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Specific localisation of ions in bacterial membranes unravels physical mechanism of effective bacteria killing by sanitiser.

ABSTRACT: Antimicrobial resistance is a major threat to public health. Although many commercial sanitisers contain a combination of cationic surfactants and aromatic alcohols, the physical mechanisms where these two substances bind to or how they disturb bacterial membranes are still largely unknown. In this study, we designed a well-defined model of Gram-negative bacteria surfaces based on the monolayer of lipopolysaccharides with uniform saccharide head groups. Since commonly used X-ray reflectivity is sensitive to changes in the thickness, roughness and electron density but is not sensitive to elements, we employed grazing incidence X-ray fluorescence. In the absence of Ca²⁺, cationic surfactants can penetrate into the membrane core with no extra support by disturbing the layer of K⁺ coupled to negatively charged saccharide head group at z?=?17 Å from the air/chain interface. On the other hand, Ca²⁺ confined at z?=?19 Å crosslink charged saccharides and prevent the incorporation of cationic surfactants. We found that the addition of nonlethal aromatic alcohols facilitate the incorporation of cationic surfactants by the significant roughening of the chain/saccharide interface. Combination of precise localisation of ions and molecular-level structural analysis quantitatively demonstrated the synegtestic interplay of ingredients to achieve a high antibacterial activity.

SUBMITTER: Thoma J

PROVIDER: S-EPMC7378190 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Specific localisation of ions in bacterial membranes unravels physical mechanism of effective bacteria killing by sanitiser.

Thoma Judith J Abuillan Wasim W Furikado Ippei I Habe Taichi T Yamamoto Akihisa A Gierlich Simone S Kaufmann Stefan S Brandenburg Klaus K Gutsmann Thomas T Konovalov Oleg O Inoue Shigeto S Tanaka Motomu M

Scientific reports 20200723 1

Antimicrobial resistance is a major threat to public health. Although many commercial sanitisers contain a combination of cationic surfactants and aromatic alcohols, the physical mechanisms where these two substances bind to or how they disturb bacterial membranes are still largely unknown. In this study, we designed a well-defined model of Gram-negative bacteria surfaces based on the monolayer of lipopolysaccharides with uniform saccharide head groups. Since commonly used X-ray reflectivity is ...[more]

PMID: 32704045

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Project description:Serious infection caused by multi-drug-resistant bacteria is a major threat to human health. Bacteria can invade the host tissue and produce various toxins to damage or kill host cells, which may induce life-threatening sepsis. Here, we aimed to explore whether fructose-coated Ångstrom-scale silver particles (F-AgÅPs), which were prepared by our self-developed evaporation-condensation system and optimized coating approach, could kill bacteria and sequester bacterial toxins to attenuate fatal bacterial infections. Methods: A series of in vitro assays were conducted to test the anti-bacterial efficacy of F-AgÅPs, and to investigate whether F-AgÅPs could protect against multi-drug resistant Staphylococcus aureus (S. aureus)- and Escherichia coli (E. coli)-induced cell death, and suppress their toxins (S. aureus hemolysin and E. coli lipopolysaccharide)-induced cell injury or inflammation. The mouse models of cecal ligation and puncture (CLP)- or E. coli bloodstream infection-induced lethal sepsis were established to assess whether the intravenous administration of F-AgÅPs could decrease bacterial burden, inhibit inflammation, and improve the survival rates of mice. The levels of silver in urine and feces of mice were examined to evaluate the excretion of F-AgÅPs. Results: F-AgÅPs efficiently killed various bacteria that can cause lethal infections and also competed with host cells to bind with S. aureus α-hemolysin, thus blocking its cytotoxic activity. F-AgÅPs inhibited E. coli lipopolysaccharide-induced endothelial injury and macrophage inflammation, but not by directly binding to lipopolysaccharide. F-AgÅPs potently reduced bacterial burden, reversed dysregulated inflammation, and enhanced survival in mice with CLP- or E. coli bloodstream infection-induced sepsis, either alone or combined with antibiotic therapy. After three times injections within 48 h, 79.18% of F-AgÅPs were excreted via feces at the end of the 14-day observation period. Conclusion: This study suggests the prospect of F-AgÅPs as a promising intravenous agent for treating severe bacterial infections.

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Specific localisation of ions in bacterial membranes unravels physical mechanism of effective bacteria killing by sanitiser.

Publications

Specific localisation of ions in bacterial membranes unravels physical mechanism of effective bacteria killing by sanitiser.

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