Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2

We have previously described HpuAB, a two-component receptor that mediates binding to haemoglobin (Hb), haemoglobin-haptoglobin (Hb-Hp) and apo-haptog lobin (Hp). In this communication, we constructed non-polar mutations in th e hpuA and hpuB loci to examine the individual roles of HpuA and HpuB. Our results indicate that both HpuA and HpuB are required for the acquisition o f Fe from Hb and Hb-Hp. We isolated Hb utilization-positive (Hbf) variants of our Hb utilization-negative (Hb-) hpu mutants at a frequency of 10(-3) a nd demonstrated that the Hb+ phenotype resulted from the expression of a se cond Hb receptor, HmbR. Expression of HmbR in DNM2 was found to be controll ed by translational frameshifting involving a polyguanine (G) tract located within the hmbR locus. The hpuA locus also contains a poly(G) tract, which suggested that meningococci could phase vary each Hb receptor independentl y by slip-strand mispairing in the poly(G) tracts found in hpuA and hmbR. T hus, we isolated a naturally occurring Hb- variant of DNM2, designated DNM2 Hb-, which did not express either HpuAB or HmbR. Hb+ variants of DNM2Hb- w ere selected and examined for HpuAB and HmbR expression. In each instance, acquisition of HpuAB or HmbR expression was correlated with phase variation in the poly(G) tract of each Hb receptor.