We used reverse-phase high pressure liquid chromatography (HPLC), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and post source decay analysis (MALDI-PSD) to determine the muropeptide composition of the human pathogen Neisseria meningitidis. Structural assignment was determined for 28 muropeptide species isolated after HPLC separation and purification. Fourteen of these muropeptides were O-acetylated to different degrees. We identified the entire O-acetylation spectrum of dimers and trimers both in muropeptides and 1,6-anhydromuropeptides. On average, one of three disaccharides was O-acetylated. Furthermore, the degree of cross-linking of the N. meningitidis peptidoglycan was around 39% in all the strains analyzed. MALDI-PSD analysis of several muropeptide species indicated that meningococci only synthesize d-alanyl-meso-diaminopimelate cross-bridges. No muropeptides representative of covalent linkages of lipoproteins to the peptidoglycan could be identified, unlike in Escherichia coli. Finally, comparison of the muropeptide composition of penicillin-susceptible and penicillin-intermediate clinical strains of meningococci showed a positive correlation between the minimum inhibitory concentration (MIC) of penicillin G and the amount of muropeptides carrying an intact pentapeptide chain in the peptidoglycan. This suggests that reduced susceptibility to penicillin G in N. meningitidis is associated with a decrease in d,d-carboxypeptidase activity and/or d,d-transpeptidase activity. We used reverse-phase high pressure liquid chromatography (HPLC), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and post source decay analysis (MALDI-PSD) to determine the muropeptide composition of the human pathogen Neisseria meningitidis. Structural assignment was determined for 28 muropeptide species isolated after HPLC separation and purification. Fourteen of these muropeptides were O-acetylated to different degrees. We identified the entire O-acetylation spectrum of dimers and trimers both in muropeptides and 1,6-anhydromuropeptides. On average, one of three disaccharides was O-acetylated. Furthermore, the degree of cross-linking of the N. meningitidis peptidoglycan was around 39% in all the strains analyzed. MALDI-PSD analysis of several muropeptide species indicated that meningococci only synthesize d-alanyl-meso-diaminopimelate cross-bridges. No muropeptides representative of covalent linkages of lipoproteins to the peptidoglycan could be identified, unlike in Escherichia coli. Finally, comparison of the muropeptide composition of penicillin-susceptible and penicillin-intermediate clinical strains of meningococci showed a positive correlation between the minimum inhibitory concentration (MIC) of penicillin G and the amount of muropeptides carrying an intact pentapeptide chain in the peptidoglycan. This suggests that reduced susceptibility to penicillin G in N. meningitidis is associated with a decrease in d,d-carboxypeptidase activity and/or d,d-transpeptidase activity. Neisseria meningitidis is a major human pathogen that is capable of crossing the nasopharyngeal epithelial barrier to induce septicemia and meningitis (1Taha M.K. Deghmane A.E. Antignac A. Zarantonelli M.L. Larribe M. Alonso J.M. Trends Microbiol. 2002; 10: 376-382Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). Penicillin is considered to be the treatment of choice for meningococcal diseases due to the intrinsic susceptibility of N. meningitidis to β-lactam antibiotics. Indeed, few N. meningitidis strains carry plasmid-encoded β-lactamases. However, meningococcal strains with reduced susceptibility to penicillin due to a decreased affinity of the penicillin-binding protein 2 (PBP2) 1The abbreviations used are: PBP, penicillin-binding protein; HPLC, high pressure liquid chromatography; MALDI-MS, matrix-assisted laser desorption ionization mass spectrometry; PSD, post source decay; GlcNAc, N-acetylglucosamine; MurNAc, N-acetylmuramic acid; A2pm, diaminopimelic acid; MIC, minimum inhibitory concentration.1The abbreviations used are: PBP, penicillin-binding protein; HPLC, high pressure liquid chromatography; MALDI-MS, matrix-assisted laser desorption ionization mass spectrometry; PSD, post source decay; GlcNAc, N-acetylglucosamine; MurNAc, N-acetylmuramic acid; A2pm, diaminopimelic acid; MIC, minimum inhibitory concentration. associated with mosaic penA genes (2Bowler L.D. Zhang Q.Y. Riou J.Y. Spratt B.G. J. Bacteriol. 