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Genetics of Peptidoglycan Biosynthesis

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  • Authors: Martin S. Pavelka Jr.1, Sebabrata Mahapatra2, Dean C. Crick3
  • Editors: Graham F. Hatfull4, William R. Jacobs Jr.5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: University of Rochester Medical Center, Department of Microbiology and Immunology, Rochester, NY 14642; 2: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523; 3: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523; 4: University of Pittsburgh, Pittsburgh, PA; 5: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY
    • Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
  • Received 06 September 2013 Accepted 14 October 2013 Published 01 August 2014
  • M. Pavelka, [email protected]
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  • Abstract:

    The complex cell envelope is a hallmark of mycobacteria and is anchored by the peptidoglycan layer, which is similar to that of and a number of other bacteria but with modifications to the monomeric units and other structural complexities that are likely related to a role for the peptidoglycan in stabilizing the mycolyl-arabinogalactan-peptidoglycan complex (MAPc). In this article, we will review the genetics of several aspects of peptidoglycan biosynthesis in mycobacteria, including the production of monomeric precursors in the cytoplasm, assembly of the monomers into the mature wall, cell wall turnover, and cell division. Finally, we will touch upon the resistance of mycobacteria to β-lactam antibiotics, an important class of drugs that, until recently, have not been extensively exploited as potential antimycobacterial agents. We will also note areas of research where there are still unanswered questions.

  • Citation: Pavelka Jr. M, Mahapatra S, Crick D. 2014. Genetics of Peptidoglycan Biosynthesis. Microbiol Spectrum 2(4):MGM2-0034-2013. doi:10.1128/microbiolspec.MGM2-0034-2013.

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/content/journal/microbiolspec/10.1128/microbiolspec.MGM2-0034-2013
2014-08-01
2020-02-21

Abstract:

The complex cell envelope is a hallmark of mycobacteria and is anchored by the peptidoglycan layer, which is similar to that of and a number of other bacteria but with modifications to the monomeric units and other structural complexities that are likely related to a role for the peptidoglycan in stabilizing the mycolyl-arabinogalactan-peptidoglycan complex (MAPc). In this article, we will review the genetics of several aspects of peptidoglycan biosynthesis in mycobacteria, including the production of monomeric precursors in the cytoplasm, assembly of the monomers into the mature wall, cell wall turnover, and cell division. Finally, we will touch upon the resistance of mycobacteria to β-lactam antibiotics, an important class of drugs that, until recently, have not been extensively exploited as potential antimycobacterial agents. We will also note areas of research where there are still unanswered questions.

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Genetics of Peptidoglycan Biosynthesis
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Citation: Pavelka Jr. M, Mahapatra S, Crick D. 2014. Genetics of peptidoglycan biosynthesis. microbiolspec 2(4): doi:10.1128/microbiolspec.MGM2-0034-2013
/content/microbiolspec/10.1128/microbiolspec.MGM2-0034-2013.fig1
FIGURE 1
PG nucleotide precursor (Park's nucleotide). Basic structure of the PG monomer precursor with the muropeptide -alanyl--glutaminyl--DAP--alanyl--alanine. R denotes the presence of either an -acetyl or -glycolyl modification of the muramic acid moiety. -Ala, -Glu, -DAP, and -Ala are depicted in gold, blue, green, and red, respectively.
microbiolspec/2/4/MGM2-0034-2013-fig1_thmb.gif
microbiolspec/2/4/MGM2-0034-2013-fig1.gif
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FIGURE 1

PG nucleotide precursor (Park's nucleotide). Basic structure of the PG monomer precursor with the muropeptide -alanyl--glutaminyl--DAP--alanyl--alanine. R denotes the presence of either an -acetyl or -glycolyl modification of the muramic acid moiety. -Ala, -Glu, -DAP, and -Ala are depicted in gold, blue, green, and red, respectively.

