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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): 1521-30 PMID26548613show 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 cross-linking/mass spectrometry approach, we identified interspecies protein-protein interactions in human lung epithelial cells infected with Acinetobacter baumannii. These efforts resulted in identification of 3076 total cross-linked peptide pairs and 46 interspecies protein-protein interactions. Most notably, the key A. baumannii virulence factor, OmpA, was identified cross-linked 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.