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2015 ; 22
(11
): 1521-1530
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Host-Microbe Protein Interactions during Bacterial Infection
#MMPMID26548613
Schweppe DK
; Harding C
; Chavez JD
; Wu X
; Ramage E
; Singh PK
; Manoil C
; Bruce JE
Chem Biol
2015[Nov]; 22
(11
): 1521-1530
PMID26548613
show ga
Interspecies protein-protein interactions are essential mediators of infection.
While bacterial proteins required for host cell invasion and infection can be
identified through bacterial mutant library screens, information about host
target proteins and interspecies complex structures has been more difficult to
acquire. Using an unbiased chemical crosslinking/mass spectrometry approach, we
identified interspecies protein-protein interactions in human lung epithelial
cells infected with Acinetobacter baumannii. These efforts resulted in
identification of 3,076 crosslinked peptide pairs and 46 interspecies
protein-protein interactions. Most notably, the key A. baumannii virulence
factor, OmpA, was identified as crosslinked to host proteins involved in
desmosomes, specialized structures that mediate host cell-to-cell adhesion.
Co-immunoprecipitation and transposon mutant experiments were used to verify
these interactions and demonstrate relevance for host cell invasion and acute
murine lung infection. These results shed new light on A. baumannii-host protein
interactions and their structural features, and the presented approach is
generally applicable to other systems.