1994; 176: 333-337Crossref PubMed Google Scholar, 3Antignac A. Kriz P. Tzanakaki G. Alonso J.M. Taha M.K. J. Antimicrob. Chemother. 2001; 47: 285-296Crossref PubMed Scopus (46) Google Scholar) have been reported worldwide (4Oppenheim B.A. Clin. Infect. Dis. 1997; 24: 98-101Crossref PubMed Google Scholar). The penA gene codes for the PBP2, which is homologous to high molecular weight class B PBPs and is closely related to Escherichia coli PBP3 and Streptococcus pneumoniae PBP2x. Therefore, reduced susceptibility to penicillin G in N. meningitidis is expected to be associated with changes in the peptidoglycan structure, as previously seen in S. pneumoniae (5Garcia-Bustos J. Tomasz A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 5415-5419Crossref PubMed Scopus (118) Google Scholar), Haemophilus influenzae (6Burroughs M.H. Chang Y.S. Gage D.A. Tuomanen E.I. J. Biol. Chem. 1993; 268: 11594-11598Abstract Full Text PDF PubMed Google Scholar), and the related human pathogen Neisseria gonorrhoeae (7Dougherty T.J. Antimicrob. Agents Chemother. 1985; 28: 90-95Crossref PubMed Scopus (19) Google Scholar). Several virulence factors are involved in bacteria-host interactions and are responsible for preventing bacterial clearance and allowing colonization. However, little is known about the role of peptidoglycan in meningococcal pathogenesis, partly because the structure of the N. meningitidis peptidoglycan is not known. Indeed, besides the central roles of peptidoglycan in bacterial growth, shape maintenance and cell division, there is an increasing amount of evidence suggesting that its degradation products play a major biological role in the innate immune response of the host. The tracheal cytotoxin from Bordetella pertussis is a peptidoglycan degradation product, GlcNAc-(β-1,4)-1,6-anhydromuramyl-l -alanyl-d-glutamyl-meso-diaminopimelate-d-alanine (8Luker K.E. Collier J.L. Kolodziej E.W. Marshall G.R. Goldman W.E. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 2365-2369Crossref PubMed Scopus (53) Google Scholar). The same product from N. gonorrhoeae is cytotoxic for human fallopian tube epithelial cells (9Melly M.A. McGee Z.A. Rosenthal R.S. J. Infect. Dis. 1984; 149: 378-386Crossref PubMed Scopus (128) Google Scholar). Furthermore, several different muropeptides induce somnogenic, pyrogenic, and hematological effects (10Johannsen L. Rosenthal R.S. Martin S.A. Cady A.B. Obal Jr., F. Guinand M. Krueger J.M. Infect. Immun. 1989; 57: 2726-2732Crossref PubMed Google Scholar, 11Johannsen L. Toth L.A. Rosenthal R.S. Opp M.R. Obal Jr., F. Cady A.B. Krueger J.M. Am. J. Physiol. 1990; 258: R182-R186PubMed Google Scholar), which are directly relevant to the pathogenesis of N. meningitidis. Accordingly, N. gonorrhoeae has been used as a model organism to study the peptidoglycan of Neisseria spp., with particular emphasis on its structure and the biological activity of its degradation products (9Melly M.A. McGee Z.A. Rosenthal R.S. J. Infect. Dis. 1984; 149: 378-386Crossref PubMed Scopus (128) Google Scholar, 12Dougherty T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar, 13Martin S.A. Rosenthal R.S. Biemann K. J. Biol. Chem. 1987; 262: 7514-7522Abstract Full Text PDF PubMed Google Scholar, 14Cloud K.A. Dillard J.P. Infect. Immun. 2002; 70: 2752-2757Crossref PubMed Scopus (59) Google Scholar). However, the structural analysis of muropeptide species was only partial. Interestingly, N. meningitidis is cytopathic to human nasopharyngeal epithelial cells, which constitute the first line of host defense (15Stephens D.S. McGee Z.A. Cooper M.D. Antonie Van Leeuwenhoek. 1987; 53: 575-584Crossref PubMed Scopus (23) Google Scholar). The importance of penicillin resistance in meningococcal infection treatment failure and the potential biological properties of its peptidoglycan led us to perform a detailed structural analysis of the muropeptide composition of N. meningitidis using reverse-phase high pressure liquid chromatography (HPLC), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and post source decay analysis (MALDI-PSD). In addition, we compared the peptidoglycan composition of a series of clinical meningococcal strains with different levels of reduced susceptibility to penicillin G. Bacterial Strains and Growth Conditions—The meningococcal strains used in this study were isolated from clinical samples and characterized at the French National Reference Center for Meningococci (Table I). N. meningitidis was grown on GCB medium (Difco) containing Kellogg supplements (16Kellogg D.S. Peacock W.L. Deacon W.E. Brown L. Pirkle C.I. J. Bacteriol. 