钟鸣 (2023-03-31 22:47):
#paper doi:10.1128/iai.00529-22 Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone 过去的研究中发现高血糖患者更容易发生严重的金黄色葡萄球菌感染,这是一种广泛存在于环境中且具有重要公共卫生意义的细菌。为了这种现象的原因,研究者使用小鼠作为实验动物,构建了高血糖模型,同时使用转座子测序技术对金黄色葡萄球菌随机插入突变,随后攻毒检验毒力。实验结果是得到一个基因,sodA ,编码超氧化物歧化酶 A,与该菌在高糖环境下的毒力增加有关。从技术和研究方案来说很成熟很简单,但是得到的结论很有价值且深远。但该基因如何影响金黄色葡萄球菌在特定环境下的表型,以及这种调控是否具有种属特异性、该基因是否具有未探明的功能,仍然未知。当然还需要更多的实验从不同角度验证本文的结论。
IF:2.900Q2 Infection and immunity, 2023-04-18. DOI: 10.1128/iai.00529-22 PMID: 36877063
Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone
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Abstract:
Hyperglycemia, or elevated blood glucose, renders individuals more prone to developing severe Staphylococcus aureus infections. S. aureus is the most common etiological agent of musculoskeletal infection, which is a common manifestation of disease in hyperglycemic patients. However, the mechanisms by which S. aureus causes severe musculoskeletal infection during hyperglycemia are incompletely characterized. To examine the influence of hyperglycemia on S. aureus virulence during invasive infection, we used a murine model of osteomyelitis and induced hyperglycemia with streptozotocin. We discovered that hyperglycemic mice exhibited increased bacterial burdens in bone and enhanced dissemination compared to control mice. Furthermore, infected hyperglycemic mice sustained increased bone destruction relative to euglycemic controls, suggesting that hyperglycemia exacerbates infection-associated bone loss. To identify genes contributing to S. aureus pathogenesis during osteomyelitis in hyperglycemic animals relative to euglycemic controls, we used transposon sequencing (TnSeq). We identified 71 genes uniquely essential for S. aureus survival in osteomyelitis in hyperglycemic mice and another 61 mutants with compromised fitness. Among the genes essential for S. aureus survival in hyperglycemic mice was the gene encoding superoxide dismutase A (), one of two S. aureus superoxide dismutases involved in detoxifying reactive oxygen species (ROS). We determined that a mutant exhibits attenuated survival in high glucose and during osteomyelitis in hyperglycemic mice. SodA therefore plays an important role during growth in high glucose and promotes S. aureus survival in bone. Collectively, these studies demonstrate that hyperglycemia increases the severity of osteomyelitis and identify genes contributing to S. aureus survival during hyperglycemic infection.
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