NEISSERIA-GONORRHOEAE HEME BIOSYNTHETIC MUTANTS UTILIZE HEME AND HEMOGLOBIN AS A HEME SOURCE BUT FAIL TO GROW WITHIN EPITHELIAL-CELLS

Many bacterial pathogens, including pathogenic neisseriae, can use hem e 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). Th e hemH mutant failed to grow without an exogenous supply of heme or he moglobin, whereas the hemA mutant failed to grow unless heme, hemoglob in, or heme precursors were present. Growth of the mutants with hemogl obin required expression of the hemoglobin receptor (HpuAB) and was To nB dependent. However, growth with heme required neither HpuAB nor Ton B. An fbpA mutant grew normally when either heme or hemoglobin was pre sent in the medium. The heme biosynthetic mutants showed reduced intra cellular survival, compared to the parent strain, within A-431 endocer vical epithelial fell cultures. These studies demonstrate that in addi tion to synthesizing their own heme, N. gonorrhoeae strains are able t o internalize and utilize exogenous heme independently of FbpA but app ear unable to obtain heme from within epithelial cells for growth.