Abstract

The peptidoglycan (PG), as the exoskeleton of most prokaryotes, maintains a defined shape and ensures cell integrity against the high internal turgor pressure. These important roles have attracted researchers to target PG metabolism in order to control bacterial infections. Most studies, however, have been performed in bacteria grown under laboratory conditions, leading to only a partial view on how the PG is synthetized in natural environments. As a case in point, PG metabolism and its regulation remain poorly understood in symbiotic and pathogenic bacteria living inside eukaryotic cells. This review focuses on the PG metabolism of intracellular bacteria, emphasizing the necessity of more in vivo studies involving the analysis of enzymes produced in the intracellular niche and the isolation of PG from bacteria residing within eukaryotic cells. The review also points to persistent infections caused by some intracellular bacterial pathogens and the extent at which the PG could contribute to establish such physiological state. Based on recent evidences, I speculate on the idea that certain structural features of the PG may facilitate attenuation of intracellular growth. Lastly, I discuss recent findings in endosymbionts supporting a cooperation between host and bacterial enzymes to assemble a mature PG.

Highlights

  • The peptidoglycan (PG) is a covalently closed macromolecule that defines bacterial shape and preserves cell integrity by withstanding the high internal osmotic pressure

  • The basic PG structure conserved among all eubacteria consists in a glycan backbone made of repeating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) units linked by β-1,4-glycosidic bonds and cross-linked by short stem peptides (Pazos & Peters, 2019; Typas, Banzhaf, Gross, & Vollmer, 2012; Vollmer, Blanot, & Pedro, 2008)

  • The peptides attached to NAM are pentapeptides with the sequence l-alanine (l-Ala)d-glutamic acid (d-Glu)-dibasic amino acid-d-alanine (d-Ala)-d-Ala

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Summary

| INTRODUCTION

The peptidoglycan (PG) is a covalently closed macromolecule that defines bacterial shape and preserves cell integrity by withstanding the high internal osmotic (turgor) pressure. Unlike other d,d-carboxypeptidases like PBP4, PBP5, PBP6 and PBP7; PBP6b is the only capable of suppressing a cell shape defect at acidic pH (Peters et al, 2016) Another recent study involving complementation of an E. coli PBP5null mutant with other d,d-carboxypeptidases reported divergence in function, concluding that the balanced activity of these d,d-carboxypeptidases is required to ensure synthesis of a robust mature PG (Meiresonne, Ploeg, Hink, & Blaauwen, 2017). This work showed the capacity of this ‘intracellularly-induced PBP’ to drive cell division in mutants lacking PBP3, which is essential in E. coli (Castanheira, Cestero, Garcia-del Portillo, & Pucciarelli, 2018; Castanheira et al, 2017) These latter findings highlight the suitability of working with facultative intracellular bacterial pathogens to uncover new phenomena related to PG plasticity and specialization of PG enzymes

PG enzyme production
Findings
Proteomics and integrative omic approaches for understanding
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