Bacterial Peptidoglycan-Degrading Enzymes and Their Impact on Host Muropeptide Detection

University of Colorado, Denver, Colo, USA.
Journal of Innate Immunity (Impact Factor: 4.35). 02/2009; 1(2):88-97. DOI: 10.1159/000181181
Source: PubMed


Peptidoglycan (PGN) is a major component of the bacterial cell envelope in both Gram-positive and Gram-negative bacteria. These muropeptides can be produced or modified by the activity of bacterial glycolytic and peptidolytic enzymes referred to as PGN hydrolases and autolysins. Some of these bacterial enzymes are crucial for bacterial pathogenicity and have been shown to modulate muropeptide release and/or host innate immune responses. The ability of muropeptides to modulate host responses is due to the fact that eukaryotes do not produce PGN and have instead evolved numerous strategies to detect intact PGN and PGN fragments (muropeptides). Here we review the structure of PGN and introduce the various bacterial enzymes known to degrade or modify bacterial PGN. Host factors involved in PGN and muropeptide detection are also briefly discussed, as are examples of how specific bacterial pathogens use PGN degradation and modification to subvert host innate immunity.

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    • "The peptidoglycan hydrolases are important in bacterial pathogenicity [13, 14]. These enzymes modulate muropeptide release which in turn activates host innate immune responses [13]. "
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    International Journal of Microbiology 01/2014; 2014:615965. DOI:10.1155/2014/615965
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    • "Besides this inhibition of the direct bacteriolytic activity of lysozyme , lysozyme inhibitors might also indirectly affect bacteria– host interactions. By binding lysozyme, they possibly influence the release of peptidoglycan fragments, which is known to modulate the immune response and inflammation [16] [17] [18]. Meanwhile, the 3D-structure for a representative of each of the c-type lysozyme inhibitor families (Ivy from E. coli and MliC from Pseudomonas aeruginosa), and its interaction with HEWL has been unraveled [13] [19]. "
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    ABSTRACT: The production of lysozyme inhibitors, competitively binding to the lysozyme active site, is a bacterial strategy to prevent the lytic activity of host lysozymes. Therefore, suppression of the lysozyme-inhibitor interaction is an interesting new approach for drug development since restoration of the bacterial lysozyme sensitivity will support bacterial clearance from the infected sites. Using molecular modelling techniques the interaction of the Salmonella PliC inhibitor with c-type lysozyme was studied and a protein-protein interaction based pharmacophore model was created. This model was used as a query to identify molecules, with potential affinity for the target, and subsequently, these molecules were filtered using molecular docking. The retained molecules were validated as suppressors of lysozyme inhibitory proteins using in vitro experiments revealing four active molecules.
    Biochemical and Biophysical Research Communications 02/2011; 405(4):527-32. DOI:10.1016/j.bbrc.2011.01.053 · 2.30 Impact Factor
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    • "Muramyl dipeptide (MDP), originally isolated from killed M. tuberculosis and an active component of Freund's complete adjuvant (Ellouz et al., 1974), is recognized by Nod2 (Benko et al., 2008). Generation of MDP requires the activity of a bacterial-specific endopeptidase (Humann and Lenz, 2008). Unlike TCT, its presence is not specific for growing bacteria and, in fact, the PGN cleavage that generates MDP also destroys TCT. "
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    ABSTRACT: The dominant conceptual framework for understanding innate immunity has been that host cells respond to evolutionarily conserved molecular features of pathogens called pathogen-associated molecular patterns (PAMPs). Here, we propose that PAMPs should be understood in the context of how they are naturally presented by pathogens. This can be experimentally challenging, since pathogens, almost by definition, bypass host defense. Nevertheless, in this review, we explore the idea that the immune system responds to PAMPs in the context of additional signals that derive from common "patterns of pathogenesis" employed by pathogens to infect, multiply within, and spread among their hosts.
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