副猪链球菌中一种新基因Lsa（F）的特征，该基因赋予对胸膜切割素、林可酰胺和链菌素a的抗性

摘要(中文译文)

可转移的抗菌药物耐药性对公共卫生构成重大威胁。Lsa同源物介导的对截短侧耳素类、林可酰胺类和链阳菌素A（PLS）的耐药性进一步加剧了这一问题。本研究旨在鉴定并表征在副猪链球菌（Streptococcus parasuis）中发现的一种新型PLS耐药基因，命名为Lsa(F)。Lsa(F)蛋白与已知Lsa变体的序列一致性为41.9%–58.7%，并具有赋予核糖体保护作用的ATP结合盒（ABC）蛋白超家族F谱系所典型的结构特征。Lsa(F)在猪链球菌（Streptococcus suis）和金黄色葡萄球菌（Staphylococcus aureus）中的功能性表达赋予了对PLS的耐药性。尽管Lsa(F)基因在副猪链球菌分离株中的流行率相对较低，但数据库分析显示该基因主要存在于链球菌属和乳球菌属物种中。在链球菌属中，Lsa(F)基因主要与多种可移动遗传元件（MGEs）相关，包括质粒、整合接合元件（ICE）及ICE衍生元件；在乳球菌属中，该基因主要位于质粒上及特定的染色体位点。遗传背景分析发现，几乎在所有染色体MGEs和质粒上的Lsa(F)下游均存在插入序列ISLll1，提示其可能促进该基因移动的潜在机制。值得注意的是，我们的结果表明Lsa(F)基因可从副猪链球菌转移至猪链球菌，凸显了其向其他病原体传播的风险。因此，有必要加强对Lsa(F)基因的监测和流行病学监控，以降低其传播所带来的潜在公共卫生风险。

Abstract

Transferable antimicrobial resistance poses significant threats to public health. This issue is further exacerbated by Lsa homolog-mediated resistance to pleuromutilins, lincosamides, and streptogramin A (PLS). This study aimed to characterize a novel PLS resistance gene, designated Lsa(F), identified in Streptococcus parasuis. The Lsa(F) protein exhibits 41.9-58.7% sequence identity with known Lsa variants and shares structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that confers ribosome protection. Functional expression of Lsa(F) in Streptococcus suis and Staphylococcus aureus confers resistance to PLS. Although the prevalence of the Lsa(F) gene among S. parasuis isolates was found to be relatively low, database analyses revealed that this gene is primarily present in Streptococcus and Lactococcus species. In Streptococcus, the Lsa(F) gene is predominantly associated with various mobile genetic elements (MGEs), including plasmids, integrative and conjugative elements (ICE), and ICE-derived elements; in Lactococcus, it is primarily located on plasmids and at a specific chromosomal locus. Examination of the genetic context analysis identified the insertion sequence ISLll1 downstream of Lsa(F) on almost all chromosomal MGEs and plasmids, suggesting a potential mechanism facilitating its movement. Notably, our results indicate that the Lsa(F) gene can be transferred from S. parasuis to Streptococcus suis, highlighting a risk of its spread to other pathogens. Therefore, it is necessary to enhance surveillance and epidemiological monitoring of the Lsa(F) gene to reduce the potential public health risks associated with its spread.

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