- ANTIBIOTIC COMPOUNDS
-
The present application provides compounds and methods for treating bacterial infections, including bacterial infections caused by MRSA.
- -
-
Page/Page column 58; 59
(2020/12/30)
-
- A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus
-
Treatment of Staphylococcus aureus infections is complicated by the development of antibiotic tolerance, a consequence of the ability of S. aureus to enter into a nongrowing, dormant state in which the organisms are referred to as persisters. We report that the clinically approved anthelmintic agent bithionol kills methicillinresistant S. aureus (MRSA) persister cells, which correlates with its ability to disrupt the integrity of Gram-positive bacterial membranes. Critically, bithionol exhibits significant selectivity for bacterial compared with mammalian cell membranes. All-atom molecular dynamics (MD) simulations demonstrate that the selectivity of bithionol for bacterial membranes correlates with its ability to penetrate and embed in bacterial-mimic lipid bilayers, but not in cholesterol-rich mammalian-mimic lipid bilayers. In addition to causing rapid membrane permeabilization, the insertion of bithionol increases membrane fluidity. By using bithionol and nTZDpa (another membraneactive antimicrobial agent), as well as analogs of these compounds, we show that the activity of membrane-active compounds against MRSA persisters positively correlates with their ability to increase membrane fluidity, thereby establishing an accurate biophysical indicator for estimating antipersister potency. Finally, we demonstrate that, in combination with gentamicin, bithionol effectively reduces bacterial burdens in a mouse model of chronic deep-seated MRSA infection. This work highlights the potential repurposing of bithionol as an antipersister therapeutic agent.
- Kim, Wooseong,Zou, Guijin,Hari, Taylor P. A.,Wilt, Ingrid K.,Zhu, Wenpeng,Galle, Nicolas,Faizi, Hammad A.,Hendricks, Gabriel L.,Tori, Katerina,Pan, Wen,Huang, Xiaowen,Steele, Andrew D.,Csatary, Erika E.,Dekarske, Madeline M.,Rosen, Jake L.,De Queiroz Ribeiro, Noelly,Lee, Kiho,Port, Jenna,Fuchs, Beth Burgwyn,Vlahovska, Petia M.,Wuest, William M.,Gao, Huajian,Ausubel, Frederick M.,Mylonakis, Eleftherios
-
p. 16529 - 16534
(2019/08/20)
-
- Compositions
-
The problem of providing a storage stable anti-calculus toothpaste comprising a tripolyphosphate salt is remedied by incorporating more than 4% of the salt and having the pH from about 8 to about 10. A tripolyphosphate salt may also be combined with a noncationic anti-bacterial agent such as triclosan to provide a composition having anti-calculus and anti-plaque activity.
- -
-
-
- Carbonates of acetylenic alcohols
-
Polymerizable carbonate compounds of the formula: wherein A is an aromatic polycycle, R1 and R2 are independently hydrogen atom or alkyl, and n is 1, 2 or 3, are disclosed. They are useful as a component of nonemanating, self-curing and heat resistant resin compositions.
- -
-
-
- Dentifrice compositions
-
It is disclosed that a dentifrice which includes a surfactant and an anti-plaque agent comprising a substantially water-insoluble non-cationic antimicrobial agent or a zinc salt or a mixture thereof has enhanced activity when the dentifrice comprises at least 0.2% by weight of a lamellar liquid crystal surfactant phase having a lamellar spacing of less than 6.0 nm.
- -
-
-
- Anticalculus composition
-
This invention relates to an improved composition for inhibiting dental plaque and calculus formation, comprising zinc ions and a non-toxic, organoleptically acceptable antibacterial agent in an orally acceptable medium, and to a process for retarding the growth of dental plaque and calculus by application to the teeth of the above composition.
- -
-
-
