The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

中文翻译：

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来自印度次大陆的多重耐药性、社区相关的耐甲氧西林金黄色葡萄球菌谱系的进化和全球传播。


革兰氏阴性菌和卫生保健相关流行病病原体的抗菌药物耐药性的演变和全球传播已得到充分记录，这些病原体通常出现在抗菌药物大量使用的地区。然而，在社区环境中革兰氏阳性菌发生类似过程的程度尚不清楚。在这项研究中，我们追踪了印度次大陆孟加拉湾克隆 (ST772) 的多重耐药性、与社区相关的金黄色葡萄球菌谱系的最新起源和全球传播。我们生成了来自 14 个国家的 340 个分离株的全基因组序列数据，其中包括来自孟加拉国和印度的首批分离株，以重建该谱系的进化历史和基因组流行病学。我们的数据显示，该克隆于 20 世纪 60 年代初出现在印度次大陆，并在 90 年代迅速传播。洲际传播后，社区和卫生保健机构会出现短期暴发，通常与次大陆的旅行和家庭接触有关，但持续的地方性传播并不常见。获得多药耐药性整合质粒有助于 20 世纪 90 年代初期出现单一显性且全球传播的进化枝。生物膜、生长和毒性的表型数据表明抗菌素耐药性是 ST772 进化的驱动力。因此，孟加拉湾克隆结合了传统医疗保健相关克隆的多重耐药性和社区相关耐甲氧西林金黄色葡萄球菌 (MRSA) 的流行病学传播。我们的研究证明了全基因组测序对于追踪新出现的耐药病原体进化的重要性。 它为在印度次大陆和其他地方持续监测该克隆提供了一个关键框架。 重要性 孟加拉湾克隆 (ST772) 是一种与社区相关且具有多重耐药性的金黄色葡萄球菌谱系，于 2004 年首次从孟加拉国和印度分离出来。 ，我们发现孟加拉湾克隆体是从印度次大陆流行的剧毒祖先中产生的。其随后的全球传播与该地区的旅行或家庭接触有关。 ST772以有限的适应性成本逐渐获得了特定的抗性元素，并继续向全球出口，导致小规模的社区和医疗保健暴发。因此，孟加拉湾克隆将社区相关克隆的毒力潜力和流行病学与医疗保健相关金黄色葡萄球菌谱系的多药耐药性结合起来。这项研究证明了全基因组测序对于监测高度抗生素耐药病原体的重要性，这种病原体可能出现在抗生素管理不力地区的社区环境中，并迅速传播到世界各地的医院和社区。