Richardson A R, Stojiljkovic I
Department of Microbiology and Immunology, Emory University School of Medicine, 3001 Rollins Research Center, Atlanta, Georgia 30322, USA.
J Bacteriol. 1999 Apr;181(7):2067-74. doi: 10.1128/JB.181.7.2067-2074.1999.
Neisseria meningitidis uses hemoglobin (Hb) as an iron source via two TonB-dependent outer membrane receptors, HmbR and HpuB. Analysis of 25 epidemiologically unrelated clinical isolates from serogroups A, B, C, and Y revealed that 64% strains possessed both Hb receptor genes. Examination of the hmbR expression pattern in strains in which the hpuB gene was genetically inactivated revealed two distinct Hb utilization phenotypes. Five strains retained the ability to grow as a confluent lawn, while seven grew only as single colonies around Hb discs. The single-colony phenotype observed for some hpuB mutants is suggestive of phase variation of hmbR. The length of the poly(G) tract starting at position +1164 of hmbR absolutely correlated with the two Hb utilization phenotypes. All five strains that grew as confluent lawns around Hb discs possessed either 9 or 12 consecutive G residues. All seven strains that grew as single colonies around Hb discs had poly(G) tracts of a length other than 9 or 12. These single-colony variants that arose around the Hb discs had poly(G) tracts with either 9 or 12 consecutive G residues restoring the hmbR reading frame. Inactivation of hmbR in these strains resulted in a loss of Hb utilization, demonstrating that the change in the hmbR gene was responsible for the phenotypic switch. The switching rates from hmbR phase off to phase on were approximately 5 x 10(-4) in four serogroup C strains, 2 x 10(-2) in the serogroup A isolate, and 7 x 10(-6) in the serogroup B isolate.
脑膜炎奈瑟菌通过两种依赖TonB的外膜受体HmbR和HpuB利用血红蛋白（Hb）作为铁源。对来自A、B、C和Y血清群的25株流行病学无关的临床分离株进行分析，发现64%的菌株同时拥有两种Hb受体基因。对hpuB基因被基因敲除的菌株中hmbR表达模式的检测揭示了两种不同的Hb利用表型。五株菌株保留了形成汇合菌苔生长的能力，而七株仅在Hb圆盘周围以单个菌落形式生长。一些hpuB突变体观察到的单菌落表型提示hmbR存在相变。从hmbR第+1164位开始的聚（G）序列长度与两种Hb利用表型完全相关。所有在Hb圆盘周围形成汇合菌苔生长的五株菌株都拥有9个或12个连续的G残基。所有在Hb圆盘周围以单个菌落形式生长的七株菌株的聚（G）序列长度不是9个或12个。这些在Hb圆盘周围出现的单菌落变体具有9个或12个连续G残基的聚（G）序列，恢复了hmbR的阅读框。在这些菌株中敲除hmbR导致Hb利用丧失，表明hmbR基因的变化是表型转换的原因。在四株C血清群菌株中，hmbR从关闭状态到开启状态的转换率约为5×10⁻⁴，在A血清群分离株中为2×10⁻²，在B血清群分离株中为7×10⁻⁶。
