Precisely modulated pathogenicity island interference with late phage gene transcription
Precisely modulated pathogenicity island interference with late phage gene transcription
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DOI：
10.1073/pnas.1406749111
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发表时间：
2014-10-07
影响因子：
11.1
通讯作者：
Novick, Richard P.
中科院分区：
文献类型：
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作者：
Ram, Geeta;Chen, John;Novick, Richard P.
经过漫长的进化，细菌已经形成了针对噬菌体生命周期各个方面的耐药机制。大多数与噬菌体抗性相关的基因由质粒和其他可移动遗传元件携带，包括噬菌体及其亲属。噬菌体抗性的一个非常特殊的例子是高度移动的噬菌体卫星，即葡萄球菌致病岛（SaPI），它携带并传播超抗原和其他毒力基因。与通常的噬菌体抗性机制不同，SaPI 编码的干扰机制经过精心设计，以确保被噬菌体感染的、含有 SaPI 的细胞裂解，释放所需的 SaPI 颗粒以及大大减少的噬菌体颗粒。先前描述的 SaPI 干扰基因针对 SaPI 颗粒生产和释放不需要的噬菌体功能。在这里，我们描述了 SaPI 介导的干扰系统，该系统影响晚期噬菌体基因转录的表达，因此是 SaPI 和噬菌体所必需的。虽然单独克隆时，单个 SaPI 基因完全阻止噬菌体产生，但其原位活性由第二个基因精确调节，从而达到所需的干扰水平。对于宿主细菌来说，SaPI 的优势在于可以抑制噬菌体的过度生长，同时增强其基因转移活性。这种活性与成簇的规则间隔短回文重复序列 (CRISPR) 的活性相反，后者以噬菌体介导的基因转移为代价完全阻止噬菌体生长。在葡萄球菌中，SaPI 策略似乎在进化过程中盛行：绝大多数金黄色葡萄球菌菌株携带一种或多种 SaPI，而 CRISPR 极其罕见。
Having gone to great evolutionary lengths to develop resistance to bacteriophages, bacteria have come up with resistance mechanisms directed at every aspect of the bacteriophage life cycle. Most genes involved in phage resistance are carried by plasmids and other mobile genetic elements, including bacteriophages and their relatives. A very special case of phage resistance is exhibited by the highly mobile phage satellites, staphylococcal pathogenicity islands (SaPIs), which carry and disseminate superantigen and other virulence genes. Unlike the usual phage-resistance mechanisms, the SaPI-encoded interference mechanisms are carefully crafted to ensure that a phage-infected, SaPI-containing cell will lyse, releasing the requisite crop of SaPI particles as well as a greatly diminished crop of phage particles. Previously described SaPI interference genes target phage functions that are not required for SaPI particle production and release. Here we describe a SaPI-mediated interference system that affects expression of late phage gene transcription and consequently is required for SaPI and phage. Although when cloned separately, a single SaPI gene totally blocks phage production, its activity in situ is modulated accurately by a second gene, achieving the required level of interference. The advantage for the host bacteria is that the SaPIs curb excessive phage growth while enhancing their gene transfer activity. This activity is in contrast to that of the clustered regularly interspaced short palindromic repeats (CRISPRs), which totally block phage growth at the cost of phage-mediated gene transfer. In staphylococci the SaPI strategy seems to have prevailed during evolution: The great majority of Staphylococcus aureus strains carry one or more SaPIs, whereas CRISPRs are extremely rare.