Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA.
BMC Microbiol. 2010 Nov 12;10:286. doi: 10.1186/1471-2180-10-286.
Although non-typeable (NT) Haemophilus influenzae and Haemophilus haemolyticus are closely related human commensals, H. haemolyticus is non-pathogenic while NT H. influenzae is an important cause of respiratory tract infections. Phase-variable phosphorylcholine (ChoP) modification of lipooligosaccharide (LOS) is a NT H. influenzae virulence factor that, paradoxically, may also promote complement activation by binding C-reactive protein (CRP). CRP is known to bind more to ChoP positioned distally than proximally in LOS, and the position of ChoP within LOS is dictated by specific licD alleles (designated here as licDI, licDIII, and licDIV) that are present in a lic1 locus. The lic1 locus contains the licA-licD genes, and ChoP-host interactions may also be influenced by a second lic1 locus that allows for dual ChoP substitutions in the same strain, or by the number of licA gene tetranucleotide repeats (5'-CAAT-3') that reflect phase-variation mutation rates.
Using dot-blot hybridization, 92% of 88 NT H. influenzae and 42.6% of 109 H. haemolyticus strains possessed a lic1 locus. Eight percent of NT H. influenzae and none of the H. haemolyticus strains possessed dual copies of lic1. The licDIII and licDIV gene alleles were distributed similarly (18-22%) among the NT H. influenzae and H. haemolyticus strains while licDI alleles were present in 45.5% of NT H. influenzae but in less than 1% of H. haemolyticus strains (P < .0001). NT H. influenzae had an average of 26.8 tetranucleotide repeats in licA compared to 14.8 repeats in H. haemolyticus (P < .05). In addition, NT H. influenzae strains that possessed a licDIII allele had increased numbers of repeats compared to NT H. influenzae with other licD alleles (P < .05).
These data demonstrate that genetic similarities and differences of ChoP expression exist between NT H. influenzae and H. haemolyticus and strengthen the hypothesis that, at the population level, these differences may, in part, provide an advantage in the virulence of NT H. influenzae.
虽然非分型（NT）流感嗜血杆菌和溶血性嗜血杆菌是密切相关的人类共生菌，但溶血性嗜血杆菌是无致病性的，而 NT 流感嗜血杆菌是呼吸道感染的重要原因。脂寡糖（LOS）的阶段可变磷酰胆碱（ChoP）修饰是 NT 流感嗜血杆菌的一种毒力因子，但具有讽刺意味的是，它也可以通过与 C 反应蛋白（CRP）结合来促进补体激活。已知 CRP 与 LOS 中 ChoP 位置较远的位置结合多于位置较近的位置，并且 LOS 中 ChoP 的位置由特定的 licD 等位基因（在此指定为 licDI、licDIII 和 licDIV）决定，这些等位基因存在于 lic1 基因座中。lic1 基因座包含 licA-licD 基因，ChoP-宿主相互作用也可能受到第二个 lic1 基因座的影响，该基因座允许在同一菌株中进行双重 ChoP 取代，或者受 5'-CAAT-3'的 licA 基因四核苷酸重复数（反映阶段变异突变率）的影响。
使用斑点杂交，88%的 88 株 NT 流感嗜血杆菌和 42.6%的 109 株溶血性嗜血杆菌菌株具有 lic1 基因座。8%的 NT 流感嗜血杆菌和无一株溶血性嗜血杆菌菌株具有双重 lic1 拷贝。NT 流感嗜血杆菌和溶血性嗜血杆菌菌株中 licDIII 和 licDIV 基因等位基因的分布相似（分别为 18-22%），而 licDI 等位基因存在于 45.5%的 NT 流感嗜血杆菌中，但存在于不到 1%的溶血性嗜血杆菌中（P <.0001）。NT 流感嗜血杆菌 licA 中的四核苷酸重复数平均为 26.8，而溶血性嗜血杆菌中的重复数为 14.8（P <.05）。此外，具有 licDIII 等位基因的 NT 流感嗜血杆菌菌株的重复次数比具有其他 licD 等位基因的 NT 流感嗜血杆菌菌株多（P <.05）。
这些数据表明，NT 流感嗜血杆菌和溶血性嗜血杆菌之间存在 ChoP 表达的遗传相似性和差异，并加强了这样一种假设，即在群体水平上，这些差异可能部分为 NT 流感嗜血杆菌的毒力提供了优势。