1963; 85: 1274-1279Crossref PubMed Google Scholar). Serological typing was performed as previously described (17Frasch C.E. Zollinger W.D. Poolman J.T. Rev. Infect. Dis. 1985; 7: 504-510Crossref PubMed Scopus (347) Google Scholar, 18Abdillahi H. Poolman J.T. FEMS Microbiol. Lett. 1987; 48: 367-371Crossref Scopus (220) Google Scholar). Penicillin G, amoxicillin, and cefotaxime susceptibilities were tested by the diffusion method (Etest) on G medium (Sanofi Diagnostic Pasteur), and the polymorphism of the penA gene was analyzed by restriction fragment length polymorphism as previously described (3Antignac A. Kriz P. Tzanakaki G. Alonso J.M. Taha M.K. J. Antimicrob. Chemother. 2001; 47: 285-296Crossref PubMed Scopus (46) Google Scholar).Table ICharacteristics of meningococcal strainsStrainCountry/year isolatedAnatomic siteSerogroup:serotype: serosubtypeMICpenA allelecThe polymorphism of the penA gene was analyzed by restriction fragment length polymorphism. (HaeIII-HpaII-TaqI)Penicillin GaMICs: susceptible <0.125 μg/ml; resistant >1 μg/ml.AmoxicillinbMICs: susceptible <0.5 μg/ml; resistant >2 μg/ml.CefotaximebMICs: susceptible <0.5 μg/ml; resistant >2 μg/ml.μg/mlLNP8013France/1989BloodC:NT:NST0.0940.0940.006penA1 (1-1-1)LNP20038France/2002Cerebrospinal fluidC:4:P1-10.0060.0940.006penA2 (1-6-1)LNP20057France/2002Cerebrospinal fluidB:14:P1-7,160.0320.0940.004penA1 (1-1-1)LNP16454France/1998ExpectorationC:2a:P1-5110.016penA7 (4-5-5)LNP16504France/1999Cerebrospinal fluidB:NT:NST0.250.380.008penA8 (5-7-6)LNP17041France/1999UnknownB:1:NST0.50.750.012penA26 (17-5-16)LNP16519France/1999Cerebrospinal fluidC:2a:P1-50.380.50.008penA7 (4-5-5)W-39Greece/1996Cerebrospinal fluidC:NT:P1-100.250.750.004penA5 (2-3-3)LNP17723France/2000Cerebrospinal fluidC:2a:P1-50.750.750.032penA7 (4-5-5)LNP18425France/2001Cerebrospinal fluidB:15:P1-1,7110.023penA7 (4-5-5)a MICs: susceptible <0.125 μg/ml; resistant >1 μg/ml.b MICs: susceptible <0.5 μg/ml; resistant >2 μg/ml.c The polymorphism of the penA gene was analyzed by restriction fragment length polymorphism. Open table in a new tab Peptidoglycan Preparation—Meningococci were inoculated in 500 ml of GCB liquid and incubated at 37 °C in a 5% CO2 atmosphere until the optical density at 600 nm reached 0.6–0.7. Peptidoglycan was isolated by an adapted version of the method developed for E. coli (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar). Cultures were swirled in ice-alcohol baths and then centrifuged at 8,000 × g for 30 min at 4 °C. The cells were washed once with and in ml of the same The cells were to ml of with and for a 30 to the was by at × g for 30 The was washed with and in ml of and and were at a concentration of and for 2 at 37 °C. The were by with of at 37 °C. The was with for The was and washed by as described The peptidoglycan was in and at °C. The peptidoglycan was in and with of from for at 37 °C. The was by the for and were by The peptidoglycan was with an of in which been for min at was with the of the samples was to and the samples were HPLC and of HPLC we used a from with to for to containing for min on a × at using a of was at muropeptides were by HPLC on the same using a in the HPLC were in muropeptide species that were a and The muropeptides were and at °C. muropeptides were analyzed by using as the as previously described N. Gage D.A. Anal. Biochem. 1997; PubMed Scopus Google Scholar). samples were a directly on the and analyzed using as the muropeptides were in of of the and of a of were the × 2 were at and washed for 30 with of the liquid with a samples were with of were on a with a laser The was in the and in the were in the with an of and a of mass spectrum was an of laser were using with a of the was used to the of the of N. meningitidis the peptidoglycan from the penicillin-susceptible was analyzed by reverse-phase HPLC and used as source for structural The molecular mass of was determined by This us to to 28 muropeptides in the peptidoglycan of N. meningitidis (Table and in Several of different could be the not allowing us to determine the major species analysis by of meningococcal muropeptides isolated by to not molecular due to the in these of a that muropeptide pentapeptide