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来自游走性红斑患者的生物膜形成细菌的基因组特征及抗生素敏感性

Genomic characterization and antibiotic susceptibility of biofilm-forming and from patients with erythema migrans.

作者信息

Fabrizio Giorgia, Cavallo Ilaria, Sivori Francesca, Truglio Mauro, Kovacs Daniela, Francalancia Massimo, D'Agosto Giovanna, Trento Elisabetta, Prignano Grazia, Mastrofrancesco Arianna, Ruzič-Sabljič Eva, Pimpinelli Fulvia, Di Domenico Enea Gino

机构信息

1Department of Biology and Biotechnology "C. Darwin" Sapienza University of Rome, Rome, Italy.

Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

出版信息

Front Cell Infect Microbiol. 2025 Jul 7;15:1619660. doi: 10.3389/fcimb.2025.1619660. eCollection 2025.

DOI:10.3389/fcimb.2025.1619660
PMID:40692686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12277364/
Abstract

BACKGROUND

and are the leading causes of Lyme borreliosis (LB) in Europe. Persistent LB forms may involve biofilms, potentially contributing to antibiotic tolerance.

METHODS

Whole genome sequencing (WGS) was conducted on 7 and 5 isolates from erythema migrans skin biopsies. Biofilms were analyzed for extracellular DNA (eDNA) content and biomass. A phenol red metabolic assay assessed the minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) of amoxicillin, azithromycin, ceftriaxone, and doxycycline.

RESULTS

Phylogenetic analysis revealed and formed distinct clades, while B31 clustered separately. Core genome analysis showed 38.9% of genes were shared between and , decreasing to 26.1% with . The cloud genome expanded from 34.4% to 53.4% with the addition of . No antimicrobial resistance genes were detected. Surface adhesion gene profiles exhibited significant variation across species, suggesting potential functional differences in host adaptation. and species exhibited biofilms, with biomass correlating significantly with eDNA production. MIC values were 0.25 μg/mL (amoxicillin, ceftriaxone), 0.125 μg/mL (azithromycin), and 0.5 μg/mL (doxycycline), with no significant interspecies differences. However, MBIC values were considerably higher: 2 μg/mL (amoxicillin, azithromycin), 16 μg/mL (ceftriaxone), and 32 μg/mL (doxycycline).

CONCLUSIONS

Biofilms in and significantly reduce antibiotic efficacy, particularly ceftriaxone and doxycycline. These findings highlight the need for targeted therapeutic strategies and suggest biofilms may impact treatment outcomes in LB.

摘要

背景

伯氏疏螺旋体和伽氏疏螺旋体是欧洲莱姆病(LB)的主要病因。持续性莱姆病形式可能涉及生物膜,这可能导致抗生素耐受性。

方法

对来自游走性红斑皮肤活检的7株伯氏疏螺旋体和5株伽氏疏螺旋体分离株进行全基因组测序。分析生物膜的细胞外DNA(eDNA)含量和生物量。采用酚红代谢试验评估阿莫西林、阿奇霉素、头孢曲松和多西环素的最低抑菌浓度(MIC)和最低生物膜抑菌浓度(MBIC)。

结果

系统发育分析显示,伯氏疏螺旋体和伽氏疏螺旋体形成不同的进化枝,而狭义伯氏疏螺旋体B31单独聚类。核心基因组分析表明,伯氏疏螺旋体和伽氏疏螺旋体之间有38.9%的基因相同,与狭义伯氏疏螺旋体B31相比则降至26.1%。随着伽氏疏螺旋体的加入,云基因组从34.4%扩展到53.4%。未检测到抗菌抗性基因。表面粘附基因谱在不同物种间表现出显著差异,表明在宿主适应性方面可能存在潜在的功能差异。伯氏疏螺旋体和伽氏疏螺旋体物种表现出生物膜,生物量与eDNA产生显著相关。MIC值分别为0.25μg/mL(阿莫西林、头孢曲松)、0.125μg/mL(阿奇霉素)和0.5μg/mL(多西环素),物种间无显著差异。然而,MBIC值要高得多:2μg/mL(阿莫西林、阿奇霉素)、16μg/mL(头孢曲松)和32μg/mL(多西环素)。

结论

伯氏疏螺旋体和伽氏疏螺旋体中的生物膜显著降低抗生素疗效,尤其是头孢曲松和多西环素。这些发现突出了针对性治疗策略的必要性,并表明生物膜可能影响莱姆病的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/846894cb018c/fcimb-15-1619660-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/15065b1b6f90/fcimb-15-1619660-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/8a173dc1b4a7/fcimb-15-1619660-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/846894cb018c/fcimb-15-1619660-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/15065b1b6f90/fcimb-15-1619660-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/8a173dc1b4a7/fcimb-15-1619660-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ca/12277364/846894cb018c/fcimb-15-1619660-g003.jpg

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