Dynamic niche-specific adaptations in Neisseria meningitidis during infection.
Neisseria meningitidis is an opportunistic human pathogen that usually colonizes the nasopharyngeal mucosa asymptomatically. Upon invasion into the blood and central nervous system, this bacterium triggers a fulminant inflammatory reaction with the manifestations of septicemia and meningitis, causing high morbidity and mortality. To reveal the bacterial adaptations to specific and dynamic host environments, we performed a comprehensive proteomic survey of N. meningitidis isolated from the nasal mucosa, CSF and blood of a mouse disease model. We could identify 51 proteins whose expression pattern has been changed during infection, many of which have not yet been characterized. The abundance of proteins was markedly lower in the bacteria isolated from the nasal mucosa compared to the bacteria from the blood and CSF, indicating that initiating adhesion is the harshest challenge for meningococci. The high abundance of the glutamate dehydrogenase (GdhA) and Opa1800 proteins in all bacterial isolates suggests their essential role in bacterial survival in vivo. To evaluate the biological relevance of our proteomic findings, four candidate proteins from representative functional groups, such as the bacterial chaperone GroEL, IMP dehydrogenase GuaB, and membrane proteins PilQ and NMC0101, were selected and their impact on bacterial fitness was investigated by mutagenesis assays. This study provides an integrated picture of bacterial niche-specific adaptations during consecutive infection processes.
School of Life Sciences, Inner Mongolia University for Nationalities, Tongliao 028000, China. Electronic address: nmdliuyan@163.com.
Yan
Y
Liu
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Ding
D
Zhang
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Åke
Å
Engström
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Gábor
G
Merényi
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Matthias
M
Hagner
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Hairu
H
Yang
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Asaomi
A
Kuwae
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Yi
Y
Wan
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Mikael
M
Sjölinder
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 106 91, Sweden.
Hong
H
Sjölinder
D000222:Adaptation, Physiological; D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D002353:Carrier State / Q000382:microbiology; D002555:Cerebrospinal Fluid / Q000382:microbiology; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D016920:Meningitis, Bacterial / Q000382:microbiology; D008589:Meningococcal Infections / Q000382:microbiology*; D051379:Mice; D009297:Nasal Mucosa / Q000382:microbiology; D009345:Neisseria meningitidis / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D020543:Proteome / Q000032:analysis; D037521:Virulence Factors / Q000235:genetics
D020543:Proteome; D037521:Virulence Factors
Host adaptation; Neisseria meningitidis; Proteomic analysis; Virulence