Turner P C, Thomas C E, Elkins C, Clary S, Sparling P F
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Infect Immun. 1998 Nov;66(11):5215-23. doi: 10.1128/IAI.66.11.5215-5223.1998.
Many bacterial pathogens, including pathogenic neisseriae, can use heme as an iron source for growth. To study heme utilization by Neisseria gonorrhoeae, two heme biosynthetic mutants were constructed, one with a mutation in hemH (the gene encoding ferrochelatase) and one with a mutation in hemA (the gene encoding gamma-glutamyl tRNA reductase). The hemH mutant failed to grow without an exogenous supply of heme or hemoglobin, whereas the hemA mutant failed to grow unless heme, hemoglobin, or heme precursors were present. Growth of the mutants with hemoglobin required expression of the hemoglobin receptor (HpuAB) and was TonB dependent. However, growth with heme required neither HpuAB nor TonB. An fbpA mutant grew normally when either heme or hemoglobin was present in the medium. The heme biosynthetic mutants showed reduced intracellular survival, compared to the parent strain, within A-431 endocervical epithelial cell cultures. These studies demonstrate that in addition to synthesizing their own heme, N. gonorrhoeae strains are able to internalize and utilize exogenous heme independently of FbpA but appear unable to obtain heme from within epithelial cells for growth.
许多细菌病原体，包括致病性奈瑟菌，都可以利用血红素作为生长所需的铁源。为了研究淋病奈瑟菌对血红素的利用情况，构建了两个血红素生物合成突变体，一个在hemH（编码铁螯合酶的基因）中发生突变，另一个在hemA（编码γ-谷氨酰tRNA还原酶的基因）中发生突变。hemH突变体在没有外源血红素或血红蛋白供应的情况下无法生长，而hemA突变体除非有血红素、血红蛋白或血红素前体存在否则无法生长。突变体利用血红蛋白生长需要血红蛋白受体（HpuAB）的表达，并且依赖于TonB。然而，利用血红素生长既不需要HpuAB也不需要TonB。当培养基中存在血红素或血红蛋白时，fbpA突变体生长正常。与亲本菌株相比，血红素生物合成突变体在A-431宫颈上皮细胞培养物中的细胞内存活率降低。这些研究表明，除了合成自身的血红素外，淋病奈瑟菌菌株能够独立于FbpA内化并利用外源血红素，但似乎无法从上皮细胞内获取血红素用于生长。
