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Peptidoglycan fragments released by Neisseria gonorrhoeae contribute to the inflammation and ciliated cell death associated with gonorrhea and pelvic inflammatory disease. However, little is known about the production and release of these fragments during bacterial growth. Previous studies demonstrated that one lytic transglycosylase, LtgA, was responsible for the production of approximately half of the released peptidoglycan monomers. Systematic mutational analysis of other putative lytic transglycosylase genes identified lytic transglycosylase D (LtgD) as responsible for release of peptidoglycan monomers from gonococci. An ltgA ltgD double mutant was found not to release peptidoglycan monomers and instead released large, soluble peptidoglycan fragments. In pulse-chase experiments, recycled peptidoglycan was not found in cytoplasmic extracts from the ltgA ltgD mutant as it was for the wild-type strain, indicating that generation of anhydro peptidoglycan monomers by lytic transglycosylases facilitates peptidoglycan recycling. The ltgA ltgD double mutant showed no growth abnormalities or cell separation defects, suggesting that these enzymes are involved in pathogenesis but not necessary for normal growth.Peptidoglycan (PG) fragments released during growth contribute to the pathogenesis of multiple bacterial infections, including those of Bordetella pertussis, Helicobacter pylori, and Neisseria gonorrhoeae (6,23,34). PG fragments induce the production of inflammatory cytokines, cause ciliated cell damage and fluid efflux, and trigger the Nod signaling cascade (reviewed in reference 5). Although PG fragments have been studied biochemically and for immunologic effects in multiple systems, the repertoire of genes and enzymes involved in PG fragment production and release from growing bacteria is unknown.PG fragments released from gram-negative bacterial pathogens are predicted to be produced by the action of lytic transglycosylases. Lytic transglycosylases cleave the N-acetylmuramic acid--1,4-N-acetylglucosamine linkage in PG and catalyze the formation of a 1,6-anhydro bond on the N-acetylmuramic acid (16). PG monomers released from N. gonorrhoeae and B. pertussis were shown to have the 1,6-anhydro bond, indicating that they were generated by lytic transglycosylases (26, 30). To identify genes for PG monomer production, we systematically mutated the genes for lytic transglycosylase homologues in N. gonorrhoeae. Mutation of lytic transglycosylase A (ltgA) resulted in a substantial decrease in PG monomers released (3). Mutations in lytic transglycosylase B (ltgB) or lytic transglycosylase C (ltgC) genes had no effect on PG monomer release (4, 19), although the ltgC mutant showed a severe defect in cell separation. These findings suggested the presence of other lytic transglycosylases in N. gonorrhoeae involved in release of PG monomers.Here we show that lytic transglycosylase LtgD is involved in the release of PG monomers. Additionally, we generated and characterized an N. gonorrhoeae strain deleted for both ltgA and...
Peptidoglycan fragments released by Neisseria gonorrhoeae contribute to the inflammation and ciliated cell death associated with gonorrhea and pelvic inflammatory disease. However, little is known about the production and release of these fragments during bacterial growth. Previous studies demonstrated that one lytic transglycosylase, LtgA, was responsible for the production of approximately half of the released peptidoglycan monomers. Systematic mutational analysis of other putative lytic transglycosylase genes identified lytic transglycosylase D (LtgD) as responsible for release of peptidoglycan monomers from gonococci. An ltgA ltgD double mutant was found not to release peptidoglycan monomers and instead released large, soluble peptidoglycan fragments. In pulse-chase experiments, recycled peptidoglycan was not found in cytoplasmic extracts from the ltgA ltgD mutant as it was for the wild-type strain, indicating that generation of anhydro peptidoglycan monomers by lytic transglycosylases facilitates peptidoglycan recycling. The ltgA ltgD double mutant showed no growth abnormalities or cell separation defects, suggesting that these enzymes are involved in pathogenesis but not necessary for normal growth.Peptidoglycan (PG) fragments released during growth contribute to the pathogenesis of multiple bacterial infections, including those of Bordetella pertussis, Helicobacter pylori, and Neisseria gonorrhoeae (6,23,34). PG fragments induce the production of inflammatory cytokines, cause ciliated cell damage and fluid efflux, and trigger the Nod signaling cascade (reviewed in reference 5). Although PG fragments have been studied biochemically and for immunologic effects in multiple systems, the repertoire of genes and enzymes involved in PG fragment production and release from growing bacteria is unknown.PG fragments released from gram-negative bacterial pathogens are predicted to be produced by the action of lytic transglycosylases. Lytic transglycosylases cleave the N-acetylmuramic acid--1,4-N-acetylglucosamine linkage in PG and catalyze the formation of a 1,6-anhydro bond on the N-acetylmuramic acid (16). PG monomers released from N. gonorrhoeae and B. pertussis were shown to have the 1,6-anhydro bond, indicating that they were generated by lytic transglycosylases (26, 30). To identify genes for PG monomer production, we systematically mutated the genes for lytic transglycosylase homologues in N. gonorrhoeae. Mutation of lytic transglycosylase A (ltgA) resulted in a substantial decrease in PG monomers released (3). Mutations in lytic transglycosylase B (ltgB) or lytic transglycosylase C (ltgC) genes had no effect on PG monomer release (4, 19), although the ltgC mutant showed a severe defect in cell separation. These findings suggested the presence of other lytic transglycosylases in N. gonorrhoeae involved in release of PG monomers.Here we show that lytic transglycosylase LtgD is involved in the release of PG monomers. Additionally, we generated and characterized an N. gonorrhoeae strain deleted for both ltgA and...
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