Discovery of an alternative pathway of peptidoglycan biosynthesis: A new target for pathway specific inhibitors

Abstract

Peptidoglycan in bacterial cell walls is a biopolymer consisting of sugars and amino acids and plays important role in maintaining cell integrity from the environment. Its biosynthesis is a major target for antibiotics and the genes and enzymes involved in the biosynthetic pathway have been well studied. However, we recently identified an alternative pathway in the early stage of peptidoglycan biosynthesis in Xanthomonas oryzae, a plant pathogen causing bacterial blight disease of rice. The distribution of the alternative pathway is limited to relatively few bacterial genera that contain many pathogenic species, including Xylella and Stenotrophomonas, besides Xanthomonas. Thus, the alternative pathway is an attractive target for the development of narrow spectrum antibiotics specific to pathogens. In this minireview, we summarize the discovery of the alternative pathway and identification of its specific inhibitors.

Gastrointestinal tract microbial community of Babylonia areolata and its diversity are closely correlated with the outbreak of disease

“…Our result showed the differences of GI microbial diversity between group D and group H brought about changes in metabolic functions of GI microbiota. According to the results of predicting metabolic functions based on KEGG level2, we found that physiological activity associated with cell growth and death, replication and repair, infectious diseases, signal transduction, cell motility in GI microbiota of group D were stronger or more prominent than those in group H. Accordingly, starch and sucrose metabolism, peptidoglycan biosynthesis, two‐component system, flagellar assembly in group D were stronger or more prominent than those in group H. On the contrary, some normal physiological metabolism, such as lipid metabolism, energy metabolism and amino acid metabolism, happens more often in GI microbiota of group H. These observations indicate that more microorganisms in group D could participate in abnormal physiological activity such as infection, since cell growth and death (Carlson et al, 2015; Wiman & Zhivotovsky, 2017), peptidoglycan biosynthesis (Mirelman & Nuchamowitz, 1979; Ogasawara & Dairi, 2021; Veyron Churlet et al, 2020), two‐component system (Breland et al, 2017; Goodman et al, 2009) and flagellar assembly (Vedantam et al, 2016; Zhang et al, 2012) are direct correlation with disease or infection.…”

Structural Insights into the Penicillin-Binding Protein 4 (DacB) from Mycobacterium tuberculosis

“…By covalently binding to the active site serine of MtbPBP4, β-lactam antibiotics disrupt cell wall synthesis, leading to defects in the peptidoglycan structure and, eventually, bacterial cell lysis. This inhibition of cell wall assembly contributes to the anti-bacterial effects of β-lactam antibiotics against M. tuberculosis [22,24].…”