Department of Medicine, Division of Infectious Diseases, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
mBio. 2012 Feb 28;3(2). doi: 10.1128/mBio.00027-12. Print 2012.
A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage ϕ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans.
Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.
一种被称为 ST398 的耐甲氧西林金黄色葡萄球菌（MRSA）克隆体已成为与牲畜密切接触的个体中急性感染的主要原因。最近，在多个国家已经记录到一种动物无关的 ST398 甲氧西林敏感金黄色葡萄球菌（MSSA）克隆体的出现。然而，对 MSSA 的有限监测使得无法准确评估 ST398 的全球传播及其临床相关性。在这里，我们提供的证据表明，ST398 是曼哈顿北部 MSSA 感染的常见来源，并且在家庭中的个体之间易于传播。这与人与人之间传播的与牲畜相关的 ST398（LA-ST398）MRSA 菌株的有限传染性形成对比。我们的全基因组序列分析表明，人类相关的 ST398 MSSA 克隆体的染色体小于 LA-ST398 MRSA 参考菌株 S0385 的染色体，这主要是由于较少的移动遗传元件（MGEs）。相比之下，人类 ST398 MSSA 分离株携带噬菌体 ϕ3 和人类特异性免疫逃逸簇（IEC）基因 chp 和 scn。虽然人类 ST398 MSSA 克隆体和 S0385 之间的核心基因组大部分是保守的，但这些菌株在完整粘附基因的 repertoire 和组成上存在显著差异。这些遗传变化与人类 ST398 MSSA 分离株对人皮肤角质形成细胞和角蛋白的粘附能力显著增强有关。我们提出，人类 ST398 MSSA 克隆体可以通过优化的 MGE 和粘附分子 repertoire 传播，这些 MGE 和粘附分子适应于人与人之间的传播，从而独立于动物接触而传播。
金黄色葡萄球菌菌株通常被认为是种特异性的。然而，已经报道了从猪到人类的金黄色葡萄球菌克隆体（例如 ST398）的跨物种转移。最近，我们观察到 ST398 作为一种定植菌在曼哈顿北部的人类中出现。在这里，我们报告 ST398 是这种城市环境中 MSSA 感染的常见原因。ST398 MSSA 克隆体在家庭内易于传播，与动物接触无关。我们发现，由于移动遗传元件较少，人类 ST398 MSSA 基因组小于 LA-ST398 菌株 S0385。人类和 LA-ST398 菌株在粘附基因的组成及其与人类皮肤角质形成细胞结合的能力上也存在差异，为金黄色葡萄球菌宿主适应提供了潜在的机制。我们的研究结果表明，鉴于 ST398 MSSA 快速且临床未检测到的传播证据，对 MSSA 进行分子监测非常重要。
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