Antibiotics halt the growth of bacteria by targeting core, essential physiology that is required for life on standard microbiological media. Many more biochemical and virulence processes, however, are required for bacteria to cause infection in a host. Indeed, chemical inhibitors of the latter processes are overlooked using conventional antibiotic drug discovery approaches. Here, we use human blood serum as an alternative growth medium to explore new targets and compounds. High-throughput screening of genetic and chemical libraries identified compounds targeting biological activities required by Klebsiella pneumoniae to grow in serum, such as nucleobase biosynthesis and iron acquisition, and showed that serum can chemically transform compounds to reveal cryptic antibacterial activity. One of these compounds, ruthenium red, was effective in a rat bloodstream infection model. Our data demonstrate that human serum is an effective tool to find new chemical matter to address the current antibiotic resistance crisis.

抗生素通过靶向标准微生物培养基上生命所必需的核心，必不可少的生理学来阻止细菌的生长。然而，细菌引起宿主感染需要更多的生化和毒力过程。实际上，使用常规抗生素药物发现方法忽略了后一种过程的化学抑制剂。在这里，我们使用人血清作为替代生长培养基来探索新的靶标和化合物。遗传和化学文库的高通量筛选鉴定出针对肺炎克雷伯菌所需生物活性的化合物可以在血清中生长，例如核碱基的生物合成和铁的获取，并表明血清可以化学转化化合物以显示出隐秘的抗菌活性。这些化合物之一钌红在大鼠血液感染模型中有效。我们的数据表明，人血清是寻找新的化学物质解决当前抗生素耐药性危机的有效工具。