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……中致病性和毒力的表型及遗传预测因子

Phenotypic and Genetic Predictors of Pathogenicity and Virulence in .

作者信息

Sundell Krister, Landor Lotta, Nicolas Pierre, Jørgensen Jóhanna, Castillo Daniel, Middelboe Mathias, Dalsgaard Inger, Donati Valentina Laura, Madsen Lone, Wiklund Tom

机构信息

Laboratory of Aquatic Pathobiology, Environmental and Marine Biology, Åbo Akademi University, Turku, Finland.

Unité Mathématiques et Informatique Appliquées du Génome à l'Environnement (MaIAGE), Institut National de la Recherche Agronomique, Université Paris-Saclay, Jouy-en-Josas, France.

出版信息

Front Microbiol. 2019 Jul 24;10:1711. doi: 10.3389/fmicb.2019.01711. eCollection 2019.

Abstract

causes bacterial cold-water disease (BCWD) in farmed rainbow trout (), with the multilocus sequence typing (MLST) clonal complex (CC) CC-ST10 accounting for the majority of outbreaks globally. The development of alternative strategies to antibiotic treatment of BCWD using bacteriophage-based control of , or virulence factors as targets for therapy, requires knowledge of the phage-sensitivity of outbreak strains and of universal traits contributing to their pathogenicity. To examine the association between virulence and both genetic (MLST sequence type (ST) and PCR-serotype) and phenotypic characteristics (adherence, antibiotic resistance, colony spreading motility, hemolytic and proteolytic activity), the median lethal dose (LD) of 26 geographically disparate isolates was determined in rainbow trout. Furthermore, the sensitivity of the isolates against five bacteriophages was determined by the efficiency of plating (EOP). The tested isolates were mainly represented by CC-ST10 genotypes (22 out of 26) and showed up to 3-log differences in LD (8.9 × 10 to 3.1 × 10 CFU). No association between MLST ST and virulence was found because of a high variation in LD within STs. All identified serotypes (0, 1, and 2) were pathogenic, but ten most virulent isolates belonged to serotype 1 or 2. Isolates of high (LD < 10 CFU), moderate (LD = 10-10 CFU), and weak (LD > 10 CFU) virulence were similar in phenotypic characteristics . However, the only non-virulent CC-ST10 isolate was deficient in spreading motility and proteolytic activity, indicating that the characteristics are required for pathogenicity in . Univariate correlation studies found only non-significant associations between LD and the measured phenotypic characteristics, and the multivariable analysis did neither reveal any significant predictors of virulence. The majority of isolates (16 out of 26) were sensitive to at least four bacteriophages, with up to a 6-log variation in the EOP. Most CC-ST10 isolates (16 out of 22) were sensitive to the examined phages, including 5 out of the 7 most virulent isolates represented by prevalent and antibiotic-resistant STs. Our findings suggest that control of BCWD using lytic phages or interventions targeting shared characteristics of pathogenic strains should be further explored.

摘要

在养殖虹鳟鱼中引发细菌性冷水病(BCWD),多位点序列分型(MLST)克隆复合体(CC)CC - ST10在全球大多数疫情爆发中占主导。开发基于噬菌体控制或针对毒力因子作为治疗靶点的BCWD抗生素替代治疗策略,需要了解疫情爆发菌株的噬菌体敏感性以及导致其致病性的普遍特征。为了研究毒力与遗传特征(MLST序列类型(ST)和PCR血清型)以及表型特征(黏附、抗生素抗性、菌落扩散运动性、溶血和蛋白水解活性)之间的关联,测定了26株来自不同地理区域的菌株在虹鳟鱼中的半数致死剂量(LD)。此外,通过平板效率(EOP)测定了这些菌株对五种噬菌体的敏感性。所测试的菌株主要以CC - ST10基因型为主(26株中有22株),LD显示出高达3个对数级的差异(8.9×10至3.1×10 CFU)。由于各ST内LD变化较大,未发现MLST ST与毒力之间存在关联。所有鉴定出的血清型(0、1和2)均具有致病性,但10株最具毒力的菌株属于血清型1或2。高毒力(LD < 10 CFU)、中毒力(LD = 10 - 10 CFU)和低毒力(LD > 10 CFU)的菌株在表型特征上相似。然而,唯一无毒力的CC - ST10菌株在扩散运动性和蛋白水解活性方面存在缺陷,表明这些特征是该菌致病性所必需的。单变量相关性研究仅发现LD与所测表型特征之间存在不显著的关联,多变量分析也未揭示任何毒力的显著预测因子。大多数菌株(26株中有16株)对至少四种噬菌体敏感,EOP变化高达6个对数级。大多数CC - ST10菌株(22株中有16株)对所检测的噬菌体敏感,包括7株最具毒力的菌株中由流行和抗生素抗性ST代表的5株。我们的研究结果表明,应进一步探索使用裂解性噬菌体控制BCWD或针对致病菌株共同特征进行干预的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07a5/6668605/a5ad9e11d2a4/fmicb-10-01711-g001.jpg

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