Table_3_Clinical Staphylococcus argenteus Develops to Small Colony Variants to Promote Persistent Infection.pdf

Staphylococcus argenteus is a novel staphylococcal species (also considered as a part of Staphylococcus aureus complex) that is infrequently reported on, and clinical S. argenteus infections are largely unstudied. Here, we report a persistent and recurrent hip joint infection case in which a S. argenteus strain and its small colony variants (SCVs) strain were successively isolated. We present features of the two S. argenteus strains and case details of their pathogenicity, explore factors that induce S. argenteus SCVs formation in the course of anti-infection therapy, and reveal potential genetic mechanisms for S. argenteus SCVs formation. S. argenteus strains were identified using phenotypic and genotypic methods. The S. argenteus strain XNO62 and SCV strain XNO106 were characterized using different models. S. argenteus SCVs were induced by the administration of amikacin and by chronic infection course based on the clinical case details. The genomes of both strains were sequenced and aligned in a pair-wise fashion using Mauve. The case details gave us important insights on the characteristics and therapeutic strategies for infections caused by S. argenteus and its SCVs. We found that strain XNO62 and SCV strain XNO106 are genetically-related sequential clones, the SCV strain exhibits reduced virulence but enhanced intracellular persistence compared to strain XNO62, thus promoting persistent infection. The induction experiments for S. argenteus SCVs demonstrated that high concentrations of amikacin greatly induce S. argenteus XNO62 to form SCVs, while a chronic infection of S. argenteus XNO62 slightly induces SCVs formation. Potential genetic mechanisms for S. argenteus SCVs formation were revealed and discussed based on genomic alignments. In conclusion, we report the first case of infection caused by S. argenteus and its SCVs strain. More attention should be paid to infections caused by S. argenteus and its SCVs, as they constitute a challenge to current therapeutic strategies. The problem of S. argenteus SCVs should be noticed, in particular when amikacin is used or in the case of a chronic S. argenteus infection.

银色葡萄球菌（亦被视为金黄色葡萄球菌复合体的一部分）是一种罕见报道的新型葡萄球菌属，其临床感染病例研究甚少。本研究报道了一例持续的髋关节感染病例，其中成功分离出银色葡萄球菌菌株及其小菌落变异（SCVs）菌株。我们详细介绍了两种银色葡萄球菌菌株的特征及其致病性案例细节，探讨了抗感染治疗过程中诱发银色葡萄球菌SCVs形成的相关因素，并揭示了银色葡萄球菌SCVs形成的潜在遗传机制。通过表型及基因型方法对银色葡萄球菌菌株进行鉴定。使用不同模型对银色葡萄球菌菌株XNO62及其SCV菌株XNO106进行了特征描述。基于临床案例细节，通过使用阿米卡星及慢性感染过程诱导银色葡萄球菌SCVs的形成。利用Mauve软件对两种菌株的基因组进行成对序列比对。案例细节为我们提供了关于银色葡萄球菌及其SCVs引起的感染的特性及治疗策略的重要见解。研究发现，菌株XNO62及其SCV菌株XNO106为遗传相关的连续克隆，与菌株XNO62相比，SCV菌株展现出降低的致病性但增强了细胞内持久性，从而促进了持续感染。银色葡萄球菌SCVs的诱导实验表明，高浓度的阿米卡星极大地诱导银色葡萄球菌XNO62形成SCVs，而慢性银色葡萄球菌XNO62感染轻微地诱导SCVs形成。基于基因组比对，揭示了银色葡萄球菌SCVs形成的潜在遗传机制并进行了讨论。总之，我们首次报道了由银色葡萄球菌及其SCVs菌株引起的感染案例。应更加关注由银色葡萄球菌及其SCVs引起的感染，因为它们构成了对当前治疗策略的挑战。特别是在使用阿米卡星或慢性银色葡萄球菌感染的情况下，应特别注意银色葡萄球菌SCVs的问题。