Rasmussen M, Björck L
Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, Lund University, BMC, B14, Tornavägen 10, S-221 84 Lund, Sweden.
Mol Microbiol. 2001 Jun;40(6):1427-38. doi: 10.1046/j.1365-2958.2001.02493.x.
Slipped-strand mispairing at sites containing so-called coding repeats (CRs) can lead to phase variation of surface proteins in Gram-negative bacteria. This mechanism, believed to contribute to virulence, has so far not been identified in a Gram-positive bacterium. In the genome of the Gram-positive human pathogen Streptococcus pyogenes, we identified pentanucleotide CRs within a putative signal sequence of an open reading frame (ORF) encoding a novel collagen-like surface protein, denoted SclB. In 12 S. pyogenes strains, the number of CRs in the sclB gene varied from three to 19, rendering the start codon in frame with the downstream ORF in four strains and out of frame in eight strains. A protein reacting with anti-SclB antibodies could only be solubilized from three strains, all containing an intact sclB gene. Variations in the number of CRs were observed within strains of the same M serotype and occurred during growth of S. pyogenes in fresh human blood, but not in medium. The SclB protein has a hypervariable N-terminal part, a collagen-like central part and a typical cell wall sorting sequence containing the LPXTGX motif. SclB is related to the collagen-like SclA and is, like SclA, involved in the adhesion of S. pyogenes bacteria to human cells. However, the Mga protein, known to upregulate sclA and several additional genes encoding virulence factors of S. pyogenes, downregulates sclB transcription. This observation and the potential of SclB to phase vary by slipped-strand mispairing emphasize the unique regulation of this novel S. pyogenes surface protein.
在含有所谓编码重复序列（CRs）的位点发生的滑链错配可导致革兰氏阴性菌表面蛋白的相变。这种机制被认为与毒力有关，迄今为止在革兰氏阳性菌中尚未发现。在革兰氏阳性人类病原体化脓性链球菌的基因组中，我们在一个编码新型胶原样表面蛋白（称为SclB）的开放阅读框（ORF）的假定信号序列内鉴定出五核苷酸CRs。在12株化脓性链球菌菌株中，sclB基因中的CRs数量从3个到19个不等，使得起始密码子在4株菌株中与下游ORF处于同一阅读框，而在8株菌株中则不在同一阅读框。一种与抗SclB抗体反应的蛋白质只能从3株菌株中溶解出来，这3株菌株均含有完整的sclB基因。在同一M血清型的菌株中观察到CRs数量的变化，并且在化脓性链球菌在新鲜人血中生长时发生，但在培养基中不发生。SclB蛋白具有高度可变的N末端部分、胶原样的中央部分和包含LPXTGX基序的典型细胞壁分选序列。SclB与胶原样的SclA相关，并且与SclA一样，参与化脓性链球菌对人细胞的粘附。然而，已知上调sclA和其他几个编码化脓性链球菌毒力因子的基因的Mga蛋白会下调sclB转录。这一观察结果以及SclB通过滑链错配发生相变的可能性强调了这种新型化脓性链球菌表面蛋白的独特调控。
