Selective and targeted removal of individual species or strains of bacteria from complex communities can be desirable over traditional, broadly acting antibacterials in several contexts. However, generalizable strategies that accomplish this with high specificity have been slow to emerge. Here we develop programmed inhibitor cells (PICs) that direct the potent antibacterial activity of the type VI secretion system (T6SS) against specified target cells. The PICs express surface-displayed nanobodies that mediate antigen-specific cell–cell adhesion to effectively overcome the barrier to T6SS activity in fluid conditions. We demonstrate the capacity of PICs to efficiently deplete low-abundance target bacteria without significant collateral damage to complex microbial communities. The only known requirements for PIC targeting are a Gram-negative cell envelope and a unique cell surface antigen; therefore, this approach should be generalizable to a wide array of bacteria and find application in medical, research, and environmental settings.

在多种情况下，与传统的、作用广泛的抗菌剂相比，从复杂群落中选择性和有针对性地去除单个物种或细菌菌株是可取的。然而，以高特异性实现这一目标的通用策略却迟迟没有出现。在这里，我们开发了程序化抑制细胞 (PICs)，它指导 VI 型分泌系统 (T6SS) 对特定靶细胞的有效抗菌活性。PICs 表达表面展示的纳米抗体，介导抗原特异性细胞 - 细胞粘附，以有效克服流体条件下 T6SS 活性的障碍。我们展示了 PIC 有效消耗低丰度目标细菌而不会对复杂微生物群落造成重大附带损害的能力。PIC 靶向的唯一已知要求是革兰氏阴性细胞包膜和独特的细胞表面抗原；因此，这种方法应该可以推广到广泛的细菌，并在医学、研究和环境环境中得到应用。