Transfer of penicillin resistance from <scp>S</scp>treptococcus oralis to <scp>S</scp>treptococcus pneumoniae identifies mur<scp>E</scp> as resistance determinant

Todorova, Katya; Maurer, Patrick; Rieger, Martin; Becker, Thorsten Hermann; Bui, Nhat Khai; Gray, Joe; Vollmer, Waldemar; Hakenbeck, Regine

doi:10.1111/mmi.13070

Cited by 23 publications

(18 citation statements)

References 62 publications

(90 reference statements)

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“…Both isolates also exhibited identical substitutions within MurE, a UDP-N-acetylmuramyl tripeptide synthetase. However, in the case of MurE, mutations in the promoter region leading to increased transcription levels have been shown to increase β-lactam resistance in Gram-positive species, particularly resistance to oxacillin [43, 46]. Thus, it remains unclear whether those substitutions have any impact on the phenotype.…”

Section: Resultsmentioning

confidence: 99%

Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B

Makarewicz¹,

Lucas²,

Brandt³

et al. 2017

PLoS ONE

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Streptococcus pneumoniae is a major pathogen that causes different invasive pneumococcal diseases (IPD). The pneumococcal polysaccharide capsule is a main virulence factor. More than 94 capsule types have been described, but only a limited number of capsule types accounted for the majority of IPD cases before the introduction of pneumococcal vaccines. After the introduction of the conjugated pneumococcal vaccine PCV7, which covered the seven most frequent serotypes in IPD in the USA, an increase in IPD caused by non-vaccine serotypes was observed, and serotype 19A, which belongs to sequence type (ST) 199, was among the most prevalent STs. After the introduction of the extended vaccine PCV13, which includes serotype 19A, serogroup 15B/C increased in IPD. Therefore, whole genome sequences of 39 isolates of ST199 from Germany (collected between 1998 and 2011) with serotype 19A (n = 24) and serogroup 15B/C (n = 15) were obtained using an Illumina platform and were analysed to identify capsular switches within ST199. Two 19A to 15B/C serotype switch events were identified. Both events occurred before the introduction of PCV7, which indicates that a capsular switch from 19A to 15B among ST199 isolates is not unusual and is not directly linked to the vaccination. The observed serotype replacement appears to be the result of a vacant niche due to the displacement of vaccine serotypes that is now successfully occupied by ST199 clones.

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Section: Resultsmentioning

confidence: 99%

Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B

Makarewicz¹,

Lucas²,

Brandt³

et al. 2017

PLoS ONE

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“…mitis and S. oralis DNA (48, 49). These data support the conclusion that it is not possible to deduce the number of gene transfer events that contribute to a mosaic gene structure.…”

Section: Discussionmentioning

confidence: 99%

Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci

Linden

Otten

Bergmann

et al. 2017

Antimicrob Agents Chemother

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The identification of commensal streptococci species is an everlasting problem due to their ability to genetically transform. A new challenge in this respect is the recent description of Streptococcus pseudopneumoniae as a new species, which was distinguished from closely related pathogenic S. pneumoniae and commensal S. mitis by a variety of physiological and molecular biological tests. Forty-one atypical S. pneumoniae isolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the species S. pseudopneumoniae. A comparison with the pbp2x sequences from 120 commensal streptococci isolated from different continents revealed that pbp2x is distinct among penicillin-susceptible S. pseudopneumoniae isolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitive S. mitis account for most of the diverse sequence blocks in resistant S. pseudopneumoniae, S. pneumoniae, and S. mitis, and S. infantis and S. oralis sequences were found in S. pneumoniae from Japan. PBP2x genes of the family of mosaic genes related to pbp2x in the S. pneumoniae clone Spain23F-1 were observed in S. oralis and S. infantis as well, confirming its global distribution. Thirty-eight sites were altered within the PBP2x transpeptidase domains of penicillin-resistant strains, excluding another 37 sites present in the reference genes of sensitive strains. Specific mutational patterns were detected depending on the parental sequence blocks, in agreement with distinct mutational pathways during the development of beta-lactam resistance. The majority of the mutations clustered around the active site, whereas others are likely to affect stability or interactions with the C-terminal domain or partner proteins.

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“…Unlike many other bacterial species that pick up genes for b-lactamases by horizontal gene transfer, S. pneumoniae acquires resistance to b-lactam antibiotics by mutations in its core PBPs (Zapun et al, 2008a;Hakenbeck et al, 2012). These resistance mutations can arise spontaneously and can be transferred by natural competence from related Streptococcus species to form mosaic pbp genes (Hakenbeck et al, 2012;Todorova et al, 2015). High-level b-lactam resistance is caused by combinations of mutations in pbp1a, pbp2x and pbp2b (Hakenbeck et al, 2012;Chewapreecha et al, 2014;Hakenbeck, 2014;Philippe et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in Streptococcus pneumoniae D39

Tsui

Zheng

Magallon

et al. 2016

Molecular Microbiology

269

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SUMMARY In ellipsoid-shaped ovococcus bacteria, such as the pathogen Streptococcus pneumoniae (pneumococcus), side-wall (peripheral) peptidoglycan (PG) synthesis emanates from midcells and is catalyzed by the essential class B penicillin-binding protein PBP2b transpeptidase (TP). We report that mutations that inactivate the pneumococcal YceG-domain protein, Spd_1346 (renamed MltG), remove the requirement for PBP2b. ΔmltG mutants in unencapsulated strains accumulate inactivation mutations of class A PBP1a, which possesses TP and transglycosylase (TG) activities. The “synthetic viable” genetic relationship between Δpbp1a and ΔmltG mutations extends to essential ΔmreCD and ΔrodZ mutations that misregulate peripheral PG synthesis. Remarkably, the single MltG(Y488D) change suppresses the requirement for PBP2b, MreCD, RodZ, and RodA. Structural modeling and comparisons, catalytic-site changes, and an interspecies chimera indicate that pneumococcal MltG is the functional homologue of the recently reported MltG endo-lytic transglycosylase of Escherichia coli. Depletion of pneumococcal MltG or mltG(Y488D) increases sphericity of cells, and MltG localizes with peripheral PG synthesis proteins during division. Finally, growth of Δpbp1a ΔmltG or mltG(Y488D) mutants depends on induction of expression of the WalRK TCS regulon of PG hydrolases. These results fit a model in which MltG releases anchored PG glycan strands synthesized by PBP1a for crosslinking by a PBP2b:RodA complex in peripheral PG synthesis.

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Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant

Cited by 23 publications

References 62 publications

Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B

Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B

Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci

Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in Streptococcus pneumoniae D39

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