Proteome Data Improves Protein Function Prediction in the Interactome of Helicobacter pylori

Abstract

Helicobacter pylori is a common pathogen that is estimated to infect half of the human population, causing several diseases such as duodenal ulcer. Despite one of the first pathogens to be sequenced, its proteome remains poorly characterised as about one third of its proteins have no functional annotation. Here, we integrate and analyze known protein interactions with proteomic and genomic data from different sources. We find that proteins with similar abundances tend to interact. Such an observation is accompanied by a trend of interactions to appear between proteins of similar functions, although some show marked cross-talk to others. Protein function prediction with protein interactions is significantly improved when interactions from other bacteria are included in our network, allowing us to obtain putative functions of more than 300 poorly or previously uncharacterized proteins. Proteins that are critical for the topological controllability of the underlying network are significantly enriched with genes that are up-regulated in the spiral compared to the coccoid form of H. pylori. Determining their evolutionary conservation, we present evidence for 80 protein complexes to be identical in composition with their counterparts in E. coli while 85 are partially conserved but 120 complexes are completely absent. Furthermore, we determine network clusters that coincide with related functions gene essentiality, genetic context, cellular localization, and gene expression in different cellular states.

Crystal Structure of Flagellar Export Chaperone FliS in Complex With Flagellin and HP1076 of Helicobacter pylori

“…Interestingly, the expression of hp1076 is RpoN-dependent and its transcription level is found to be up-regulated together with flaB and flgE in a fliK mutant which displayed impaired motility and polyhook structures (Douillard et al, 2009). Recent interactome studies of H. pylori have further identified the binary complex of FliS-HP1076 and thus highlighting the potential functional significance of this heterodimer (Wuchty et al, 2018). Given that HP1076 is uniquely found in epsilon-proteobacteria and adopts a flagellinlike structure, it may play a specific role for the motility adaptation of this microbial species.…”

Biofilm Formation as a Complex Result of Virulence and Adaptive Responses of Helicobacter pylori

“…Apart from the increased level of SpoT, proteomic studies by Wuchta et al [ 77 ] and Loke et al [ 78 ] showed an increase in the production of the following components in spherical H. pylori forms: outer membrane proteins (Omp7 (HopF), Omp8 (HopG), Omp11 (HorE), Omp15 (HopE), and Omp25 (HopI)), transporter proteins/efflux pumps, flagellin A, urease and hydrogenase subunits, proteins regulating the metal ions concentration (e.g., NikR being crucial for urease and hydrogenase activity [ 79 ]), CagE and CagV (stabilizing the T4SS pilus biogenesis [ 80 ]), VacA (related to cytotoxicity and immunosuppression induction [ 81 ]), lipoprotein LPP20 and TNF-α-inducing protein (both contributing to the carcinogenesis promotion [ 82 ]), as well as MreB (influencing the action of urease, hydrogenase, and VacA [ 83 ]).…”

“…This is associated with the lack of a uniform procedure stimulating the transition of H. pylori from spiral to coccoid forms. Some reach teams use stressful conditions, such as nutritional starvation [ 43 ] or exposure to high oxygen concentrations [ 84 ], while others achieve this through a prolonged cultivation [ 77 , 78 ]. However, it cannot be denied that such procedures can independently affect the transcriptome and/or proteome of H. pylori cells.…”

“…During the maturation of the microcolony into biofilm, a high number of morphological transformations occur, which ultimately result in the presence of a large population of coccoid forms of this bacterium [ 70 , 71 ]. This morphotype is associated with an increase in the expression of adhesins, urease, and hydrogenase as well as transporter proteins/efflux pumps [ 75 , 77 , 78 ]. In addition, spherical forms intensively secrete OMVs, which additionally stabilize the biofilm structure, but also participate in the process of genetic recombination and tolerance to environmental stress (e.g., by the presence of numerous degradative enzymes) [ 25 , 104 , 105 ].…”

“…It should be emphasized here that their results largely depend on the knowledge about the function of specific genes and proteins. As can be seen quite easily, even in recent ‘omics’ research on H. pylori , the function of about 1/3rd of the genes or proteins that are defined as being significantly altered in expression is unknown (termed as “hypothetical protein”) [ 21 , 22 , 77 , 78 , 102 ]. It seems, therefore, that the substantial amount of future research on H. pylori should focus on determining their role in the physiology of this pathogen.…”