Department of Clinical Sciences Lund, Division of Infection Medicine, Lund University, Lund, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Microbiol Spectr. 2023 Aug 17;11(4):e0019523. doi: 10.1128/spectrum.00195-23. Epub 2023 Jun 7.
is a genus of Gram-negative rods, which can cause persistent airway infections in people with cystic fibrosis (CF). The knowledge about virulence and clinical implications of is still limited, and it is not fully established whether infections contribute to disease progression or if it is a marker of poor lung function. The most commonly reported species in CF is A. xylosoxidans. While other spp. are also identified in CF airways, the currently used Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometry (MALDI-TOF MS) method in routine diagnostics cannot distinguish between species. Differences in virulence between species have consequently not been well studied. In this study, we compare phenotypes and proinflammatory properties of A. xylosoxidans, , , and using models. Bacterial supernatants were used to stimulate CF bronchial epithelial cells and whole blood from healthy individuals. Supernatants from the well-characterized CF-pathogen Pseudomonas aeruginosa were included for comparison. Inflammatory mediators were analyzed with ELISA and leukocyte activation was assessed using flow cytometry. The four species differed in morphology seen in scanning electron microscopy (SEM), but there were no observed differences in swimming motility or biofilm formation. Exoproducts from all species except caused significant IL-6 and IL-8 secretion from CF lung epithelium. The cytokine release was equivalent or stronger than the response induced by P. aeruginosa. All species activated neutrophils and monocytes in a lipopolysaccharide (LPS)-independent manner. Our results indicate that exoproducts of the four included species do not differ consistently in causing inflammatory responses, but they are equally or even more capable of inducing inflammation compared with the classical CF pathogen P. aeruginosa. Achromobacter xylosoxidans is an emerging pathogen among people with cystic fibrosis (CF). Current routine diagnostic methods are often unable to distinguish A. xylosoxidans from other species, and the clinical relevance of different species is still unknown. In this work, we show that four different species relevant to CF evoke similar inflammatory responses from airway epithelium and leukocytes , but they are all equally or even more proinflammatory compared to the classic CF-pathogen Pseudomonas aeruginosa. The results suggest that species are important airway pathogens in CF, and that all species are relevant to treat.
是一组革兰氏阴性杆菌，可引起囊性纤维化 (CF) 患者持续的气道感染。目前关于该菌的毒力和临床意义的知识仍然有限，尚不完全确定感染是否会导致疾病进展，或者它是否是肺功能不佳的标志物。CF 中最常报道的 是 A. xylosoxidans。虽然在 CF 气道中也鉴定出其他 spp.，但目前常规诊断中使用的基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF MS) 方法无法区分物种。因此，不同物种之间的毒力差异尚未得到很好的研究。在这项研究中，我们使用 CF 气道模型比较了 A. xylosoxidans、、、和 的表型和促炎特性。使用细菌上清液刺激 CF 支气管上皮细胞和健康个体的全血。还包括了经过充分表征的 CF 病原体铜绿假单胞菌的上清液进行比较。使用 ELISA 分析炎症介质，使用流式细胞术评估白细胞激活。在扫描电子显微镜 (SEM) 中观察到的四种 形态不同，但游动性或生物膜形成没有观察到差异。除 外，所有 物种的外产物均导致 CF 肺上皮细胞中 IL-6 和 IL-8 的分泌显著增加。细胞因子释放与铜绿假单胞菌诱导的反应相当或更强。所有 物种均以 LPS 非依赖性方式激活中性粒细胞和单核细胞。我们的结果表明，四种包括的 物种的外产物在引起炎症反应方面没有一致的差异，但与经典 CF 病原体铜绿假单胞菌相比，它们同样能够甚至更能诱导炎症。木糖氧化无色杆菌是囊性纤维化 (CF) 人群中的一种新兴病原体。目前的常规诊断方法通常无法将木糖氧化无色杆菌与其他 物种区分开来，不同物种的临床相关性仍不清楚。在这项工作中，我们表明，与 CF 相关的四种不同的 物种均能从气道上皮细胞和白细胞中引起类似的炎症反应，与经典 CF 病原体铜绿假单胞菌相比，它们同样能够甚至更能诱导炎症。结果表明， 物种是 CF 中的重要气道病原体，所有 物种都与治疗相关。
