Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials

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, 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.

Influence of Immobilization Strategies on the Antibacterial Properties of Antimicrobial Peptide-Chitosan Coatings

“…Thus, it comes as no surprise that a number of strategies have been emerging to develop antimicrobial surfaces, either by preventing protein adsorption (anti-fouling surfaces) or cell adhesion (anti-adhesive surfaces) or by killing bacteria (bactericidal surfaces) [3,4]. A few examples are cationic compounds [5], quorum-sensing inhibitors [6], and antimicrobial peptide-based approaches. Cationic compounds, such as polyamines or quaternary ammonium compounds [7], can interact with bacterial membranes, leading to membrane destabilization.…”

Acanthoscurria gomesiana spider‐derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

“…Polyamines have been widely studied in many pathophysiological conditions, including those polyamines related to antimicrobial [1] and anticancer [2] agents, cardiovascular disorders, [3] hepatic dysfunction, [4] chronic and neuropathic pain, [5,6] and inflammation. [7] Moreover, it has been observed that polyamines interact with glutamatergic receptors, particularly ionotropic receptors, acting either as antagonists or modulators of these receptors.…”