Abstract
The paradoxical response of Streptococcus sanguinis to drugs prescribed for dental and clinical practices has complicated treatment guidelines and raised the need for further investigation. We conducted a high throughput study on concomitant transcriptome and proteome dynamics in a time course to assess S. sanguinis behaviour under a sub-inhibitory concentration of ampicillin. Temporal changes at the transcriptome and proteome level were monitored to cover essential genes and proteins over a physiological map of intricate pathways. Our findings revealed that translation was the functional category in S. sanguinis that was most enriched in essential proteins. Moreover, essential proteins in this category demonstrated the greatest conservation across 2774 bacterial proteomes, in comparison to other essential functional categories like cell wall biosynthesis and energy production. In comparison to non-essential proteins, essential proteins were less likely to contain ‘degradation-prone’ amino acids at their N-terminal position, suggesting a longer half-life. Despite the ampicillin-induced stress, the transcriptional up-regulation of amino acid-tRNA synthetases and proteomic elevation of amino acid biosynthesis enzymes favoured the enriched components of essential proteins revealing ‘proteomic signatures’ that can be used to bridge the genotype–phenotype gap of S. sanguinis under ampicillin stress. Furthermore, we identified a significant correlation between the levels of mRNA and protein for essential genes and detected essential protein-enriched pathways differentially regulated through a persistent stress response pattern at late time points. We propose that the current findings will help characterize a bacterial model to study the dynamics of essential genes and proteins under clinically relevant stress conditions.
Highlights
Streptococcus sanguinis SK36 is a Gram-positive, facultative anaerobic bacterium that is described as a Janus-faced micro-organism
Based on GenBank clusters of orthologous groups’ (COG) functional categories, we found that S. sanguinis essential genes are unevenly distributed in functional categories (Table 1), biased towards translation (33.2 % of total essential genes), replication and repair (10.7 %), lipid metabolism (9 %) and cell wall/membrane/envelope biogenesis (7.6 %)
With 203 (COG category: R) and 184 (COG category: S) nonessential genes defined as hypothetical genes, the functional category most enriched with non-essential genes is ‘General functional prediction only’ (11.7 % of non-essential genes)
Summary
Streptococcus sanguinis SK36 is a Gram-positive, facultative anaerobic bacterium that is described as a Janus-faced micro-organism. It is an oral commensal that competes with pathogenic bacteria for colonization of the oral cavity [1] through the production of bactericidal hydrogen peroxide that has been shown to eliminate an etiologic agent of dental caries, namely Streptococcus mutans [2]. S. sanguinis has been related to the formation of biofilms in the oral cavity, called dental plaque [3, 4], and has been defined as an opportunistic pathogen that is among the leading etiologic agents of infective endocarditis in patients with heart valve defects [5, 6] and bacteremia in neutropenic patients [7]. Ampicillin and amoxicillin are b-lactam antibiotics that differ only in one hydroxyl group but share the same spectrum of activity against Gram-positive bacteria, despite
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