Gracia E, Fernández A, Conchello P, Alabart J L, Pérez M, Amorena B
CSIC-SIA, Department of Animal Health, Aptdo. 727, 50080 Zaragoza, Spain.
Luminescence. 1999 Jan-Feb;14(1):23-31. doi: 10.1002/(SICI)1522-7243(199901/02)14:1<23::AID-BIO513>3.0.CO;2-M.
In this work, a method was developed to establish Staphylococcus aureus biofilms on 96-well plates and automatically quantify viable cells within these biofilms by ATP-bioluminescence. Different strains were compared for biofilm formation. Cells from slime producing (SP) strain variants were more adherent (p < 0.001) and therefore more suitable for biofilm formation than non-slime producing original isolates. To compare biofilm support surfaces, SP biofilms were formed for 6, 24 and 48 h on 96-well polystyrene plates, containing wells coated with gelatin, poly-L-lysine or pre-treated for tissue culture and uncoated wells. Tissue culture-treated wells enhanced biofilm formation, allowing the highest growth (p < 0.001) in well-established biofilms (24 or 48 h old). For ATP quantification, the efficacy of different ATP extractants was compared: dimethyl sulphoxide (DMSO), trichloroacetic acid (TCA), a commercially available releasing reagent(R) (RR) and lysostaphin. A greater inhibitory effect on the ATP detection (p < 0.01), a more variable light emission (variation coefficient >/=50% vs. <19%, respectively) and a lower extraction efficiency (p < 0.05) were found in the case of TCA or lysostaphin in relation to RR or DMSO. DMSO was found preferable in relation to RR (upper detection limits 2.3 x 10(9) and 2 x 10(8) CFU/mL respectively) for bacterial ATP extraction from biofilms with high bacterial density. DMSO extracted ATP within seconds, light emission being stable for 6 h. The method developed allows automated viability determination of biofilm cells using bioluminescence and simultaneous study of factors affecting this viability (culture media, antibiotic types, antimicrobial concentrations, support surfaces and biofilm ages). It may be of use in bacteriological and antimicrobial research.
在本研究中,开发了一种在96孔板上建立金黄色葡萄球菌生物膜并通过ATP生物发光自动定量这些生物膜内活细胞的方法。比较了不同菌株的生物膜形成情况。与不产生黏液的原始分离株相比,产生黏液(SP)的菌株变体的细胞更具黏附性(p < 0.001),因此更适合形成生物膜。为了比较生物膜支持表面,在96孔聚苯乙烯板上形成SP生物膜6、24和48小时,这些孔板包含涂有明胶、聚-L-赖氨酸的孔或经过组织培养预处理的孔以及未涂覆的孔。经过组织培养处理的孔增强了生物膜的形成,在成熟生物膜(24或48小时龄)中实现了最高生长(p < 0.001)。对于ATP定量,比较了不同ATP提取剂的效果:二甲基亚砜(DMSO)、三氯乙酸(TCA)、市售释放试剂(R)(RR)和溶葡萄球菌素。与RR或DMSO相比,TCA或溶葡萄球菌素对ATP检测具有更大的抑制作用(p < 0.01)、更可变的发光(变异系数分别> /= 50%对< 19%)和更低的提取效率(p < 0.05)。对于从高细菌密度生物膜中提取细菌ATP,发现DMSO相对于RR更可取(上检测限分别为2.3 x 10(9)和2 x 10(8) CFU/mL)。DMSO在数秒内即可提取ATP,发光在6小时内保持稳定。所开发的方法允许使用生物发光自动测定生物膜细胞的活力,并同时研究影响这种活力的因素(培养基、抗生素类型、抗菌浓度、支持表面和生物膜年龄)。它可能在细菌学和抗菌研究中有用。