O-Acetylated peptidoglycan: Controlling the activity of bacterial autolysins and lytic enzymes of innate immune systems

Moynihan, Patrick J.; Clarke, Anthony J.

doi:10.1016/j.biocel.2011.08.007

Cited by 75 publications

(91 citation statements)

References 16 publications

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“…Given that their mode of action results in the production of 1,6-anhydromuramoyl reaction products, the lytic transglycosylases are dependent on Ape to remove any blocking O-acetyl groups. Consequently, Apes are proposed to play a major role in controlling PG metabolism (3).…”

Section: Discussionmentioning

confidence: 99%

“…Given this, we hypothesized the need for (4), and later demonstrated (5), the existence of a new class of enzymes that function to de-O-acetylate PG. These O-acetyl-PG esterases (Ape) appear to be ubiquitous in Gramnegative bacteria that O-acetylate their PG (3,4). A genomic study led to the identification of three families of enzymes, each with some amino acid sequence similarity to the family CE-3 O-acetylxylan esterases of the CAZy classification system (4).…”

Section: Peptidoglycan (Pg)mentioning

confidence: 99%

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Mechanism of Action of Neisseria gonorrhoeae O-Acetylpeptidoglycan Esterase, an SGNH Serine Esterase

Pfeffer

Weadge²,

Clarke

2013

Journal of Biological Chemistry

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Background: O-Acetylpeptidoglycan esterase functions to release O-acetyl groups from peptidoglycan, thereby permitting the continued metabolism of this essential cell wall component. Results: Gly-236 and Asn-268 were identified as participating at the oxyanion hole to stabilize the tetrahedral species in the reaction mechanism. Conclusion: Ape1a functions as a classical serine esterase. Significance: Ape represents a novel target for the development of new antibiotics.

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Section: Discussionmentioning

confidence: 99%

Section: Peptidoglycan (Pg)mentioning

confidence: 99%

Mechanism of Action of Neisseria gonorrhoeae O-Acetylpeptidoglycan Esterase, an SGNH Serine Esterase

Pfeffer

Weadge²,

Clarke

2013

Journal of Biological Chemistry

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“…The list includes important human pathogens, such as Staphylococcus aureus, Bacillus anthracis, all species of Enterococcus, species of Campylobacter, Listeria monocytogenes, Neisseria gonorrhoeae, and Neisseria meningitidis (reviewed in Ref. 1). This modification to PG occurs predominantly at the C-6 hydroxyl group of N-acetylmuramyl (MurNAc) residues, and it is particularly significant because it sterically hinders the activity of muramidases (lysozymes), thereby providing protection from the defensive activity of innate immune systems.…”

mentioning

confidence: 99%

Substrate Specificity and Kinetic Characterization of Peptidoglycan O-Acetyltransferase B from Neisseria gonorrhoeae

Moynihan

Clarke

2014

Journal of Biological Chemistry

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Background:The O-acetylation of peptidoglycan in Gram-negative bacteria is catalyzed by PatB. Results: PatB can utilize a variety of acetyl donors for transfer to polymerized glycans containing N-acetyl groups and muroglycans containing tri-and tetrapeptide stems. Conclusion: PatB has broad specificity for acetyl donors but narrow specificity for acceptor glycans. Significance: This information will help with the identification of possible leads to novel classes of antibiotics.

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“…This result suggests that C. jejuni may have additional O-acetyltransferases. Lysozyme resistance is considered to be the representative biological function of PG O-acetylation in both Gram-positive and Gram-negative bacteria (12,15). Lysozyme is an antimicrobial enzyme that is naturally present in the mucosal layer and in leukocytes, including macrophages (25).…”

Section: Figmentioning

confidence: 99%

“…Thus, the protein was renamed PG O-acetyltransferase B (PatB) (14). PatA and PatB have recently been proposed to function together in translocating acetate from cytoplasmic pools to the periplasm, where it is transferred to peptidoglycan in Gram-negative bacteria (15) (Fig. 1A).…”

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confidence: 99%

Peptidoglycan Acetylation of Campylobacter jejuni Is Essential for Maintaining Cell Wall Integrity and Colonization in Chicken Intestines

Iwata

Watanabe

Kusumoto

et al. 2016

Appl Environ Microbiol

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Peptidoglycan (PG) acetylation of Gram-positive bacteria confers lysozyme resistance and contributes to survival in the host. However, the importance of PG acetylation in Gram-negative bacteria has not been fully elucidated. The genes encoding putative PG acetyltransferase A (PatA) and B (PatB) are highly conserved in Campylobacter jejuni, the predominant cause of bacterial diarrhea worldwide. To evaluate the importance of PatA and PatB of C. jejuni, we constructed patA and patB isogenic mutants and compared their phenotypes with those of the parental strains. Although transmission electron microscopy did not reveal morphological changes, both mutants exhibited decreased motility and biofilm formation in vitro. The extent of acetylation of the PG purified from the patA and patB mutants was significantly lower than the PG acetylation in the parental strains. Both mutants exhibited decreased lysozyme resistance and intracellular survival in macrophage cells. In a chick colonization experiment, significant colonization deficiency was observed for both mutants. These results suggest that PatA and PatB of C. jejuni play important roles in maintaining cell wall integrity by catalyzing PG Oacetylation and that the loss of these enzymes causes decreased motility and biofilm formation, thus leading to colonization deficiency in chicken infection. IMPORTANCEThe importance of peptidoglycan (PG) acetylation in Gram-negative bacteria has not been fully elucidated. The genes encoding putative PG acetyltransferase A (PatA) and B (PatB) are highly conserved in Campylobacter jejuni, the predominant cause of bacterial diarrhea worldwide. We evaluated the importance of these enzymes using isogenic mutants. The results of this study suggest that PatA and PatB of C. jejuni play important roles in maintaining cell wall integrity. The loss of these factors caused multiple phenotypic changes, leading to colonization deficiency in chicken infection. These data should be useful in developing novel control measures to prevent chicken colonization by C. jejuni. Inhibitors of the PG acetylation enzymes PatA and PatB might serve as potent anti-C. jejuni agents. Campylobacter is one of the most common bacterial causes of diarrhea, of which there are approximately 400 million cases per year worldwide (1). Campylobacter jejuni colonizes the intestinal tracts of various wild and domestic animals, and avian species such as poultry are considered to be the main reservoir of this pathogen (2-5). Contaminated poultry meat is one of the principal sources of C. jejuni pathogenic to humans (6). The reduction of C. jejuni contamination in the food chain is an important step in the control of campylobacteriosis. One of the most important control points is the colonization of broiler chickens by C. jejuni. However, there are currently no measures in practical use to control Campylobacter infections in poultry.The helical morphology of C. jejuni is responsible for its enhanced ability, compared with that of rod-shaped bacteria, to move through the ...

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O-Acetylated peptidoglycan: Controlling the activity of bacterial autolysins and lytic enzymes of innate immune systems

Cited by 75 publications

References 16 publications

Mechanism of Action of Neisseria gonorrhoeae O-Acetylpeptidoglycan Esterase, an SGNH Serine Esterase

Mechanism of Action of Neisseria gonorrhoeae O-Acetylpeptidoglycan Esterase, an SGNH Serine Esterase

Substrate Specificity and Kinetic Characterization of Peptidoglycan O-Acetyltransferase B from Neisseria gonorrhoeae

Peptidoglycan Acetylation of Campylobacter jejuni Is Essential for Maintaining Cell Wall Integrity and Colonization in Chicken Intestines

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