Phosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria
Authors
Kieser, Karen J.Boutte, Cara C.
Kester, Jemila C.
Baer, Christina E
Barczak, Amy K.
Meniche, Xavier
Chao, Michael C.
Rego, E Hesper
Sassetti, Christopher M
Fortune, Sarah M.
Rubin, Eric J.
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Journal ArticlePublication Date
2015-06-26
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Cell growth and division are required for the progression of bacterial infections. Most rod-shaped bacteria grow by inserting new cell wall along their mid-section. However, mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce new cell wall material at their poles. How mycobacteria control this different mode of growth is incompletely understood. Here we find that PonA1, a penicillin binding protein (PBP) capable of transglycosylation and transpeptidation of cell wall peptidoglycan (PG), is a major governor of polar growth in mycobacteria. PonA1 is required for growth of Mycobacterium smegmatis and is critical for M. tuberculosis during infection. In both cases, PonA1's catalytic activities are both required for normal cell length, though loss of transglycosylase activity has a more pronounced effect than transpeptidation. Mutations that alter the amount or the activity of PonA1 result in abnormal formation of cell poles and changes in cell length. Moreover, altered PonA1 activity results in dramatic differences in antibiotic susceptibility, suggesting that a balance between the two enzymatic activities of PonA1 is critical for survival. We also find that phosphorylation of a cytoplasmic region of PonA1 is required for normal activity. Mutations in a critical phosphorylated residue affect transglycosylase activity and result in abnormal rates of cell elongation. Together, our data indicate that PonA1 is a central determinant of polar growth in mycobacteria, and its governance of cell elongation is required for robust cell fitness during both host-induced and antibiotic stress.Source
PLoS Pathog. 2015 Jun 26;11(6):e1005010. doi: 10.1371/journal.ppat.1005010. eCollection 2015. Link to article on publisher's siteDOI
10.1371/journal.ppat.1005010Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39733PubMed ID
26114871Related Resources
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Copyright: © 2015 Kieser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1005010
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Except where otherwise noted, this item's license is described as <p>Copyright: © 2015 Kieser et al. This is an open access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>