Sandra M. Carvalho, Tomas G. Kloosterman, Irfan Manzoor, José Caldas, Susana Vinga, Jan Martinussen, Lígia M. Saraiva, Oscar P. Kuipers, Ana R. Neves
Abstract
Pyrimidine nucleotides play an important role in the biosynthesis of activated nucleotide sugars (NDP-sugars). NDP-sugars are the precursors of structural polysaccharides in bacteria, including capsule, which is a major virulence factor of the human pathogenS. pneumoniae. In this work, we identified a spontaneous non-reversible mutant of strain D39 that displayed a non-producing capsule phenotype. Whole-genome sequencing analysis of this mutant revealed several non-synonymous single base modifications, including in genes of thede novosynthesis of pyrimidines and in the -10 box of capsule operon promoter (Pcps). By directed mutagenesis we showed that the point mutation in Pcpswas solely responsible for the drastic decrease in capsule expression. We also demonstrated that D39 subjected to uracil deprivation shows increased biomass and decreased Pcpsactivity and capsule amounts. Importantly, Pcpsexpression is further decreased by mutating the first gene of thede novosynthesis of pyrimidines,carA. In contrast, the absence of uracil from the culture medium showed no effect on the spontaneous mutant strain. Co-cultivation of the wild-type and the mutant strain indicated a competitive advantage of the spontaneous mutant (non-producing capsule) in medium devoid of uracil. We propose a model in that uracil may act as a signal for the production of different capsule amounts inS. pneumoniae.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2018.
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#7,232,623
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Altmetric has tracked 23,025,074 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 25,153 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has gotten more attention than average, scoring higher than 69% of its peers.
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