Gemmell C G, Peterson P K, Schmeling D, Kim Y, Mathews J, Wannamaker L, Quie P G
J Clin Invest. 1981 May;67(5):1249-56. doi: 10.1172/jci110152.
Streptococcus pyogenes, bearing M-protein on its surface, resists opsonization by normal human serum and subsequent phagocytosis by human polymorphonuclear leukocytes. Previous studies have shown that M-protein positive organisms are poorly opsonized by the alternate pathway of complement. In an attempt to define further the role of the surface components of S. pyogenes in this process, we examined the ability of clindamycin, an antibiotic that inhibits protein biosynthesis, to alter bacterial opsonization. An M-protein positive strain of S. pyogenes was grown in varying concentrations of clindamycin at levels lower than those which inhibited growth, i.e., at levels less than the minimal inhibitory concentration. These bacteria were incubated with purified human polymorphonuclear leukocytes and peripheral blood monocytes. Significant enhancement of bacterial opsonization, phagocytosis, and killing resulted. Measurement of complement consumption and binding of the third component of complement (C3) onto the bacterial surface demonstrated that organisms grown in the presence of clindamycin activated complement more readily and fixed more C3 on their surface. Electron microscopy revealed the probable basis for these findings. Streptococci exposed to clindamycin during growth were largely denuded of surface "fuzz," the hairlike structures bearing M-protein. We conclude that the incorporation of clindamycin at concentrations that fail to inhibit growth of S. pyogenes nevertheless causes significant changes in the capacity of these bacteria to resist opsonization by serum complement. These findings support the hypothesis that M-protein inhibits bacterial opsonization by interfering with effective complement activation on the bacterial surface.
表面带有M蛋白的化脓性链球菌可抵抗正常人血清的调理作用以及随后人类多形核白细胞的吞噬作用。先前的研究表明,M蛋白阳性的微生物很难通过补体替代途径被调理。为了进一步明确化脓性链球菌表面成分在此过程中的作用,我们研究了克林霉素(一种抑制蛋白质生物合成的抗生素)改变细菌调理作用的能力。化脓性链球菌的M蛋白阳性菌株在低于抑制生长浓度(即低于最低抑菌浓度)的不同浓度克林霉素中培养。将这些细菌与纯化的人类多形核白细胞和外周血单核细胞一起孵育。结果细菌的调理作用、吞噬作用和杀伤作用均得到显著增强。补体消耗的测定以及补体第三成分(C3)在细菌表面的结合表明,在克林霉素存在下生长的微生物更容易激活补体,并且在其表面固定更多的C3。电子显微镜揭示了这些发现的可能原因。在生长过程中接触克林霉素的链球菌表面大部分“绒毛”(带有M蛋白的毛发状结构)脱落。我们得出结论,以未能抑制化脓性链球菌生长的浓度加入克林霉素,仍会导致这些细菌抵抗血清补体调理作用的能力发生显著变化。这些发现支持了以下假设:M蛋白通过干扰细菌表面有效的补体激活来抑制细菌的调理作用。