acid; O-acetylation on N-acetylmuramic muropeptide muropeptide in in muropeptides were in muropeptides were in to not molecular due to the in these of a that muropeptide pentapeptide acid; O-acetylation on N-acetylmuramic muropeptide in muropeptides were in Open table in a new tab analysis of muropeptides and MALDI-PSD was after HPLC and after The was for detailed of fragment P. F. B. J. Am. 10: PubMed Scopus Google Scholar) and and a to from the and to from the analysis of muropeptides and MALDI-PSD was after HPLC and after The was for detailed of fragment P. F. B. J. Am. 10: PubMed Scopus Google Scholar) and and a to from the and to from the The used to the meningococcal muropeptides from described by (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar). separation was the was at at °C. was not to by directly the HPLC muropeptide of E. coli and N. meningitidis. Therefore, several major muropeptide were analyzed by 2 the MALDI-PSD of muropeptides and The molecular of these muropeptides of and are with several Indeed, muropeptide be and muropeptide to the O-acetylated of muropeptide The MALDI-PSD of both of these muropeptides a fragment that to suggesting that both are This is by the of a a in the MALDI-PSD of Therefore, the muropeptide and its O-acetylated to and not to from activity. Furthermore, the MALDI-PSD of muropeptide a to the an In the positive muropeptides fragment from the as N. Gage D.A. Anal. Biochem. 1997; PubMed Scopus Google Scholar). Therefore, the is at the which is with the structure of Finally, the MALDI-PSD of muropeptide indicated that this muropeptide is of and the of of and to and an that this an at its We that muropeptide to the muropeptide carrying an the structural assignment of these three major the molecular of the muropeptides and compared with these major and the of the to structure (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar), we were to to all muropeptides species (Table Interestingly, were between the N. meningitidis and the related pathogen N. gonorrhoeae (7Dougherty T.J. Antimicrob. Agents Chemother. 1985; 28: 90-95Crossref PubMed Scopus (19) Google Scholar, 12Dougherty T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar). We evidence of muropeptides carrying in N. meningitidis as in T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar, 13Martin S.A. Rosenthal R.S. Biemann K. J. Biol. Chem. 1987; 262: 7514-7522Abstract Full Text PDF PubMed Google Scholar). Furthermore, the of O-acetylation of dimers and trimers in meningococci and in T.J. Antimicrob. Agents Chemother. 1987; PubMed Scopus Google Scholar). We were to the of to the length of meningococcal In with muropeptides that the major of the HPLC muropeptides and and Finally, to the by T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar), the of in peptidoglycan to in E. coli B. U. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar), we evidence for in with trimers the muropeptide species of and analysis us to the degree of cross-linking and of the of muropeptide in were one muropeptide was to be the major species in a and for the of we to to be the only structure, several of the different muropeptides in a were in In the was to We the degree of cross-linking to (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar) and a of around for with that determined for (6Burroughs M.H. Chang Y.S. Gage D.A. Tuomanen E.I. J. Biol. Chem. 1993; 268: 11594-11598Abstract Full Text PDF PubMed Google Scholar, B. U. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar, M. M.A. FEMS Microbiol. Lett. PubMed Google Scholar, E. J. S. K. Gage J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar). The degree of O-acetylation was as dimers trimers dimers trimers that we used the and not the of muropeptide for that we the of disaccharides directly We that one in three disaccharides is which is to for J. Microbiol. PubMed Scopus Google Scholar). us to an to the in of a muropeptide by O-acetylation the by min by the of of a the of a with one O-acetylated be min that of the both disaccharides are O-acetylated be min on this we were to and in a of min (Table The were to the in all for the major of and of muropeptides to degree of pentapeptide acid; O-acetylation on N-acetylmuramic were from to the muropeptide of × of pentapeptide acid; O-acetylation on N-acetylmuramic were from to the muropeptide of × of Open table in a new tab of the of the for penicillin-susceptible and penicillin-intermediate meningococcal strains mosaic penA genes (Table I). Penicillin G from to (Table I). of the HPLC of the different strains not major No new were in the penicillin-intermediate strains compared with the three susceptible that the resistance not due to a from to as in J.L. M. B. J. L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J.L. M. J. M. Van J. L. