A Bacterial Pathogen Senses Host Mannose to Coordinate Virulence
Lifan Wei,
Haoxian Qiao,
Brandon Sit,
Kaiyu Yin,
Guanhua Yang,
Ruiqing Ma,
Jiabao Ma,
Chun Yang,
Jun Yao,
Yue Ma,
Jingfan Xiao,
Xiaohong Liu,
Yuanxing Zhang,
Matthew K. Waldor,
Qiyao Wang
Affiliations
Lifan Wei
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Haoxian Qiao
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Brandon Sit
Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Kaiyu Yin
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Guanhua Yang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Ruiqing Ma
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Jiabao Ma
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Chun Yang
State Key Laboratory of Genetic Engineering, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200433, China
Jun Yao
Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China
Yue Ma
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China
Jingfan Xiao
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
Xiaohong Liu
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China
Yuanxing Zhang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China
Matthew K. Waldor
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA
Qiyao Wang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China; Corresponding author
Summary: Bacterial pathogens are thought to activate expression of virulence genes upon detection of host-associated cues, but identification of the nature of such signals has proved difficult. We generated a genome-scale defined transposon mutant library in Edwardsiella piscicida, an important fish pathogen, to quantify the fitness of insertion mutants for intracellular growth in macrophages and in turbot (Scophthalmus maximus). These screens identified EvrA, a transcription activator that induces expression of esrB, a key virulence regulator. EvrA is directly bound and activated by mannose-6-phosphate (man-6P) derived from actively imported mannose. Mutants lacking EvrA or expressing an EvrA unable to bind man-6P were similarly attenuated in turbot. Exogenously added mannose promoted E. piscicida virulence, and high levels of mannose were detected in fish tissue. Together, these observations reveal that binding of a host-derived sugar to a transcription factor can facilitate pathogen sensing of the host environment and trigger virulence programs. : Pathogenic Organism; Microbiology; Fish Culture Subject Areas: Pathogenic Organism, Microbiology, Fish Culture