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- W2145023213 abstract "acid (DAP), a keycomponent ofa highly immunogenic subunit ofthemycobacterial peptidoglycan layer, hasbeen implicated as a potential virulence factor. Themycobacterial DAPbiosynthetic pathway could serveas a target fordesign ofnew antimycobacterial agents aswell as theconstruction ofinvivoselection systems. We have isolated theasd, dapA, dapB, dapD, anddapEgenesinvolved intheDAPbiosynthetic pathway ofMycobacterium bovis BCG.These geneswere isolated bycomplementation ofEscherichia coilmutations withan expression library ofBCG DNA. Ouranalysis ofthese genes suggests thatBCG may use more thanone pathway for biosynthesis ofDAP.Thenucleotide sequenceoftheBCG dapBgene was determined. Theactivity ofthe product ofthis gene inEscherichia coli provided evidence thatthegene may encode a novelbifunctional dihydrodipicolinate reductase andDAPdehydrogenase. Mycobacterial diseases, suchas tuberculosis andleprosy, currently causethehighest numberofdeaths ofanyinfectious disease throughout theworld(3). Inparticular, therecentrise intheincidence ofantibiotic-resistant tuberculosis inthe United States hasincreased theawarenessoftheimportance ofcontrolling thespread ofmycobacterial diseases. Ourlaboratoryhaschosen touse threemajorapproaches forthe development ofmethods tocombat mycobacterial diseases: (i) todevelop a further understanding ofthemechanisms that allow mycobacteria tocausedisease, (ii) tofind an effective andpractical methodofvaccination against mycobacteria, and (iii) toinvestigate potential methods oftreatment ofmycobacterial diseases. Tothis end, we havebeguntoexamine importantmycobacterial biosynthetic pathways that may beusedin thedevelopment ofmarkersystemsforuse inthestudy of pathogenesis, intheconstruction ofrecombinant vaccine strains, andaspotential targets fornew antibiotics. Diaminopimelic acid(DAP)isan essential componentof thepeptidoglycan layer ofmycobacterial cell walls, whichare knowntohaveunusual immunogenic potential. Interestingly, N-glucolylmuramyl-Lalanyl-D- isoglutaminyl -meso -diaminopimelate isan immunological adjuvant andenhances cellular andhumoral responsesinguinea pigs whenadministered with an antigen (9). Study ofthepathways involved inbiosynthesis ofthecell wall may leadtoabetter understanding ofthecauses oftheseimmunological effects. Thepeptidoglycan layer of mycobacteria hasunusual inter-DAP linkages aswellasthe standard DAP-D-alanine linkages (22). Thisfact results inan unusually highDAP content inthemycobacterial cell wall. The importance oftheDAP molecule hasbeenfurther suggested byworkwithBordetella pertussis, forwhichDAP hasbeen showntoplay a keyroleinthestructure ofa cytotoxin (13)." @default.
- W2145023213 created "2016-06-24" @default.
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- W2145023213 date "1994-01-01" @default.
- W2145023213 modified "2023-09-24" @default.
- W2145023213 title "Genetic Determination ofthemeso-Diaminopimelate Biosynthetic Pathway ofMycobacteria" @default.
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