Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
mBio. 2012 Jul 31;3(4):e00171-12. doi: 10.1128/mBio.00171-12. Print 2012.
Bioavailable levels of trace metals, such as iron and zinc, for bacterial growth in nature are sufficiently low that most microbes have evolved high-affinity binding and transport systems. The microbe Campylobacter jejuni lives in the gastrointestinal tract of chickens, the principal source of human infection. A high-affinity ABC transporter for zinc uptake is required for Campylobacter survival in chicken intestines in the presence of a normal microbiota but not when chickens are raised with a limited microbiota. Mass spectrometric analysis of cecal contents revealed the presence of numerous zinc-binding proteins in conventional chicks compared to the number in limited-microbiota chicks. The presence of a microbiota results in the production of host zinc-binding enzymes, causing a growth restriction for bacteria that lack the high-affinity zinc transporter. Such transporters in a wide range of pathogenic bacteria make them good targets for the development of broad-spectrum antimicrobials.
Zinc is an essential trace element for the growth of most organisms. Quantities of zinc inside cells are highly regulated, as too little zinc does not support growth, while too much zinc is toxic. Numerous bacterial cells require zinc uptake systems for growth and virulence. The work presented here demonstrates that the microbiota in the gastrointestinal tract reduces the quantity of zinc. Without a high-affinity zinc transporter, Campylobacter jejuni, a commensal organism of chickens, is unable to replicate or colonize the gastrointestinal tract. This is the first demonstration of zinc competition between microbiota in the gastrointestinal tract of a host. These results could have profound implications in the field of microbial pathogenesis and in our understanding of host metabolism and the microbiota.
对于细菌在自然界中的生长，痕量金属（如铁和锌）的生物利用度非常低，以至于大多数微生物已经进化出高亲和力的结合和运输系统。弯曲杆菌在鸡的胃肠道中生存，是人类感染的主要来源。对于弯曲杆菌在正常微生物群存在的情况下在鸡肠道中的生存，需要一种高亲和力的 ABC 转运蛋白来摄取锌，但当鸡在有限的微生物群中生长时，则不需要。对盲肠内容物的质谱分析显示，与有限微生物群雏鸡相比，常规雏鸡中存在大量的锌结合蛋白。微生物群的存在导致宿主锌结合酶的产生，从而导致缺乏高亲和力锌转运蛋白的细菌生长受限。广泛存在于各种病原菌中的此类转运蛋白使其成为广谱抗菌药物开发的良好靶标。
锌是大多数生物体生长所必需的痕量元素。细胞内锌的数量受到高度调节，因为锌含量太少不利于生长，而锌含量太多则有毒。许多细菌细胞需要锌摄取系统来生长和毒力。这里介绍的工作表明，胃肠道中的微生物群会减少锌的含量。没有高亲和力的锌转运蛋白，鸡的共生菌弯曲杆菌就无法复制或定殖胃肠道。这是首次证明宿主胃肠道微生物群之间存在锌竞争。这些结果可能对微生物发病机制领域以及我们对宿主代谢和微生物群的理解产生深远影响。
