Musafer Hadeel K, Kuchma Sherry L, Naimie Amanda A, Schwartzman Joseph D, Al-Mathkhury Harith J Fahad, O'Toole George A
Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq.
Microb Ecol. 2014 Jul;68(1):111-20. doi: 10.1007/s00248-013-0361-6. Epub 2014 Jan 17.
Pseudomonas aeruginosa, a ubiquitous environmental organism, is a difficult-to-treat opportunistic pathogen due to its broad-spectrum antibiotic resistance and its ability to form biofilms. In this study, we investigate the link between resistance to a clinically important antibiotic, imipenem, and biofilm formation. First, we observed that the laboratory strain P. aeruginosa PAO1 carrying a mutation in the oprD gene, which confers resistance to imipenem, showed a modest reduction in biofilm formation. We also observed an inverse relationship between imipenem resistance and biofilm formation for imipenem-resistant strains selected in vitro, as well as for clinical isolates. We identified two clinical isolates of P. aeruginosa from the sputum of cystic fibrosis patients that formed robust biofilms, but were sensitive to imipenem (MIC ≤ 2 μg/ml). To test the hypothesis that there is a general link between imipenem resistance and biofilm formation, we performed transposon mutagenesis of these two clinical strains to identify mutants defective in biofilm formation, and then tested these mutants for imipenem resistance. Analysis of the transposon mutants revealed a role for previously described biofilm factors in these clinical isolates of P. aeruginosa, including mutations in the pilY1, pilX, pilW, algC, and pslI genes, but none of the biofilm-deficient mutants became imipenem resistant (MIC ≥ 8 μg/ml), arguing against a general link between biofilm formation and resistance to imipenem. Thus, assessing biofilm formation capabilities of environmental isolates is unlikely to serve as a good predictor of imipenem resistance. We also discuss our findings in light of the limited literature addressing planktonic antibiotic resistance factors that impact biofilm formation.
铜绿假单胞菌是一种广泛存在于环境中的微生物，由于其具有广谱抗生素耐药性以及形成生物膜的能力，是一种难以治疗的机会致病菌。在本研究中，我们调查了对临床上重要的抗生素亚胺培南的耐药性与生物膜形成之间的联系。首先，我们观察到携带oprD基因突变（该突变赋予对亚胺培南的耐药性）的实验室菌株铜绿假单胞菌PAO1，其生物膜形成略有减少。我们还观察到，对于体外筛选出的亚胺培南耐药菌株以及临床分离株，亚胺培南耐药性与生物膜形成之间存在负相关关系。我们从囊性纤维化患者的痰液中鉴定出两株铜绿假单胞菌临床分离株，它们能形成强大的生物膜，但对亚胺培南敏感（最低抑菌浓度≤2μg/ml）。为了验证亚胺培南耐药性与生物膜形成之间存在普遍联系这一假设，我们对这两株临床菌株进行转座子诱变，以鉴定生物膜形成缺陷的突变体，然后测试这些突变体对亚胺培南的耐药性。对转座子突变体的分析揭示了先前描述的生物膜因子在这些铜绿假单胞菌临床分离株中的作用，包括pilY1、pilX、pilW、algC和pslI基因中的突变，但没有一个生物膜缺陷突变体对亚胺培南产生耐药性（最低抑菌浓度≥8μg/ml），这表明生物膜形成与对亚胺培南的耐药性之间不存在普遍联系。因此，评估环境分离株的生物膜形成能力不太可能作为亚胺培南耐药性的良好预测指标。我们还结合关于影响生物膜形成的浮游抗生素耐药因子的有限文献讨论了我们的研究结果。
