Sager Martin, Benten W Peter M, Engelhardt Eva, Gougoula Christina, Benga Laurentiu
Central Animal Research Facility, Heinrich-Heine-University, University Hospital, Düsseldorf, Germany.
PLoS One. 2015 Oct 2;10(10):e0138778. doi: 10.1371/journal.pone.0138778. eCollection 2015.
[Pasteurella] pneumotropica biotypes Jawetz and Heyl and [Actinobacillus] muris are the most prevalent Pasteurellaceae species isolated from laboratory mouse. However, mechanisms contributing to their high prevalence such as the ability to form biofilms have not been studied yet. In the present investigation we analyze if these bacterial species can produce biofilms in vitro and investigate whether proteins, extracellular DNA and polysaccharides are involved in the biofilm formation and structure by inhibition and dispersal assays using proteinase K, DNase I and sodium periodate. Finally, the capacity of the biofilms to confer resistance to antibiotics is examined. We demonstrate that both [P.] pneumotropica biotypes but not [A.] muris are able to form robust biofilms in vitro, a phenotype which is widely spread among the field isolates. The biofilm inhibition and dispersal assays by proteinase and DNase lead to a strong inhibition in biofilm formation when added at the initiation of the biofilm formation and dispersed pre-formed [P.] pneumotropica biofilms, revealing thus that proteins and extracellular DNA are essential in biofilm formation and structure. Sodium periodate inhibited the bacterial growth when added at the beginning of the biofilm formation assay, making difficult the assessment of the role of β-1,6-linked polysaccharides in the biofilm formation, and had a biofilm stimulating effect when added on pre-established mature biofilms of [P.] pneumotropica biotype Heyl and a majority of [P.] pneumotropica biotype Jawetz strains, suggesting that the presence of β-1,6-linked polysaccharides on the bacterial surface might attenuate the biofilm production. Conversely, no effect or a decrease in the biofilm quantity was observed by biofilm dispersal using sodium periodate on further biotype Jawetz isolates, suggesting that polysaccharides might be incorporated in the biofilm structure. We additionally show that [P.] pneumotropica cells enclosed in biofilms were less sensitive to treatment with amoxicillin and enrofloxacin than planktonic bacteria. Taken together, these findings provide a first step in understanding of the biofilm mechanisms in [P.] pneumotropica, which might contribute to elucidation of colonization and pathogenesis mechanisms for these obligate inhabitants of the mouse mucosa.
嗜肺巴斯德菌生物型Jawetz和Heyl以及鼠放线杆菌是从实验小鼠中分离出的最常见的巴斯德菌科物种。然而,导致它们高流行率的机制,如形成生物膜的能力,尚未得到研究。在本研究中,我们分析了这些细菌物种是否能在体外产生生物膜,并通过使用蛋白酶K、脱氧核糖核酸酶I和高碘酸钠的抑制和分散试验,研究蛋白质、细胞外DNA和多糖是否参与生物膜的形成和结构。最后,检测了生物膜赋予抗生素抗性的能力。我们证明,两种嗜肺巴斯德菌生物型都能在体外形成坚固的生物膜,而鼠放线杆菌则不能,这种表型在野外分离株中广泛存在。蛋白酶和脱氧核糖核酸酶的生物膜抑制和分散试验表明,在生物膜形成开始时添加会导致生物膜形成受到强烈抑制,并且能分散预先形成的嗜肺巴斯德菌生物膜,从而揭示蛋白质和细胞外DNA在生物膜形成和结构中至关重要。在生物膜形成试验开始时添加高碘酸钠会抑制细菌生长,这使得评估β-1,6-连接多糖在生物膜形成中的作用变得困难,而在预先建立的嗜肺巴斯德菌生物型Heyl和大多数嗜肺巴斯德菌生物型Jawetz菌株的成熟生物膜上添加时,具有生物膜刺激作用,这表明细菌表面β-1,6-连接多糖的存在可能会减弱生物膜的产生。相反,用高碘酸钠对其他生物型Jawetz分离株进行生物膜分散时,未观察到生物膜量有影响或减少,这表明多糖可能被纳入生物膜结构中。我们还表明,包裹在生物膜中的嗜肺巴斯德菌细胞比浮游细菌对阿莫西林和恩诺沙星治疗的敏感性更低。综上所述,这些发现为理解嗜肺巴斯德菌的生物膜机制提供了第一步,这可能有助于阐明这些小鼠黏膜专性定殖菌的定殖和致病机制。