The human pathogen Pseudomonas aeruginosa harbors three paralogous zinc proteases annotated as AmpD, AmpDh2, and AmpDh3, which turn over the cell wall and cell wall‐derived muropeptides. AmpD is cytoplasmic and plays a role in the recycling of cell wall muropeptides, with a link to antibiotic resistance. AmpDh2 is a periplasmic soluble enzyme with the former anchored to the inner leaflet of the outer membrane. We document, herein, that the type VI secretion system locus II (H2‐T6SS) of P. aeruginosa delivers AmpDh3 (but not AmpD or AmpDh2) to the periplasm of a prey bacterium upon contact. AmpDh3 hydrolyzes the cell wall peptidoglycan of the prey bacterium, which leads to its killing, thereby providing a growth advantage for P. aeruginosa in bacterial competition. We also document that the periplasmic protein PA0808, heretofore of unknown function, affords self‐protection from lysis by AmpDh3. Cognates of the AmpDh3‐PA0808 pair are widely distributed across Gram‐negative bacteria. Taken together, these findings underscore the importance of their function as an evolutionary advantage and that of the H2‐T6SS as the means for the manifestation of the effect.

中文翻译：

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VI 型分泌系统提供细胞壁酰胺酶以靶向细菌竞争者。

人类病原体铜绿假单胞菌含有三种旁系同源锌蛋白酶，注释为 AmpD、AmpDh2 和 AmpDh3，它们可以翻转细胞壁和细胞壁衍生的多肽。AmpD 是细胞质的，在细胞壁多肽的再循环中发挥作用，与抗生素耐药性有关。AmpDh2 是一种周质可溶性酶，前者固定在外膜的内小叶上。我们在本文中记录了铜绿假单胞菌的VI 型分泌系统位点 II (H2-T6SS)在接触时将 AmpDh3（但不是 AmpD 或 AmpDh2）递送至猎物细菌的周质。AmpDh3 水解猎物细菌的细胞壁肽聚糖，导致其被杀死，从而为铜绿假单胞菌提供生长优势在细菌竞争中。我们还证明，迄今为止功能未知的周质蛋白 PA0808 提供自我保护，免受 AmpDh3 裂解。AmpDh3-PA0808 对的同源物广泛分布于革兰氏阴性菌中。总之，这些发现强调了它们作为进化优势的功能的重要性，以及 H2-T6SS 作为效果表现手段的重要性。