Abstract:Bacterial infections have become a global issue that requires urgent attention, particularly regarding to emergence of multidrug resistant bacteria. We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain. Interestingly, by choosing appropriate monomers, these cationic polymers can form core-shell micelles. These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species. It is demonst… Show more
“…Bile is a type of secretion produced naturally by mammals and other vertebrates ( Table 1 ) [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. This fluid is rich in bile acids, which are aliphatic molecules that are conjugated in the liver with taurine or glycine.…”
Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.
“…Bile is a type of secretion produced naturally by mammals and other vertebrates ( Table 1 ) [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. This fluid is rich in bile acids, which are aliphatic molecules that are conjugated in the liver with taurine or glycine.…”
Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.
“…Many antimicrobial polymers are highly effective in killing traditional strains. We have developed several antimicrobial macromolecules utilizing bulky hydrophobic structures containing natural resin acids and antibiotic-metal bioconjugates that exhibit excellent activities against bacteria, particularly against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), while simultaneously exhibiting low hemolysis against red blood cells and minimal in vitro and in vivo cytotoxicity 27 – 35 . Fig.…”
Section: Introductionmentioning
confidence: 99%
“…Bile acids are cholesterol-derived amphiphilic steroid acids produced in mammals and other vertebrates. They have been utilized in many areas including drug delivery, sensors, polymeric gels, antimicrobials, and other biological applications 35 , 42 – 44 . There are four different derivatives of bile acids, which vary by the number of hydroxyl groups, such as cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid, and lithocholic acid (LCA) (Supplementary Figure 1a ).…”
Bacterial infections and antibiotic resistance, particularly by Gram-negative pathogens, have become a global healthcare crisis. We report the design of a class of cationic antimicrobial polymers that cluster local facial amphiphilicity from repeating units to enhance interactions with bacterial membranes without requiring a globally conformational arrangement associated with highly unfavorable entropic loss. This concept of macromolecular architectures is demonstrated with a series of multicyclic natural product-based cationic polymers. We have shown that cholic acid derivatives with three charged head groups are more potent and selective than lithocholic and deoxycholic counterparts, particularly against Gram-negative bacteria. This is ascribed to the formation of true facial amphiphilicity with hydrophilic ion groups oriented on one face and hydrophobic multicyclic hydrocarbon structures on the opposite face. Such local facial amphiphilicity is clustered via a flexible macromolecular backbone in a concerted way when in contact with bacterial membranes.
“…This effect was also highlighted before in solution leading, in some cases, to the formation of micelles. [ 42,53 ] Further evaluation of these conformations using reflectivity scattering techniques (X‐rays and neutrons) are currently under progress.…”
Polyionenes (PI) with stable positive charges and tunable hydrophobic spacers in the polymer backbone, are shown to be particularly efficient regarding antimicrobial properties. This effect can be modulated since it increases with the length of hydrophobic spacers, i.e., the number of methylene groups between quaternary ammoniums. Now, to further explore these properties and provide efficient antimicrobial surfaces, polyionenes should be grafted onto materials. Here a robust grafting strategy to covalently attach polyionenes is described. The method consisted in a sequential surface chemistry procedure combining polydopamine coating, diazonium-induced polymerization, and polyaddition. To the best of knowledge, grafting of PI onto surfaces is not reported earlier. All chemical steps are characterized in detail via various surface analysis techniques (FTIR, X-ray photoelectron spectroscopy, contact angle, and surface energy measurements). The antibacterial properties of polyionene-grafted surfaces are then studied through bacterial adhesion experiments consisting in enumeration of adherent bacteria (total and viable cultivable cells). PI-grafted surfaces are showed to display effective and versatile bacteriostatic/bactericidal properties associated with a proadhesive effect.
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