A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster model

Environmentally ubiquitous bacteria have acquired extensive abilities to adapt to variable environments, bestowing to some of them the potential to become opportunistic pathogens. This may translate into distinct infection modes according to the route of entry. Whereas Pseudomonas aeruginosa is considered to have two major modes of infection, acute by planktonic cells or chronic through the establishment of biofilms, we report here a novel type of infection whereby ingested bacteria escape from the digestive tract and silently colonize tissues as single cells without strongly affecting the lifespan of the Drosophila host. The bacteria appear to be dormant, a feature shared with persister cells that elude the action of antibiotics. They are characterized by distinct bacterial and colony morphologies, cell surface and motility properties. Their virulence program can nevertheless be reactivated spontaneously or upon injury. We also report that an important host defense of invertebrates, melanization, is activated upon escape of the bacteria into the internal milieu. This activation not only promotes the dormancy of the colonizing bacteria but also protects the host to some degree against secondary infections. As P. aeruginosa is a member of the microbiota of a sizable fraction of human populations, these discoveries may become medically relevant.This article has been formally accetpted by Plos Pathogens, the DOI number for it is: 10.1371/journal.ppat.1012252.

广泛存在于环境中的细菌已演化出多样的环境适应能力，这使得其中部分菌株具备了成为机会致病菌的潜力。这一特性会根据入侵途径的不同，演化出各异的感染模式。尽管铜绿假单胞菌（Pseudomonas aeruginosa）被认为存在两种主要感染模式：浮游态细胞介导的急性感染，以及通过生物被膜形成引发的慢性感染，但本研究报道了一种全新的感染类型：被摄入的细菌逃离消化道后，以单细胞形式悄无声息地定植于宿主组织，且不会显著影响果蝇宿主的寿命。这类细菌呈现休眠状态，这一特征与能够逃避抗生素作用的持留菌（persister cells）一致。它们具备独特的细菌形态、菌落形态、细胞表面特性与运动能力。不过，这类细菌的毒力程序可自发激活，或在宿主受到损伤时被触发。本研究同时发现，当细菌侵入宿主内部环境后，无脊椎动物的关键宿主防御机制——黑化反应（melanization）会被激活。这一黑化反应的激活不仅能够维持定植细菌的休眠状态，还可在一定程度上保护宿主抵御继发感染。由于铜绿假单胞菌是相当一部分人类群体微生物组的组成成员，本研究的这些发现具备一定的医学相关性。本文已被《PLOS Pathogens》正式接收，其DOI编号为：10.1371/journal.ppat.1012252。