Proteomic Profiling during Infection Distinguishes the Intracellular Environment of Host Cells.

Authors:
Yanhua Liu
Yanhua Liu
Shenyang Pharmaceutical University
China
Jiaqi Fu
Jiaqi Fu
Institute of Environmental Health Sciences
United States
Sen Cheng
Sen Cheng
Ruhr-University Bochum
Germany
Mei Wu
Mei Wu
Wellman Center for Photomedicine
Boston | United States
Dr. Zhen Wang, MD,PhD
Dr. Zhen Wang, MD,PhD
Shanghai Tenth People’s Hospital, Tongji University School of Medicine
Professor
Nephrology
Shanghai | China

mSystems 2019 Mar-Apr;4(2). Epub 2019 Apr 9.

Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, People's Republic of China.

Essential to bacterial pathogenesis, Salmonella enterica serovar Typhimurium ( Typhimurium) has evolved the capacity to quickly sense and adapt to specific intracellular environment within distinct host cells. Here we examined Typhimurium proteomic remodeling within macrophages, allowing direct comparison with our previous studies in epithelial cells. In addition to many shared features, our data revealed proteomic signatures highly specific to one type of host cells. Notably, intracellular Typhimurium differentially regulates the two type III secretion systems (T3SSs) far more quickly in macrophages than in epithelial cells; bacterial flagellar and chemotaxis systems degenerate more quickly in macrophages than in HeLa cells as well. Importantly, our comparative analysis uncovered high levels of induction of bacterial histidine biosynthesis in macrophages but not in epithelial cells. Targeted metabolomic measurements revealed markedly lower histidine levels within macrophages. Intriguingly, further functional studies established that histidine biosynthesis that is defective (due to a mutation) renders the bacterium (strain SL1344) hypersensitive to intracellular shortage of this amino acid. Indeed, another Typhimurium strain, namely, strain 14028s, with a fully functional biosynthetic pathway exhibited only minor induction of the operon within infected macrophages. Our work thus provided novel insights into Typhimurium adaptation mechanisms within distinct host cells and also provided an elegant paradigm where proteomic profiling of intracellular pathogens is utilized to discriminate specific host environments (e.g., on the basis of nutrient availability). Typhimurium is one of the leading causes of foodborne bacterial infection. Nevertheless, how adapts to distinct types of host cells during infection remains poorly understood. By contrasting intracellular proteomes from both infected macrophages and epithelial cells, we found striking proteomic signatures specific to particular types of host cells. Notably, proteomic remodeling exhibited quicker kinetics in macrophages than in epithelial cells with respect to bacterial virulence and flagellar and chemotaxis systems. Furthermore, we unveiled high levels of induction of bacterial histidine biosynthesis in macrophages but not in epithelial cells, which is attributable to differing intracellular levels of this amino acid. Intriguingly, we found that a defective gene renders a strain hypersensitive to histidine shortage in macrophages. Overall, our work reveals specific adaptation mechanisms in distinct host cells, which should aid in the development of novel anti-infection strategies.

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.00314-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456673PMC
April 2019
1 Read

Publication Analysis

Top Keywords

host cells
28
epithelial cells
24
macrophages epithelial
20
cells
14
histidine biosynthesis
12
distinct host
12
macrophages
10
cells notably
8
mechanisms distinct
8
high levels
8
adaptation mechanisms
8
types host
8
macrophages work
8
infected macrophages
8
proteomic profiling
8
amino acid
8
levels induction
8
intracellular environment
8
flagellar chemotaxis
8
biosynthesis macrophages
8

Similar Publications