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 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.
Turner
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Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA. pturner@med.unc.edu
Thomas
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Elkins
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Clary
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Sparling
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D000445:Aldehyde Oxidoreductases / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D002584:Cervix Uteri; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D006418:Heme / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000382:microbiology / Q000502:physiology; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D016297:Mutagenesis, Site-Directed; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D033902:Periplasmic Binding Proteins; D010641:Phenotype
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006454:Hemoglobins; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D006418:Heme; D007501:Iron; D000445:Aldehyde Oxidoreductases; C067282:glutamyl tRNA reductase