Another Brick in the Wall: the role of the actinobacterial cell wall in antibiotic resistance, phylogeny and development

Aart, L.T. van der (2019)

Doctoral Thesis

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle. This thesis shows the identification of S. roseifaciens, a novel species with an uncommon, verticillate spore morphology and a unique household of SsgA-like proteins. Analyses of the peptidoglycan composition show that S. coelicolor show a pattern of 3-3 cross-linking befitting a tip-growing organism and change in composition between vegetative mycelium and spores. Kitasatosporae carry meso-DAP in the peptidoglycan of vegetative mycelium and LL-DAP in the peptidoglycan of spores. In line with this difference, the peptidoglycan architecture of these two growth stages undergoes such radical changes that they would seem to be from different species. S. coelicolor is naturally vancomycin resistant, but the addition of D-alanine and disruption in a single gene increases vancomycin sensitivity by a thousandfold. A knockout mutant of the alanine racemase, alr, requires exogenous addition of D-alanine. The Alr crystal structure of S. coelicolor and the D-cycloserine producer S. lavendulae were compared as to look for possible mechanisms for D-cycloserine resistance. 

• Morphology
• Streptomyces
• Genetics
• Peptidoglycan
• Phylogeny
• Antibiotic resistance
• Cell wall

• All authors: Aart, L.T. van der
• Supervisor: Wezel, G.P. van; Hankemeier, T.
• Committee: Meijer, A.H.; Klinkhamer, P.G.L.; Bramkamp, M.; Rigali, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Institute of Biology Leiden (IBL), Faculty of Science, Leiden University
• Date: 2019-03-20