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解读糖尿病足骨髓炎首例分离株的致病性和毒力。

Deciphering pathogenicity and virulence of the first isolate from diabetic foot osteomyelitis.

作者信息

Abi Najem Cynthia N, Magnan Chloé, Plumet Lucile, Ahmad-Mansour Nour, Pouget Cassandra, Morsli Madjid, Pantel Alix, Kissa Karima, Sotto Albert, Lavigne Jean-Philippe, Molle Virginie

机构信息

VBIC, INSERM U1047, University of Montpellier, Montpellier, France.

VBIC, INSERM U1047, University of Montpellier, Department of Microbiology and Hospital Hygiene, CHU Nîmes, Nîmes, France.

出版信息

Front Cell Infect Microbiol. 2024 Dec 17;14:1489280. doi: 10.3389/fcimb.2024.1489280. eCollection 2024.

Abstract

INTRODUCTION

This study identifies as a new coagulase-negative staphylococcal species isolated from diabetic foot osteomyelitis (DFOM) and provides an in-depth analysis of its pathogenic and virulence profile, as well as demonstrating its potential to cause infection.

METHODS

The NSD001 strain was examined for its planktonic growth, biofilm production, and phagocytosis rates in murine macrophages compared to NSA739. Additionally, persistence and replication within human osteoblasts were investigated, while the zebrafish embryo model was employed to assess virulence. Genomic sequencing and bioinformatic analysis were also conducted to identify genes associated with virulent potential.

RESULTS AND DISCUSSION

NSD001 exhibited robust planktonic growth and significant biofilm production, highlighting its capacity to initiate and maintain an infection, and demonstrated similar rates of phagocytosis as NSA739 in murine macrophages, suggesting a mechanism for evading initial host defenses. The strain persisted and replicated within human osteoblasts, indicative of a strategy for intracellular survival and facilitation of chronic osteomyelitis. The zebrafish embryo model revealed a slower, yet fatal, virulence profile for NSD001 compared to the rapid lethality induced by NSA739. Genomic sequencing and bioinformatic analysis uncovered various genes corroborating its virulence. NSD001 poses a significant concern in DFOM due to its ability to form biofilms and survive within host cells, presenting challenges for current treatment strategies. This underscores the need for updated clinical protocols and increased awareness among healthcare professionals to effectively manage infections caused by this emerging pathogen.

摘要

引言

本研究鉴定出一种从糖尿病足骨髓炎(DFOM)中分离出的新型凝固酶阴性葡萄球菌,并对其致病和毒力特征进行了深入分析,同时证明了其引起感染的可能性。

方法

与NSA739相比,检测了NSD001菌株在鼠巨噬细胞中的浮游生长、生物膜形成和吞噬率。此外,研究了其在人成骨细胞内的持久性和复制情况,同时采用斑马鱼胚胎模型评估毒力。还进行了基因组测序和生物信息学分析,以鉴定与毒力潜力相关的基因。

结果与讨论

NSD001表现出强劲的浮游生长和显著的生物膜形成,突出了其引发和维持感染的能力,并且在鼠巨噬细胞中显示出与NSA739相似的吞噬率,提示其逃避宿主初始防御的机制。该菌株在人成骨细胞内持续存在并复制,表明其具有细胞内存活和促进慢性骨髓炎的策略。斑马鱼胚胎模型显示,与NSA739诱导的快速致死性相比,NSD001的毒力特征较为缓慢但致命。基因组测序和生物信息学分析发现了各种证实其毒力的基因。由于NSD001能够形成生物膜并在宿主细胞内存活,因此在DFOM中引起了重大关注,给当前的治疗策略带来了挑战。这凸显了更新临床方案以及提高医护人员认识以有效管理由这种新兴病原体引起的感染的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f1a/11685071/b39cf1181731/fcimb-14-1489280-g001.jpg

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