Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Toxins (Basel). 2020 Aug 12;12(8):516. doi: 10.3390/toxins12080516.
is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator () locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host. Moreover, the Agr system is subject to complex crosstalk with other regulatory systems, including SaeRS and SrrAB, which can significantly impact the progression of osteomyelitis. The objective of this review is to highlight Agr regulation, its implications on toxin production, factors that affect Agr activation, and the potential paradoxical influences of Agr regulation on disease progression during osteomyelitis.
是一种革兰氏阳性病原体，能够感染几乎所有的脊椎动物器官。在这些组织中，骨（骨髓炎）的侵袭性感染尤为常见，并导致高发病率。骨髓炎的治疗非常困难，通常需要切除病变骨，并结合长期抗生素治疗来解决感染。在骨髓炎中，会在骨内的特定小生境中形成特征性的多细胞微菌落。这些多细胞微菌落中的毒力和代谢反应部分通过辅助基因调节（）基因座进行群体感应来协调，这允许葡萄球菌种群产生毒素并根据细菌密度进行适应。在骨髓炎中，Agr 系统显著促进了骨骼内稳态的失调和疾病的严重程度，但也可能反常地抑制其在宿主中的持续存在。此外，Agr 系统受到与其他调节系统（包括 SaeRS 和 SrrAB）的复杂交叉对话的影响，这可能会显著影响骨髓炎的进展。本综述的目的是强调 Agr 调节及其对毒素产生的影响、影响 Agr 激活的因素，以及 Agr 调节对骨髓炎进展中疾病进展的潜在矛盾影响。
