Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72074 Tübingen, Germany.
Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany.
Viruses. 2022 Nov 8;14(11):2471. doi: 10.3390/v14112471.
asymptomatically colonizes the nasal cavity of mammals, but it is also a leading cause of life-threatening infections. Most human nasal isolates carry Sa3 phages, which integrate into the bacterial gene encoding a sphingomyelinase. The virulence factor-encoding genes carried by the Sa3-phages are highly human-specific, and most animal strains are Sa3 negative. Thus, both insertion and excision of the prophage could potentially confer a fitness advantage to . Here, we analyzed the phage life cycle of two Sa3 phages, Φ13 and ΦN315, in different phage-cured strains. Based on phage transfer experiments, strains could be classified into low (8325-4, SH1000, and USA300c) and high (MW2c and Newman-c) transfer strains. High-transfer strains promoted the replication of phages, whereas phage adsorption, integration, excision, or transcription was not significantly different between strains. RNASeq analyses of replication-deficient lysogens revealed no strain-specific differences in the CI/Mor regulatory switch. However, lytic genes were significantly upregulated in the high transfer strain MW2c Φ13 compared to strain 8325-4 Φ13. By transcriptional start site prediction, new promoter regions within the lytic modules were identified, which are likely targeted by specific host factors. Such host-phage interaction probably accounts for the strain-specific differences in phage replication and transfer frequency. Thus, the genetic makeup of the host strains may determine the rate of phage mobilization, a feature that might impact the speed at which certain strains can achieve host adaptation.
无症状定植于哺乳动物的鼻腔，但也是导致危及生命的感染的主要原因。大多数人类鼻腔分离株携带 Sa3 噬菌体，该噬菌体整合到细菌基因中，编码鞘磷脂酶。Sa3 噬菌体携带的编码毒力因子的基因高度具有人种特异性，大多数动物株系为 Sa3 阴性。因此，噬菌体的插入和切除都有可能给 带来适应性优势。在这里，我们分析了两种 Sa3 噬菌体，Φ13 和 ΦN315，在不同噬菌体消除的 株系中的噬菌体生命周期。基于噬菌体转移实验，可将菌株分为低（8325-4、SH1000 和 USA300c）和高（MW2c 和 Newman-c）转移菌株。高转移菌株促进了噬菌体的复制，而噬菌体吸附、整合、切除或转录在菌株之间没有显著差异。复制缺陷型溶原菌的 RNAseq 分析显示，CI/Mor 调控开关没有菌株特异性差异。然而，在高转移菌株 MW2c Φ13 中，裂解基因的表达水平明显高于菌株 8325-4 Φ13。通过转录起始位点预测，在裂解模块内识别到新的启动子区域，这些区域可能被特定的宿主因子靶向。这种宿主-噬菌体相互作用可能解释了噬菌体复制和转移频率的菌株特异性差异。因此，宿主菌株的遗传组成可能决定了噬菌体动员的速度，这一特征可能影响某些菌株实现宿主适应的速度。
