Abstract
Neisseria meningitidis can utilize haem, haemoglobin and haemoglobin–haptoglobin complexes as sources of iron via two TonB-dependent phase variable haemoglobin receptors, HmbR and HpuAB. HmbR is over-represented in disease isolates, suggesting a link between haemoglobin acquisition and meningococcal disease. This study compared the distribution of HpuAB and phase variation (PV) status of both receptors in disease and carriage isolates. Meningococcal disease (n = 214) and carriage (n = 305) isolates representative of multiple clonal complexes (CCs) were investigated for the distribution, polyG tract lengths and ON/OFF status of both haemoglobin receptors, and for the deletion mechanism for HpuAB. Strains with both receptors or only hmbR were present at similar frequencies among meningococcal disease isolates as compared with carriage isolates. However, >90 % of isolates from the three CCs CC5, CC8 and CC11 with the highest disease to carriage ratios contained both receptors. Strains with an hpuAB-only phenotype were under-represented among disease isolates, suggesting selection against this receptor during systemic disease, possibly due to the receptor having a high level of immunogenicity or being inefficient in acquisition of iron during systemic spread. Absence of hpuAB resulted from either complete deletion or replacement by an insertion element. In an examination of PV status, one or both receptors were found in an ON state in 91 % of disease and 71 % of carriage isolates. We suggest that expression of a haemoglobin receptor, either HmbR or HpuAB, is of major importance for systemic spread of meningococci, and that the presence of both receptors contributes to virulence in some strains.
Highlights
Neisseria meningitidis is an obligate commensal of humans, residing in the nasopharynx of 10–30 % of individuals
Complete sequences of hpuA were generated for a serogroup B isolate and isolates representing the following clonal complexes (CCs): 23, 60, 167 and 174
As nothing is known about the functional domains of this protein, it is unclear whether this variability will influence its functions or antigenicity
Summary
Neisseria meningitidis (the meningococcus) is an obligate commensal of humans, residing in the nasopharynx of 10–30 % of individuals. Iron is usually sequestered in complexes with iron-binding proteins such as transferrin, lactoferrin and haemoglobin (Otto et al, 1992). Meningococci encode several surface receptors to strip and acquire iron or haem from these iron-binding proteins, including two TonBdependent haem acquisition systems, HpuAB and HmbR (Perkins-Balding et al, 2004). HmbR is an 89 kDa transmembrane protein that binds haemoglobin (Perkins-Balding et al, 2003). This redundancy in haemoglobin binding receptors may enable meningococci to acquire haem from a variety of sources and niches or may facilitate immune evasion
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
