A carbon dioxide-dependent small-colony variant of Escherichia coli SH4888 was isolated from blood cultures of a patient with cholangitis. To date, little is known regarding the molecular mechanisms leading to formation of carbon dioxide-dependent phenotypes in clinical isolates, but abnormalities in the carbonic anhydrase are thought to cause carbon dioxide autotrophy. In this study DNA sequence analysis of the carbonic anhydrase-encoding can locus in the carbon dioxide-dependent E. coli SH4888 revealed that the isolate had a 325-bp deletion spanning from the 3′-terminal region of can to the 3′-terminal region of hpt, which encodes a hypoxanthine phosphoribosyltransferase. To confirm that the carbon dioxide-dependent SCV phenotype of E. coli SH4888 was due to the can mutation, we performed a complementation test with a plasmid carrying an intact can that restored the normal phenotype. However, E. coli SH4888 had increased virulence compared to the can-complemented E. coli SH4888 in a murine infection model. In conclusion, these data confirm that impaired carbonic anhydrase function can cause a carbon dioxide-dependent SCV phenotype in E. coli SH4888 and provides a fitness advantage in terms of infection.

从患有胆管炎的患者的血液培养物中分离出大肠杆菌SH4888的二氧化碳依赖性小菌落变体。迄今为止，关于导致临床分离物中形成二氧化碳依赖性表型的分子机制知之甚少，但据认为碳酸酐酶异常会导致二氧化碳自养。在这项研究中，碳酸酐酶编码罐的DNA序列分析位于二氧化碳依赖性大肠杆菌SH4888中，结果表明该分离株具有一个325 bp的缺失，范围从罐的3'末端区域到3'末端hpt区域，编码次黄嘌呤磷酸核糖基转移酶。为了确认大肠杆菌SH4888的依赖二氧化碳的SCV表型是由于can突变引起的，我们对带有完整罐的质粒进行了互补测试，该罐恢复了正常的表型。但是，大肠杆菌SH4888增加了毒力相比罐-complemented大肠杆菌SH4888在鼠感染模型。总之，这些数据证实，碳酸酐酶功能受损会导致大肠杆菌SH4888中的二氧化碳依赖性SCV表型，并在感染方面提供合适的优势。