PDF(Pubmed)
Abstract：
The rapid emergence of invasive infections caused by azole-resistant Candida tropicalis has become a public health concern, and there is an urgent need for alternative treatment strategies. Studies have demonstrated the antibacterial effects of nisin, a well-known peptide naturally produced by Lactococcus lactis subsp. lactis. However, there is scant information about the antifungal effect of nisin against C. tropicalis. The present study aims to investigate the in vitro antifungal activity of nisin against clinical isolates of azole-resistant C. tropicalis strains, as well as its inhibitory effect on biofilm formation. A total of 35 C. tropicalis strains isolated from patients with invasive fungal infections were divided into the azole-resistant group and the azole-sensitive group, containing 21 and 14 strains, respectively. The relative expression levels of the ERG11 and UPC2 genes in the azole-resistant group were higher than those in the azole-sensitive group (p < 0.0001), while no significant differences were observed in the expression levels of the MDR1 and CDR1 genes. The minimum inhibitory concentration of nisin against C. tropicalis ranged from 2 to 8 μg/mL. Nisin treatment inhibited the growth of azole-resistant C. tropicalis, with over a four-fold reduction in OD600 nm values observed at the 8-h time point, while it promoted the transition of C. tropicalis from the spore phase to the hyphal phase, as observed on cryo-scanning electron microscopy. The results of biofilm quantification using crystal violet staining indicated a significant decrease in OD570 nm values in the nisin-treated group compared to the controls (p < 0.0001). Among the 21 azole-resistant C. tropicalis strains, the biofilm formation was inhibited in 17 strains (17/21, 81%), and more than 85% inhibition of biofilm formation was observed in the representative strains. With regard to the molecular mechanisms, the expression of the BCR1 and UPC2 genes in the azole-resistant strains was down-regulated on nisin treatment (p < 0.05). In conclusion, we demonstrated, for the first time, that nisin has antifungal activity and significant anti-biofilm activity against clinical isolates of azole-resistant C. tropicalis strains. Based on the findings, nisin could be a promising alternative antifungal agent for combating azole-resistant C. tropicalis infections.
摘要：
由耐唑的热带念珠菌引起的侵袭性感染的迅速出现已成为公共卫生关注的问题,迫切需要替代治疗策略。研究证明了乳酸链球菌素的抗菌作用，乳酸乳球菌亚种天然产生的一种众所周知的肽。乳酸。然而,关于乳酸链球菌素对热带梭菌的抗真菌作用的信息很少。本研究旨在研究乳酸链球菌素对临床分离的耐唑类耐药热带假丝酵母菌的体外抗真菌活性,以及它对生物膜形成的抑制作用。将从侵袭性真菌感染患者中分离的35株热带梭菌分为唑类耐药组和唑类敏感组,含21株和14株，分别。ERG11和UPC2基因在唑类耐药组中的相对表达水平高于唑类敏感组(p<0.0001),而MDR1和CDR1基因的表达水平没有显着差异。乳链菌肽对热带梭菌的最小抑制浓度为2至8μg/mL。Nisin处理抑制了对唑类耐药的热带念珠菌的生长，在8小时的时间点观察到的OD600nm值减少了4倍以上，虽然它促进了热带念珠菌从孢子相向菌丝相的转变，在低温扫描电子显微镜上观察到。使用结晶紫染色的生物膜定量结果表明,与对照相比,乳链菌肽处理组中的OD570nm值显著降低(p<0.0001)。在21株对唑类耐药的热带念珠菌中，生物膜形成受到抑制的菌株有17株(17/21,81%),在代表性菌株中观察到超过85%的生物膜形成抑制。关于分子机制，Nisin处理后，唑类耐药菌株中BCR1和UPC2基因的表达下调（p<0.05）。总之,我们展示了，第一次,表明乳酸链球菌素具有抗真菌活性和显著的抗生物膜活性。根据调查结果,乳链菌肽可能是一种有前途的替代抗真菌剂，用于对抗耐药的热带梭菌感染。
