Evaluation of anti-biofilm activity of acidic amino acids and synergy with ciprofloxacin on Staphylococcus aureus biofilms

被引:65
|
作者
Warraich, Annsar A. [1 ,4 ]
Mohammed, Afzal R. [1 ]
Perrie, Yvonne [2 ]
Hussain, Majad [3 ]
Gibson, Hazel [4 ]
Rahman, Ayesha [4 ]
机构
[1] Aston Univ, Aston Pharm Sch, Birmingham B4 7ET, W Midlands, England
[2] Univ Strathclyde, Glasgow G1 1XQ, Lanark, Scotland
[3] Quest Healthcare Ltd, Birmingham, W Midlands, England
[4] Univ Wolverhampton, Wolverhampton WV1 1LY, England
基金
英国生物技术与生命科学研究理事会;
关键词
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; EXTRACELLULAR DNA; STREPTOCOCCUS-PNEUMONIAE; BACILLUS-SUBTILIS; ALPHA-ENOLASE; PROTEIN; SURFACE; RESISTANCE; RELEASE; MODEL;
D O I
10.1038/s41598-020-66082-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Acidic amino acids, aspartic acid (Asp) and glutamic acid (Glu) can enhance the solubility of many poorly soluble drugs including ciprofloxacin (Cip). One of the mechanisms of resistance within a biofilm is retardation of drug diffusion due to poor penetration across the matrix. To overcome this challenge, this work set to investigate novel counter ion approach with acidic amino acids, which we hypothesised will disrupt the biofilm matrix as well as simultaneously improve drug effectiveness. The anti-biofilm activity of D-Asp and D-Glu was studied on Staphylococcus aureus biofilms. Synergistic effect of combining D-amino acids with Cip was also investigated as a strategy to overcome anti-microbial resistance in these biofilms. Interestingly at equimolar combinations, D-Asp and D-Glu were able to significantly disperse (at 20mM and 40mM) established biofilms and inhibit (at 10mM, 20mM and 40mM) new biofilm formation in the absence of an antibiotic. Moreover, our study confirmed L-amino acids also exhibit anti-biofilm activity. The synergistic effect of acidic amino acids with Cip was observed at lower concentration ranges (<40mM amino acids and <90.54 mu M, respectively), which resulted in 96.89% (inhibition) and 97.60% (dispersal) reduction in CFU with exposure to 40mM amino acids. Confocal imaging indicated that the amino acids disrupt the honeycomb-like extracellular DNA (eDNA) meshwork whilst also preventing its formation.
引用
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页数:14
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