting numerous facial amphiphilic structures to significantly enhance the interactions with bacterial membranes. In particular, the biogenic polyamines with more than two amine groups provide extra positively charged sites, hence facilitating the binding of bile acid oligomers to the negatively charged outer membrane of the bacteria via electrostatic interaction. This in turn promotes more oligomeric bile acid units that can be inserted into the membrane through hydrophobic interaction between bile acids and lipid domains. The noncovalently constructed and separable amphiphilic antimicrobials can avoid the long-term coexistence of microorganisms and antibacterial molecules in different acting modes. Therefore, the noncovalent bile acid oligomers, especially those with higher oligomerization degrees, can be a potential approach to effectively enhance antibacterial activity, improve environmental friendliness, and reduce bacterial drug resistance. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Langmuir
volume
39
issue
1
pages
12 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:36529944
  • scopus:85144357903
ISSN
0743-7463
DOI
10.1021/acs.langmuir.2c02787
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 American Chemical Society.
id
540d8ef0-c9e7-4a46-b25b-971a2490375f
date added to LUP
2023-01-04 07:43:33
date last changed
2024-05-02 18:38:19
@article{540d8ef0-c9e7-4a46-b25b-971a2490375f,
  abstract     = {{New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against <i>S. aureus</i> become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products, exhibits the best antibacterial activity but the lowest cytotoxicity and the weakest skin irritation. All CA/polyamines and DCA/polyamines form well-ordered ribbon-like aggregates, collecting numerous facial amphiphilic structures to significantly enhance the interactions with bacterial membranes. In particular, the biogenic polyamines with more than two amine groups provide extra positively charged sites, hence facilitating the binding of bile acid oligomers to the negatively charged outer membrane of the bacteria via electrostatic interaction. This in turn promotes more oligomeric bile acid units that can be inserted into the membrane through hydrophobic interaction between bile acids and lipid domains. The noncovalently constructed and separable amphiphilic antimicrobials can avoid the long-term coexistence of microorganisms and antibacterial molecules in different acting modes. Therefore, the noncovalent bile acid oligomers, especially those with higher oligomerization degrees, can be a potential approach to effectively enhance antibacterial activity, improve environmental friendliness, and reduce bacterial drug resistance.}},
  author       = {{Zhang, Liangchen and Fan, Yaxun and Galantini, Luciano and Schillén, Karin and Del Giudice, Alessandra and Du, Guanqun and Wang, Yilin}},
  issn         = {{0743-7463}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{495--506}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Langmuir}},
  title        = {{Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials}},
  url          = {{http://dx.doi.org/10.1021/acs.langmuir.2c02787}},
  doi          = {{10.1021/acs.langmuir.2c02787}},
  volume       = {{39}},
  year         = {{2023}},
}