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus (63) Google Scholar). in the degree of cross-linking and O-acetylation to be associated with the with the resistance The of cross-linking was between and the of O-acetylation was between and Furthermore, the amount of muropeptides carrying to to the of and correlation was with in the amount of and that in the peptidoglycan of However, the of muropeptides carrying a pentapeptide we a correlation between penicillin G of the and the of pentapeptide in the meningococcal peptidoglycan (Table and composition of N. meningitidis penicillin-susceptible and penicillin-intermediate are as in to the the muropeptide to to the dimers trimers dimers trimers of muropeptide carrying the chain as a as an chain in a a of muropeptide carrying the chain as a as an chain in a a of muropeptide carrying the chain as a as an chain in a a of muropeptide carrying the chain as a as an chain in a a HPLC are as in to the the muropeptide to (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google to the dimers trimers dimers trimers of muropeptide carrying the chain as a as an chain in a a Open table in a new tab We characterized the composition and the degree of cross-linking and O-acetylation of the peptidoglycan from N. meningitidis in This to determine the roles of these structural in meningococcal Indeed, peptidoglycan O-acetylation in resistance to and to J. Microbiol. PubMed Scopus Google Scholar). has been that this the of the in the host by However, that peptidoglycan are molecular by the innate immune J. M. A. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N. A. F. J. K. S. S. M. J.L. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). O-acetylation be a bacterial that the of the host to these peptidoglycan to a response to This N. meningitidis to the epithelial barrier a response by the The O-acetylation of its peptidoglycan is a potential The same be for peptidoglycan as the in Tomasz A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Tomasz A. Infect. Immun. 2002; 70: PubMed Scopus Google Scholar). of was known about the structure of Neisseria was from for the closely related pathogen N. gonorrhoeae (7Dougherty T.J. Antimicrob. Agents Chemother. 1985; 28: 90-95Crossref PubMed Scopus (19) Google Scholar, 12Dougherty T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar, 13Martin S.A. Rosenthal R.S. Biemann K. J. Biol. Chem. 1987; 262: 7514-7522Abstract Full Text PDF PubMed Google Scholar). However, these were to the major muropeptide and to determine the of muropeptide analysis could of the different This us to different O-acetylated Furthermore, besides the of the we that dimers and trimers were O-acetylated (Table We the same of as Martin S.A. Rosenthal R.S. Biemann K. J. Biol. Chem. 1987; 262: 7514-7522Abstract Full Text PDF PubMed Google Scholar), with the of muropeptides carrying the on the muropeptides were by and T.J. Antimicrob. Agents Chemother. 1987; PubMed Scopus Google Scholar). The of has been reported for B. U. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar). However, this different as for N. Gage D.A. Anal. Biochem. 1997; PubMed Scopus Google Scholar). The of the muropeptide composition of the in particular of dimers and could not the of the of cross-bridges. these are due to we to determine meningococci and Neisseria are to synthesize muropeptides were first described in the peptidoglycan of E. coli (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar, B. U. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar) and have been to be associated with β-lactam resistance in J.L. M. B. J. L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Meningococci major muropeptides with because are susceptible to penicillin and β-lactam antibiotics. Furthermore, MALDI-PSD analysis of the major muropeptides and indicated that these muropeptides of 2 which the of major activity. on the of muropeptide muropeptides and a and its which of and we that these muropeptides have a In muropeptides and have (19Glauner B. Anal. Biochem. 