Despite being considered the simplest form of life, bacteria remain enigmatic, particularly in light of pathogenesis and evolving antimicrobial resistance. After three decades of genomics, we remain some way from understanding these organisms, and a substantial proportion of genes remain functionally unknown. Methodological advances, principally mass spectrometry (MS), are paving the way for parallel analysis of the proteome, metabolome and lipidome. Each provides a global, complementary assay, in addition to genomics, and the ability to better comprehend how pathogens respond to changes in their internal (e.g. mutation) and external environments consistent with infection-like conditions. Such responses include accessing necessary nutrients for survival in a hostile environment where co-colonizing bacteria and normal flora are acclimated to the prevailing conditions. Multi-omics can be harnessed across temporal and spatial (sub-cellular) dimensions to understand adaptation at the molecular level. Gene deletion libraries, in conjunction with large-scale approaches and evolving bioinformatics integration, will greatly facilitate next-generation vaccines and antimicrobial interventions by highlighting novel targets and pathogen-specific pathways. MS is also central in phenotypic characterization of surface biomolecules such as lipid A, as well as aiding in the determination of protein interactions and complexes. There is increasing evidence that bacteria are capable of widespread post-translational modification, including phosphorylation, glycosylation and acetylation; with each contributing to virulence. This review focuses on the bacterial genotype to phenotype transition and surveys the recent literature showing how the genome can be validated at the proteome, metabolome and lipidome levels to provide an integrated view of organism response to host conditions.
Long Terminal Repeat (LTR) retrotransposons replicate through “copy and paste” mechanisms mediated by reverse transcription in virus-like particles (VLPs) and integration in the nucleus (see article from Lee and Martienssen, pp. 2241–2251). VLP DNA-sequencing reveals complementary DNA (cDNA) replication intermediates from active retrotransposons. Instead of functional linear intermediates that integrate in the nucleus, the Arabidopsis retroelement SISYPHUS lacks features important for nuclear import, and instead accumulates circular cDNA from futile autointegration within the VLP. In Greek mythology, Sisyphus was condemned to the futile task of rolling a huge boulder uphill eternally. Image created and provided Seung Cho Lee, Evan Ernst, and Robert A. Martienssen.
Integrated mass spectrometry-based multi-omics for elucidating mechanisms of bacterial virulence
Lok Man, William P. Klare, Ashleigh L. Dale, Joel A. Cain, Stuart J. Cordwell; Integrated mass spectrometry-based multi-omics for elucidating mechanisms of bacterial virulence. Biochem Soc Trans 1 November 2021; 49 (5): 1905–1926. doi: https://doi.org/10.1042/BST20191088
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