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Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins.

ABSTRACT: Infection by SARS-CoV-2, the causative agent of COVID-19, is critically connected with host metabolism. Through functional enrichment analysis, the present study aims to evaluate the biological processes involving host proteins interfered by SARS-CoV-2 to verify the potential metabolic impact of the infection. Furthermore, tissue enrichment analyses and differential gene expression of host proteins were applied to understand the interference by SARS-CoV-2 on tissue levels. Results based on functional and tissue-specific enrichment analyses, presented in this study, suggest that SARS-CoV-2, mediated interference on host proteins, can affect the metabolism and catabolism of molecular building blocks and control intracellular mechanisms, including gene expression in metabolism-related organs, to support viral demands. Thus, SARS-CoV-2 can broadly affect the host metabolism and catabolism at tissue and physiological levels contributing to a more severe disease.

SUBMITTER: Lopes LR

PROVIDER: S-EPMC8099703 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins.

Lopes Luciano Rodrigo LR

Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 20210506 3

Infection by SARS-CoV-2, the causative agent of COVID-19, is critically connected with host metabolism. Through functional enrichment analysis, the present study aims to evaluate the biological processes involving host proteins interfered by SARS-CoV-2 to verify the potential metabolic impact of the infection. Furthermore, tissue enrichment analyses and differential gene expression of host proteins were applied to understand the interference by SARS-CoV-2 on tissue levels. Results based on funct ...[more]

PMID: 33956332

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Project description:BackgroundSpace environment imposes a range of challenges to mammalian physiology and the gut microbiota, and interactions between the two are thought to be important in mammalian health in space. While previous findings have demonstrated a change in the gut microbial community structure during spaceflight, specific environmental factors that alter the gut microbiome and the functional relevance of the microbiome changes during spaceflight remain elusive.MethodsWe profiled the microbiome using 16S rRNA gene amplicon sequencing in fecal samples collected from mice after a 37-day spaceflight onboard the International Space Station. We developed an analytical tool, named STARMAPs (Similarity Test for Accordant and Reproducible Microbiome Abundance Patterns), to compare microbiome changes reported here to other relevant datasets. We also integrated the gut microbiome data with the publically available transcriptomic data in the liver of the same animals for a systems-level analysis.ResultsWe report an elevated microbiome alpha diversity and an altered microbial community structure that were associated with spaceflight environment. Using STARMAPs, we found the observed microbiome changes shared similarity with data reported in mice flown in a previous space shuttle mission, suggesting reproducibility of the effects of spaceflight on the gut microbiome. However, such changes were not comparable with those induced by space-type radiation in Earth-based studies. We found spaceflight led to significantly altered taxon abundance in one order, one family, five genera, and six species of microbes. This was accompanied by a change in the inferred microbial gene abundance that suggests an altered capacity in energy metabolism. Finally, we identified host genes whose expression in the liver were concordantly altered with the inferred gut microbial gene content, particularly highlighting a relationship between host genes involved in protein metabolism and microbial genes involved in putrescine degradation.ConclusionsThese observations shed light on the specific environmental factors that contributed to a robust effect on the gut microbiome during spaceflight with important implications for mammalian metabolism. Our findings represent a key step toward a better understanding the role of the gut microbiome in mammalian health during spaceflight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew health during long-term human space expeditions.

Project description:Fungi of the genus Pneumocystis are obligate parasites that colonize mammals' lungs and are host species specific. Pneumocystis jirovecii and Pneumocystis carinii infect, respectively, humans and rats. They can turn into opportunistic pathogens in immunosuppressed hosts, causing severe pneumonia. Their cell cycle is poorly known, mainly because of the absence of an established method of culture in vitro It is thought to include both asexual and sexual phases. Comparative genomic analysis suggested that their mode of sexual reproduction is primary homothallism involving a single mating type (MAT) locus encompassing plus and minus genes (matMc, matMi, and matPi; Almeida et al., mBio 6:e02250-14, 2015). Thus, each strain would be capable of sexual reproduction alone (self-fertility). However, this is a working hypothesis derived from computational analyses that is, in addition, based on the genome sequences of single isolates. Here, we tested this hypothesis in the wet laboratory. The function of the P. jirovecii and P. carinii matMc genes was ascertained by restoration of sporulation in the corresponding mutant of fission yeast. Using PCR, we found the same single MAT locus in all P. jirovecii isolates and showed that all three MAT genes are often concomitantly expressed during pneumonia. Extensive homology searches did not identify other types of MAT transcription factors in the genomes or cis-acting motifs flanking the MAT locus that could have been involved in MAT switching or silencing. Our observations suggest that Pneumocystis sexuality through primary homothallism is obligate within host lungs to complete the cell cycle, i.e., produce asci necessary for airborne transmission to new hosts.IMPORTANCE Fungi of the genus Pneumocystis colonize the lungs of mammals. In immunosuppressed human hosts, Pneumocystis jirovecii may cause severe pneumonia that can be fatal. This disease is one of the most frequent life-threatening invasive fungal infections in humans. The analysis of the genome sequences of these uncultivable pathogens suggested that their sexual reproduction involves a single partner (self-fertilization). Here, we report laboratory experiments that support this hypothesis. The function of the three genes responsible for sexual differentiation was ascertained by the restoration of sexual reproduction in the corresponding mutant of another fungus. As predicted by self-fertilization, all P. jirovecii isolates harbored the same three genes that were often concomitantly expressed within human lungs during infection. Our observations suggest that the sexuality of these pathogens relies on the self-fertility of each isolate and is obligate within host lungs to complete the cell cycle and allow dissemination of the fungus to new hosts.

Dataset Information

Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins.

Publications

Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins.

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