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dc.contributor.authorKieser, Karen J.
dc.contributor.authorBoutte, Cara C.
dc.contributor.authorKester, Jemila C.
dc.contributor.authorBaer, Christina E.
dc.contributor.authorBarczak, Amy K.
dc.contributor.authorMeniche, Xavier
dc.contributor.authorChao, Michael C.
dc.contributor.authorRego, E Hesper
dc.contributor.authorSassetti, Christopher M.
dc.contributor.authorFortune, Sarah M.
dc.contributor.authorRubin, Eric J.
dc.date2022-08-11T08:09:42.000
dc.date.accessioned2022-08-23T16:40:41Z
dc.date.available2022-08-23T16:40:41Z
dc.date.issued2015-06-26
dc.date.submitted2015-07-23
dc.identifier.citationPLoS Pathog. 2015 Jun 26;11(6):e1005010. doi: 10.1371/journal.ppat.1005010. eCollection 2015. <a href="http://dx.doi.org/10.1371/journal.ppat.1005010">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1005010
dc.identifier.pmid26114871
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39733
dc.description.abstractCell 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26114871&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<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>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBacterial Infections and Mycoses
dc.subjectImmunology and Infectious Disease
dc.subjectMicrobiology
dc.titlePhosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume11
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3534&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2531
dc.identifier.contextkey7357729
refterms.dateFOA2022-08-23T16:40:42Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2531
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.source.pagese1005010


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<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>
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>