<p>Prophages in the <i>E. coli</i> NC101 chromosome.</p>

Prophages are prevalent features of bacterial genomes that can reduce susceptibility to infection by competing phages, yet the mechanisms involved are often elusive. Here, we identify a small RNA (svsR) encoded by the lambdoid prophage NC-SV in adherent-invasive Escherichia coli strain NC101 that limits infection by virulent coliphages. Comparative genomics revealed that NC-SV–like prophages and svsR homologs are broadly conserved across Enterobacteriaceae. Transcriptomic analyses show that svsR represses maltodextrin transport genes, including lamB, which encodes the outer membrane maltoporin LamB, a known receptor for numerous coliphages. Deletion of the lamB gene reveals that while LamB is not required for replication of the virulent phages tested, it contributes to plaque expansion, indicating a role in phage spread but not as an essential receptor. Nutrient supplementation experiments further linked maltodextrin and glucose availability to changes in plaque expansion and phage adsorption. In vivo, we compared wild-type NC101 and a prophage-deletion strain (NC101∆NC-SV) in mice to assess the impact of NC-SV on lytic phage susceptibility. Although intestinal E. coli densities remained stable across groups, animals colonized with NC101 exhibited markedly reduced phage burdens in both the intestinal lumen and mucosa compared to mice colonized with NC101∆NC-SV. This reduced phage pressure was associated with increased dissemination of E. coli to extraintestinal tissues, including the spleen and liver. Together, these findings highlight a nutrient-responsive, prophage-encoded mechanism that protects E. coli from phage predation and may promote bacterial persistence in and dissemination from the mammalian gut.前噬菌体（prophage）是细菌基因组中普遍存在的特征，可降低宿主菌对竞争性噬菌体感染的易感性，但其潜在分子机制往往尚不明确。本研究从粘附侵袭性大肠杆菌（adherent-invasive Escherichia coli）NC101菌株的λ样前噬菌体（lambdoid prophage）NC-SV中，鉴定出一种小RNA（small RNA）svsR，其可减弱强毒性大肠杆菌噬菌体（coliphage）的感染能力。比较基因组学分析显示，类似NC-SV的前噬菌体与svsR同源基因在肠杆菌科（Enterobacteriaceae）中广泛保守。转录组分析表明，svsR可抑制麦芽糖转运相关基因的表达，其中包括lamB基因——该基因编码外膜麦芽糖孔蛋白（maltoporin）LamB，后者是多种大肠杆菌噬菌体的已知受体。lamB基因敲除实验结果显示，尽管LamB并非受试强毒性噬菌体复制所必需，但它可促进噬斑（plaque）的扩增，表明其在噬菌体传播中发挥作用，但并非噬菌体复制的必需受体。营养补充实验进一步证实，麦芽糖糊精与葡萄糖的可利用性与噬斑扩增及噬菌体吸附能力的变化密切相关。体内实验中，我们以小鼠为模型，比较了野生型NC101与前噬菌体缺失菌株NC101ΔNC-SV的定植差异，以评估NC-SV对裂解性噬菌体（lytic phage）易感性的影响。尽管各组小鼠肠道内大肠杆菌的定植密度无显著差异，但与定植NC101ΔNC-SV的小鼠相比，定植野生型NC101的小鼠肠道内腔与黏膜内的噬菌体载量均显著降低。噬菌体压力的降低与大肠杆菌向脾、肝等肠外组织的播散增加显著相关。综上，本研究结果揭示了一种由前噬菌体编码、可响应营养信号的分子机制，该机制可保护大肠杆菌免受噬菌体捕食，并可能促进细菌在哺乳动物肠道内的定植与向外播散。