On the Mode of Action of the Tetracycline Antibiotics in Staphylococcus aureus

Investigating the effect of tetracycline on gut microbiome metabolism and microbe-host interactions

“…TET binds to the 30S fraction of the bacterial ribosome, preventing the binding of aminoacyl-tRNA to the A site of the bacterial ribosome and thereby interfere with the supply and connecting of the amino acids forming proteins (Borghi and Palma, 2014;Hasan et al, 1985). In addition to the primary target, TET can also inhibit a few other processes in bacteria, such as cell division and synthesis of nucleic acid, folic acid, and vitamin B12 (Eagle and Saz, 1954;Hash et al, 1964). Furthermore, vitamin K metabolism and cell wall synthesis are also reported as the targets of TET (Hash et al, 1964).…”

“…In addition to the primary target, TET can also inhibit a few other processes in bacteria, such as cell division and synthesis of nucleic acid, folic acid, and vitamin B12 (Eagle and Saz, 1954;Hash et al, 1964). Furthermore, vitamin K metabolism and cell wall synthesis are also reported as the targets of TET (Hash et al, 1964).…”

“…The target sites, resistance capabilities, and uptake mechanisms specific to a bacterium may lead to the difference in their responses towards the same antibiotic. For instance, TET exposure can inhibit the cell wall synthesis of E. coli (Cheng and Snell, 1961); but not, however, in Staphylococcus aureus (Hash et al, 1964). Moreover, B. fragilis and E. coli have shown efficient uptake of TET through outer membrane porin channels (Fayolle et al, 1980;McMurry and Levy, 1978;Schnappinger and Hillen, 1996), Higher and fast enrichment of Bacteroides compared to Firmicutes in the gut microbial community treated with TET further reveals that the genera Bacteroides are more competitive under TET exposure (Jung et al, 2018).…”

“…The higher fold change in the high dose may result due to the higher availability of TET to act on the target sites; however, the low dose still can induce alterations in some metabolites such as aspartic acid and pyroglutamic acid (Figure 4.3a), which emphasize the possible effect of TET intake on gut microbiome metabolism through the consumption of food products containing TET residues. There are a number of other targets of TET, such as fermentation and oxidation process (Hash et al, 1964), cell wall synthesis (Miller, 1969), and vitamin metabolism (Hash et al, 1964), in addition to its primary target of inhibiting the protein synthesis. Therefore, the resulting metabolic changes could be from direct pathway targeting by TET or due to the inhibition of the synthesis of proteins involved in these pathways (Hash et al, 1964).…”

“…There are a number of other targets of TET, such as fermentation and oxidation process (Hash et al, 1964), cell wall synthesis (Miller, 1969), and vitamin metabolism (Hash et al, 1964), in addition to its primary target of inhibiting the protein synthesis. Therefore, the resulting metabolic changes could be from direct pathway targeting by TET or due to the inhibition of the synthesis of proteins involved in these pathways (Hash et al, 1964). Dysregulations in metabolites related to vitamin metabolism, nucleotide, and amino acid biosynthesis have been reported in previous bacterial metabolomics studies, which also include antibiotics with a similar mode of action (Belenky et al, 2015;Zampieri et al, 2017).…”