Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from lactoferrin

Abstract

The ability of 107 Neisseria isolates to compete for iron with human lactoferrin (LF) was examined. Each of 15 meningococci, 53% of 59 selected gonococci, and 24% of 33 commensal Neisseria could use LF-bound iron for growth. Isolates which could not obtain iron from LF were growth inhibited when sufficient LF was added to defined agar medium to bind available free iron. No difference was observed in the ability of colony type 1 and colony type 4 gonococci of the same strain to compete with LF for iron. LF was growth inhibitory for 50%o of 22 disseminated disease isolates (DGI strains) and 51% of 35 local urogenital disease isolates (UGI strains). Only 14% of gonococcal isolates requiring arginine, hypoxanthine, and uracil for growth were able to compete with LF for iron, whereas 87% of all other gonococcal isolates could do so (P < 0.005). Ability to obtain iron from LF does not appear to be required for survival of Neisseria on mucosal surfaces, nor essential for invasion of the bloodstream by gonococci. However, ability to utilize LF as a source of iron may contribute to differences in pathogenicity among certain gonococcal isolates.

Iron uptake mechanisms of pathogenic bacteria

“…Chicken ovotransferrin is not an iron source for Neisseria species [92], despite a high degree of homology with human transferrin [31], and in competitive solid phase dot binding assays rabbit, horse and bovine transferrins were unable to compete with human transferrin for binding to receptors [95]. Pathogenic Neisseria species also utilise human lactoferrin as an iron source [94][95][96][97], while most non-pathogenic species are unable to utilise either iron-binding protein [92,93,98]. The receptors for transferrin and lactoferrin in these species are distinct since neither protein is capable of blocking the binding of the other in solid phase dot binding assays [99,100].…”

Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and exbD genes

“…These include obtaining iron directly from TF and LF or indirectly by a siderophore-mediated process (reviewed by Mietzner and Morse, 1994). Although pathogenic Neisseria species do not synthesize soluble siderophores (Norrod and Williams, 1978;Archibald and DeVoe, 1979;West and Sparling, 1985), all are able to utilize TF and many are able to utilize LF as iron sources (Mickelsen et al, 1981;1982;McKenna et al, 1988). They are also capable of using haemin (HM) and haemoglobin (HB) (Mickelsen et al, 1981;Chen et al, 1996), haemoglobinhaptoglobin (HB-HP) complexes (Lewis and Dyer, 1995) and certain siderophores produced by other bacteria (West and Sparling, 1987).…”

The ferric iron‐binding protein of pathogenic Neisseria spp. functions as a periplasmic transport protein in iron acquisition from human transferrin

“…can be attributed, in part, to the efficiency with which these organisms obtain iron within the ironrestricted environment of the host (Archibald and DeVoe, 1979;Simonson et al, 1982). Phenotypically, these pathogens overcome the host-imposed iron barrier by a novel mechanism that does not involve the production of a classical siderophore (Norrod and Williams, 1978;Mickelsen and Sparling, 1981;Mickelsen et al, 1982;West and Sparling, 1985). In contrast, this mechanism utilizes distinct cell-surface receptors that specifically recognize human transferrin or lactoferrin (Mietzner and Morse, 1983;Schryvers and Morris, 1988a,b;Lee and Schryvers, 1988;Tsai etal., 1988;Blanton etai, 1990).…”