کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5667120 1591745 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium
چکیده انگلیسی


- Compound 1771 is a small-molecule inhibitor of LtaS synthase.
- Compound 1771 inhibits lipoteichoic acid (LTA) synthesis at the surface of Enterococcus faecium.
- LTA synthesis inhibition in E. faecium led to a growth reduction and loss of cell aggregation.
- LTA synthesis inhibition by 1771 in combination with antibiotics did not affect 16 biofilms.
- LTA synthesis inhibition by 1771 in combination with either gentamicin or daptomycin abrogates growth.

Enterococcus faecium is a multidrug-resistant (MDR) nosocomial pathogen causing significant morbidity in debilitated patients. New antimicrobials are needed to treat antibiotic-resistant E. faecium infections in hospitalised patients. E. faecium incorporates lipoteichoic acid (LTA) (1,3-polyglycerol-phosphate linked to glycolipid) in its cell wall. The small-molecule inhibitor 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] specifically blocks the activity of Staphylococcus aureus LtaS synthase, which polymerises 1,3-glycerolphosphate into LTA polymers. Here we characterised the effects of the small-molecule inhibitor 1771 on the growth of E. faecium isolates, alone (28 strains) or in combination with the antibiotics vancomycin, daptomycin, ampicillin, gentamicin or linezolid (15 strains), and on biofilm formation (16 strains). Inhibition of LTA synthesis at the surface of the cell by compound 1771 in combination with current antibiotic therapy abrogates enterococcal growth in vitro but does not affect mature E. faecium biofilms. Targeting LTA synthesis may provide new possibilities to treat MDR E. faecium infections.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 49, Issue 3, March 2017, Pages 355-363
نویسندگان
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