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Characterization of MurNAc kinase in T. forsythia

Tannerella forsythia are anaerobic, Gram-negative bacteria found in periodontal disease-associated biofilms. This oral pathogen is auxotrophic for N-acetylmuramic acid (MurNAc), an important constituent of peptidoglycan (PGN) in bacterial cell wall. Loss of MurNAc leads to impaired cell wall metabolism, leading to growth abrogation and abnormal fusiform morphology. Along with Porphyromonas gingivalis and Treponema denticola, T. forsythia form oral biofilms called ‘red complex’, which are found in severe stages of perionditis and can lead to the loss of tooth if left untreated. 

Genomic analyses of T. forsythia demonstrate lack of genes required for PGN biosynthesis. The intake of MurNAc is mediated by phosphotransferase transporters (PTS) in some bacteria. However, these transporters are not found in T. forsythia and instead, MurNAc intake was mediated by a PTS-independent transporter system that belongs to the sodium symporter superfamily. The gene encoding for this transporter is found within the Tf_murTKQ operon, along with genes encoding for MurNAc-6-phosphate etherase (Tf_MurQ) and a putative sugar kinase (Tf_MurK). 

Biochemical characterization of Tf_MurK revealed high substrate specificity for MurNAc (from Carbosynth) over N-acetylglucosamine (GlcNAc) for phosphorylation (kcat/KM values of 52550 and 0.86 s-1 M-1, respectively). Tf_MurK-deleted mutants presented with accumulation of MurNAc, demonstrating their intact ability to transport but inability to catabolize MurNAC. Nevertheless, these mutants survive, suggesting the utilization of MurNAc for PGN biosynthesis required for cell wall synthesis. Moreover, these mutants survive better in MurNAc-depleted media, due to the diversion from MurNAc catabolism to PGN biosynthesis. Investigating the mechanism of directing MurNAc towards PGN biosynthesis will aid in characterizing MurNAc as a candidate for targeting T. forsythia-mediated periodontal diseases.

For further details, please see the original paper: Hottmann et al (2018)

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