The genotoxin colibactin is a determinant of virulence in Escherichia coli K1 experimental neonatal systemic infection. Escherichia coli K1 colibactin

Escherichia coli K1 strains are a major cause of sepsis and meningitis in neonates. Here, we show that all but one of 36 E. coli K1 neonatal isolates carry clbA and clbP, genes required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes genomic instability in eukaryotic cells by induction of double-strand breaks in DNA. Inactivation of clbA and clbP in E. coli A192PP, a virulent K1 strain that colonizes the gastrointestinal tract and translocates to the blood compartment with very high frequency in experimental infection of the neonatal rat, significantly reduced the capacity of A192PP to colonize the gut, engender double-strand breaks in DNA and cause invasive, lethal disease. Restoration of colibactin gene function by complementation re-established the fully virulent phenotype. We conclude that colibactin contributes to the capacity of E. coli K1 to cause invasive disease in the susceptible neonate.

大肠杆菌K1（Escherichia coli K1）菌株是新生儿败血症与脑膜炎的主要致病菌。本研究发现，36株新生儿来源的大肠杆菌K1分离株中，除1株外其余均携带clbA与clbP基因；这两个基因为大肠杆菌素（colibactin）的合成所必需——大肠杆菌素是一类聚酮肽类基因毒素，可通过诱导真核细胞DNA双链断裂引发基因组不稳定。在强致病性大肠杆菌K1菌株A192PP中失活clbA与clbP基因后——该菌株可定殖新生大鼠胃肠道，并在新生大鼠实验性感染模型中以极高频率移位至血液系统——A192PP的肠道定殖能力、诱导DNA双链断裂的能力以及引发侵袭性致死性疾病的能力均显著下降。通过互补实验恢复大肠杆菌素相关基因功能后，菌株的完全致病性表型得以重建。本研究结论表明，大肠杆菌素可增强大肠杆菌K1引发易感新生儿侵袭性疾病的能力。