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
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FIGURE 2
PG cross-links. The direct 4-3 cross-link between -Ala and DAP. The direct 3-3 cross-link between two -DAP residues. Also shown are various modifications of the PG: R = H or disaccharide linker connecting the PG to the arabinan of the arabinogalactan; R = -acetyl or -glycolyl on the muramic acid residue; R = OH, NH or glycine; R = OH or NH. -Ala, -Glu, DAP, and -Ala are depicted in gold, blue, green, and red, respectively.
microbiolspec/2/4/MGM2-0034-2013-fig2_thmb.gif
microbiolspec/2/4/MGM2-0034-2013-fig2.gif
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FIGURE 2

PG cross-links. The direct 4-3 cross-link between -Ala and DAP. The direct 3-3 cross-link between two -DAP residues. Also shown are various modifications of the PG: R = H or disaccharide linker connecting the PG to the arabinan of the arabinogalactan; R = -acetyl or -glycolyl on the muramic acid residue; R = OH, NH or glycine; R = OH or NH. -Ala, -Glu, DAP, and -Ala are depicted in gold, blue, green, and red, respectively.

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
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FIGURE 3
Pathways for cytoplasmic steps of PG precursor synthesis.
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FIGURE 3

Pathways for cytoplasmic steps of PG precursor synthesis.

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
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FIGURE 4
Structure of the mycobacterial Lipid II PG precursor. R = N-acetyl or N-glycolyl on the muramic acid residue.
microbiolspec/2/4/MGM2-0034-2013-fig4_thmb.gif
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FIGURE 4

Structure of the mycobacterial Lipid II PG precursor. R = N-acetyl or N-glycolyl on the muramic acid residue.

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
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FIGURE 5
PG assembly proteins. The various PBPs and ,-transpeptidases are shown as they exist in the genome of . Gene designations from the H37Rv genome: (), (), (), (PBP3, , ), (PBP4, , ), (), (), (, ), (), (), (), (). These genes are also present in , with the exception of and , the latter of which is a pseudogene. and other soil organisms have the novel gene, an extra variant of , and an additional copy of the gene as described in the text. The various domains in each protein are also indicated. Note that PonA2 is unique because it bears a single PASTA domain, which likely binds unlinked PG precursors, and that PonA1, PonA2, LdtC, and LdtE bear extensive proline-rich regions. The class B PBP encoded by Rv2864c and the ,-transpeptidase encoded by are putative lipoproteins.
microbiolspec/2/4/MGM2-0034-2013-fig5_thmb.gif
microbiolspec/2/4/MGM2-0034-2013-fig5.gif
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FIGURE 5

PG assembly proteins. The various PBPs and ,-transpeptidases are shown as they exist in the genome of . Gene designations from the H37Rv genome: (), (), (), (PBP3, , ), (PBP4, , ), (), (), (, ), (), (), (), (). These genes are also present in , with the exception of and , the latter of which is a pseudogene. and other soil organisms have the novel gene, an extra variant of , and an additional copy of the gene as described in the text. The various domains in each protein are also indicated. Note that PonA2 is unique because it bears a single PASTA domain, which likely binds unlinked PG precursors, and that PonA1, PonA2, LdtC, and LdtE bear extensive proline-rich regions. The class B PBP encoded by Rv2864c and the ,-transpeptidase encoded by are putative lipoproteins.

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
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Tables

Genetics of Peptidoglycan Biosynthesis
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Citation: Pavelka Jr. M, Mahapatra S, Crick D. 2014. Genetics of peptidoglycan biosynthesis. microbiolspec 2(4): doi:10.1128/microbiolspec.MGM2-0034-2013
/content/microbiolspec/10.1128/microbiolspec.MGM2-0034-2013.T1
TABLE 1
Genes involved with PG turnover
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TABLE 1

Genes involved with PG turnover

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
/content/microbiolspec/10.1128/microbiolspec.MGM2-0034-2013.T2
TABLE 2
Genes involved with cell division
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TABLE 2

Genes involved with cell division

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013
/content/microbiolspec/10.1128/microbiolspec.MGM2-0034-2013.T3
TABLE 3
Genes involved with β-lactam antibiotic resistance
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TABLE 3

Genes involved with β-lactam antibiotic resistance

Source: microbiolspec August 2014 vol. 2 no. 4 doi:10.1128/microbiolspec.MGM2-0034-2013

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