Staphylococcal pathogenicity islands (SaPIs) are a family of closely related mobile chromosomal islands that encode and disseminate the superantigen toxins, toxic shock syndrome toxin 1 and superantigen enterotoxin B (SEB). They are regulated by master repressors, which are counteracted by helper phage–encoded proteins, thereby inducing their excision, replication, packaging and intercell transfer. SaPIs are major components of the staphylococcal mobilome, occupying five chromosomal att sites, with many strains harbouring two or more. As regulatory interactions between co-resident SaPIs could have profound effects on the spread of superantigen pathobiology, we initiated the current study to search for such interactions. Using classical genetics, we found that, with one exception, their regulatory systems do not cross-react. The exception was SaPI3, which was originally considered defective because it could not be mobilized by any known helper phage. We show here that SaPI3 has an atypical regulatory module and is induced not by a phage but by many other SaPIs, including SaPI2, SaPIbov1 and SaPIn1, each encoding a conserved protein, Sis, which counteracts the SaPI3 repressor, generating an intracellular regulatory cascade: the co-resident SaPI, when conventionally induced by a helper phage, expresses its sis gene which, in turn, induces SaPI3, enabling it to spread. Using bioinformatics analysis, we have identified more than 30 closely related coancestral SEB-encoding SaPI3 relatives occupying the same att site and controlled by a conserved regulatory module, immA–immR–str′. This module is functionally analogous but unrelated to the typical SaPI regulatory module, stl–str. As SaPIs are phage satellites, SaPI3 and its relatives are SaPI satellites.

葡萄球菌致病岛 (SaPIs) 是一个密切相关的移动染色体岛家族，它们编码和传播超抗原毒素、中毒性休克综合征毒素 1 和超抗原肠毒素 B (SEB)。它们受主阻遏物的调节，被辅助噬菌体编码的蛋白质抵消，从而诱导它们的切除、复制、包装和细胞间转移。SaPIs 是葡萄球菌移动组的主要成分，占据五个染色体位点，许多菌株含有两个或更多。由于共同驻留 SaPI 之间的监管相互作用可能对超抗原病理生物学的传播产生深远影响，我们启动了当前的研究来寻找这种相互作用。使用经典遗传学，我们发现，除了一个例外，它们的调节系统不会发生交叉反应。SaPI3 是个例外，它最初被认为是有缺陷的，因为它不能被任何已知的辅助噬菌体动员。我们在这里展示了 SaPI3 具有非典型调节模块，并且不是由噬菌体诱导，而是由许多其他 SaPI 诱导，包括 SaPI2、SaPIbov1 和 SaPIn1，它们各自编码一种保守的蛋白质 Sis，它抵消 SaPI3 阻遏物，产生细胞内调节级联反应：当常规由辅助噬菌体诱导时，共同驻留的 SaPI 表达其sis基因反过来诱导 SaPI3，使其能够传播。使用生物信息学分析，我们已经确定了 30 多个密切相关的编码 SAPI3 的同祖 SEB 亲属，它们占据相同的att位点并由保守的调节模块immA-immR-str '控制。该模块在功能上与典型的 SaPI 监管模块stl–str类似但无关。由于 SaPIs 是噬菌体卫星，所以 SaPI3 及其亲属是 SaPI 卫星。