Modulation of Peptidoglycan Synthesis by Recycled Cell Wall Tetrapeptides

Abstract

Highlights d Vibrio cholerae releases peptidoglycan (PG) fragments edited with NCDAAs d Recycling of NCDAA-muropeptides induces the accumulation of PG-tetrapeptide precursors d V. cholerae recycled tetrapeptides are substrates for PG synthesis d Recycled PG-tetrapeptides control cell wall synthesis and crosslinking

A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity

“…The soluble fraction obtained from muramidase digestion was reduced using 0.5 M sodium borate (pH 9.5) and sodium borohydride (10 mg/ml) and the pH was adjusted to 3.5 with phosphoric acid for liquid chromatography (LC). Solubilized muropeptides were detected and analysed by LC-MS using UPLC coupled with a Xevo G2/XS Q-TOF mass spectrometer (Waters Corp.) operated in positive ionization mode 108 . Data were acquired and processed using the UNIFI software package (Waters Corp.).…”

Binding of non-canonical peptidoglycan controls Vibrio cholerae broad spectrum racemase activity

“…This precise molecular fit between the BsrV structure and the two stem peptides radiating from the same strand (separated by one helix turn lends) additionally enforce the idea that BsrV activity may be regulated by its binding to macromolecular peptidoglycan. Furthermore, our data suggest that the extent of such regulation will vary according to the NCDAAs content of the peptidoglycan, and thus inhibition will be maximal during the stationary phase, when NCDAAs incorporation into the cell wall is completed [8] , [10] , [11] .

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“…Negative feedback control of BsrV activity by non-canonically modified-peptidoglycan seems reasonable given that NCDAAs reduce peptidoglycan synthesis [8] , [10] , [11] and that excessive concentration of NCDAAs can be lethal [18] . According to our model, the synthesis of BsrV will be produced on early stationary phase conditions in a RpoS dependent manner [8] .…”

“…In this context, BsrV is expressed, and its activity drives the production and release of millimolar concentrations of NCDAAs to the extracellular media. NCDAAs can then be used as substrates by certain cell wall synthetic enzymes to induce chemical changes in the peptidoglycan composition [8] , [10] , [11] . It has been demonstrated that such cell wall chemical editing by NCDAA down-regulates peptidoglycan synthesis to enable cell wall adaptation to stationary phase conditions [8] , [10] , [11] .…”

“…In addition to being regulators of peptidoglycan synthesis and integrity [8] , [10] , [11] , NCDAA has also been reported to be involved in diverse cellular processes such as catabolism [12] , biofilm formation [13] , bacteria-bacteria interactions [14] , microbiome biodiversity [15] , modulation of host immune cells, and immune cell response [16] . As their L-enantiomeric counterparts, the physiological role of NCDAAs depends both on each particular bacteria and the chemical properties of the NCDAA produced [7] , [17] .…”