Draft Genome Sequences of Two Streptococcus pneumoniae Serotype 19A Sequence Type 226 Clinical Isolates from Hungary, Hu17 with High-Level Beta-Lactam Resistance and Hu15 of a Penicillin-Sensitive Phenotype

Rieger, Martin; Denapaite, Dalia; Brückner, Reinhold; Maurer, Patrick; Hakenbeck, Regine

doi:10.1128/genomea.00401-17

Cited by 2 publications

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“…To identify penicillin resistance determinants, two strains of ST226 were chosen for genome sequencing: Hu17, which is one of the strains with the highest levels of penicillin and cefotaxime resistance held in the Kaiserslautern strain (KL) collection, and penicillin-sensitive strain Hu15 ( 60 ). Genes encoding the resistance determinants PBP2x, PBP2b, PBP1a, and MurM were analyzed in detail.…”

Section: Resultsmentioning

confidence: 99%

“…In this work, we studied the resistance determinants in two serotype 19A strains from Hungary, strains Hu15 and Hu17. They represent members of the same clone, ST226, a single-locus variant of Hungary 19A -6 differing in the ddl allele, encoding the d -Ala– d -Ala ligase ( 60 ). Strain Hu15 is penicillin sensitive, whereas strain Hu17 exhibits high-level penicillin resistance; their MIC values for benzylpenicillin are 0.06 μg/ml and 24 μg/ml, respectively ( 57 ).…”

Section: Introductionmentioning

confidence: 99%

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New Aspects of the Interplay between Penicillin Binding Proteins, murM , and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary

Schweizer

Blättner

Maurer

et al. 2017

Antimicrob Agents Chemother

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The Streptococcus pneumoniae clone Hungary19A-6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232, encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104–3112, 2011, https://doi.org/10.1099/mic.0.053157-0). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary19A-6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x, pbp1a, murM, and ciaH, and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 (murMHu17), which is highly similar to murM of Streptococcus mitis, induced morphological changes which were partly reversed by ciaH232. murMHu17 conferred cefotaxime resistance only in the presence of the pbp2x of strain Hu17 (pbp2xHu17). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2xHu17 and pbp1a of strain Hu17 (pbp1aHu17), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1aHu17-mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%