Unravelling the biology of macrophage infection by gene expression profiling of intracellular <i>Salmonella enterica</i>

TLDR

Intracellular pathogens such as Salmonella must adapt to the phagocytic cell environment, a transition that involves global changes in bacterial gene expression yet whose precise events remain poorly defined. This study reports the complete transcriptional profile of intracellular Salmonella enterica serovar Typhimurium following macrophage infection. The authors profiled the transcriptome of Salmonella Typhimurium inside macrophages to capture these gene expression changes. During replication in J774‑A.1 macrophage‑like cells, 919 of 4451 genes were differentially expressed, showing that intracellular Salmonella is not starved for amino acids or iron, adapts to low phosphate and magnesium but high potassium, uses the Entner–Doudoroff pathway for gluconate, and that nearly half of the regulated genes are of unknown function, constituting the first comprehensive in‑vivo transcriptional map of a bacterial pathogen in mammalian cells.

Abstract

Summary For intracellular pathogens such as Salmonellae , Mycobacteriae and Brucellae , infection requires adaptation to the intracellular environment of the phagocytic cell . The transition from extracellular to intravacuolar environment has been expected to involve a global modulation of bacterial gene expression, but the precise events have been difficult to determine. We now report the complete transcriptional profile of intracellular Salmonella enterica sv. Typhimurium following macrophage infection. During replication in murine macrophage‐like J774‐A.1 cells, 919 of 4451 S. Typhimurium genes showed significant changes in transcription. The expression profile identified alterations in numerous virulence and SOS response genes and revealed unexpected findings concerning the biology of the Salmonella –macrophage interaction. We observed that intracellular Salmonella are not starved for amino acids or iron (Fe 2+ ), and that the intravacuolar environment is low in phosphate and magnesium but high in potassium. S. Typhimurium appears to be using the Entner–Douderoff pathway to use gluconate and related sugars as a carbon source within macrophages. Almost half the in vivo ‐regulated genes were of unknown function, suggesting that intracellular growth involves novel macrophage‐associated functions . This is the first report that identifies the whole set of in vivo‐ regulated genes for any bacterial pathogen during infection of mammalian cells .