Elucidating the network features and evolutionary attributes of intra- and interspecific protein-protein interactions between human and pathogenic bacteria

Abstract

Host-pathogen interaction is one of the most powerful determinants involved in coevolutionary processes covering a broad range of biological phenomena at molecular, cellular, organismal and/or population level. The present study explored host-pathogen interaction from the perspective of human-bacteria protein-protein interaction based on large-scale interspecific and intraspecific interactome data for human and three pathogenic bacterial species, Bacillus anthracis, Francisella tularensis and Yersinia pestis. The network features revealed a preferential enrichment of intraspecific hubs and bottlenecks for both human and bacterial pathogens in the interspecific human-bacteria interaction. Analyses unveiled that these bacterial pathogens interact mostly with human party-hubs that may enable them to affect desired functional modules, leading to pathogenesis. Structural features of pathogen-interacting human proteins indicated an abundance of protein domains, providing opportunities for interspecific domain-domain interactions. Moreover, these interactions do not always occur with high-affinity, as we observed that bacteria-interacting human proteins are rich in protein-disorder content, which correlates positively with the number of interacting pathogen proteins, facilitating low-affinity interspecific interactions. Furthermore, functional analyses of pathogen-interacting human proteins revealed an enrichment in regulation of processes like metabolism, immune system, cellular localization and transport apart from divulging functional competence to bind enzyme/protein, nucleic acids and cell adhesion molecules, necessary for host-microbial cross-talk.

Figure 1

Proportion of pathogen interacting proteins in human hub-bottleneck, hub-nonbottleneck, nonhub-bottleneck and nonhub-nonbottleneck proteins.

Figure 2

Proportion of essential proteins in pathogen-interacting and noninteracting hubs and nonhubs.

Figure 3

Evolutionary rate (dN/dS ratio) of pathogen-interacting and noninteracting human proteins within hubs and nonhubs using 1:1 chimpanzee and mouse orthologs.

Figure 4

Proportion of pathogen-interacting human proteins belonging to different disorder bins.

Figure 5

Mean Interpro protein domains: (A) pathogen noninteracting and interacting human proteins subdivided n number of interacting pathogens for a particular human protein; (B) pathogen interacting and noninteracting human proteins subdivided in hub and nonhub classes.