1988; 172: 451-464Crossref PubMed Scopus (344) Google Scholar), in particular muropeptide which have been expected to at about min at we evidence for the of in N. meningitidis. particular of the N. meningitidis peptidoglycan is the of trimers B. U. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar) and of muropeptides from lipoproteins as in E. coli U. J. Biochem. PubMed Scopus Google Scholar). described the of in T.J. J. Bacteriol. 1985; 163: 69-74Crossref PubMed Google Scholar) after using to However, only trimers T.J. Antimicrob. Agents Chemother. 1987; PubMed Scopus Google Scholar), in with Neisseria peptidoglycan of a of In the of the HPLC due to the of the peptidoglycan of Neisseria has muropeptide that of E. coli. that N. meningitidis not a covalent of the lipoproteins for cell Finally, we compared the muropeptide of several meningococcal strains with different levels of susceptibility to penicillin G. susceptibility to penicillin in N. meningitidis not to be with new a in the of the as a for as in and (5Garcia-Bustos J. Tomasz A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 5415-5419Crossref PubMed Scopus (118) Google Scholar, J.L. M. B. J. L. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J.L. M. J. M. Van J. L. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus (63) Google Scholar, N. Gage D.A. Tomasz A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, we not in the degree of cross-linking between the as is the in S. strains N. Gage D.A. Tomasz A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Bacteriol. 1997; PubMed Google Scholar, M. B. PubMed Scopus Google Scholar). In H. resistance has been to be associated with an in This an in the activity of a which in the cell (6Burroughs M.H. Chang Y.S. Gage D.A. Tuomanen E.I. J. Biol. Chem. 1993; 268: 11594-11598Abstract Full Text PDF PubMed Google Scholar). we compared the of pentapeptide the meningococcal peptidoglycan we a correlation between penicillin G and the amount of muropeptides carrying an intact pentapeptide (Table and However, the in trimers were the different of the This in pentapeptide suggests that the peptidoglycan of meningococcal penicillin-intermediate strains is to peptidoglycan This is a the susceptible as that meningococci not capable of In the of penicillin-intermediate strains have to new peptidoglycan and to increasing the of in the peptidoglycan for the to with the of penicillin by for the of susceptibility to penicillin in N. meningitidis has been to be associated with mosaic penA genes (2Bowler L.D. Zhang Q.Y. Riou J.Y. Spratt B.G. J. Bacteriol. 1994; 176: 333-337Crossref PubMed Google Scholar, 3Antignac A. Kriz P. Tzanakaki G. Alonso J.M. Taha M.K. J. Antimicrob. Chemother. 2001; 47: 285-296Crossref PubMed Scopus (46) Google Scholar). penicillin-intermediate strains tested an penA different from that of the penicillin-susceptible as by restriction fragment length polymorphism analysis (Table I). This suggests that the changes in the peptidoglycan of strains are associated with in The of pentapeptide is a of peptidoglycan that has not been by This suggests a decrease in d,d-carboxypeptidase activity in penicillin-intermediate strains that has not been identified in N. meningitidis. In are by molecular weight PBPs J.M. Microbiol. Biol. Rev. PubMed Google Scholar). Indeed, the analysis of meningococcal strains the of three of these molecular weight PBP3 J. M. G. Brown P. K. N. S. K. S. S. K. M.A. M.A. M. J. S. Spratt B.G. B.G. PubMed Scopus Google Scholar, H. J. K.E. K.A. M.L. B.A. A. D.S. E. H. M.D. H. H. J. J. M. G. L. PubMed Scopus Google Scholar). to the high molecular weight class B PBPs and to the of peptidoglycan to as a However, that the have d,d-carboxypeptidase activity. The of pentapeptide as could d,d-transpeptidase activity of is that both d,d-transpeptidase and d,d-carboxypeptidase are However, we not a decrease in the degree of cross-linking that be due to the that we the of peptidoglycan that the decreased d,d-transpeptidase activity of is by the d,d-transpeptidase activity of the meningococcal which to the high molecular weight class of strains carrying and penA genes to determine the role of in the N. meningitidis peptidoglycan A. A. A. Alonso Taha J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (46) Google Scholar).
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