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

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Mark van der Linden ◽  
Julia Otten ◽  
Carina Bergmann ◽  
Cristina Latorre ◽  
Josefina Liñares ◽  
...  
Keyword(s):  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Viridans Streptococci ◽  
Content Type ◽  
The Family ◽  
Biological Tests ◽  
Resistant Strains ◽  
National Reference Center ◽  
Partner Proteins

ABSTRACT 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.

scholarly journals Evaluation of an Immunochromatographic Assay for Rapid Detection of Penicillin-Binding Protein 2a in Human and Animal Staphylococcus intermedius Group, Staphylococcus lugdunensis, and Staphylococcus schleiferi Clinical Isolates

2015 ◽  
Vol 54 (3) ◽  
pp. 745-748 ◽  
Author(s):  
A. R. Arnold ◽  
C.-A. D. Burnham ◽  
B. A. Ford ◽  
S. D. Lawhon ◽  
S. K. McAllister ◽  
...  
Keyword(s):  
Rapid Detection ◽  
Binding Protein ◽  
Clinical Isolates ◽  
Immunochromatographic Assay ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Staphylococcus Lugdunensis ◽  
Content Type ◽  
Staphylococcus Intermedius ◽  
Detection Assay

The performance of a rapid penicillin-binding protein 2a (PBP2a) detection assay, the Alere PBP2a culture colony test, was evaluated for identification of PBP2a-mediated beta-lactam resistance in human and animal clinical isolates ofStaphylococcus intermediusgroup,Staphylococcus lugdunensis, andStaphylococcus schleiferi. The assay was sensitive and specific, with all PBP2a-negative and PBP2a-positive strains testing negative and positive, respectively.

scholarly journals Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis

2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Akuzike Kalizang'oma ◽  
Chrispin Chaguza ◽  
Andrea Gori ◽  
Charlotte Davison ◽  
Sandra Beleza ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Type Species ◽  
Binding Protein ◽  
Pneumococcal Serotypes ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Streptococcus Mitis ◽  
Content Type ◽  
Link Type ◽  
Close Relatives

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus , the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis , Streptococcus oralis and S. pneumoniae . With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis . Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced β-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis .

scholarly journals PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus

2016 ◽  
Vol 60 (7) ◽  
pp. 3934-3941 ◽  
Author(s):  
Liana C. Chan ◽  
Aubre Gilbert ◽  
Li Basuino ◽  
Thaina M. da Costa ◽  
Stephanie M. Hamilton ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Core Genome ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
High Level ◽  
New Generation ◽  
Level Resistance

ABSTRACTStaphylococcus aureusis an important cause of both hospital- and community-associated methicillin-resistantS. aureus(MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treatS. aureusinfections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance ofS. aureushas always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by themecAgene. Here, we show thatS. aureuscan also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams.

scholarly journals New Ceftriaxone- and Multidrug-Resistant Neisseria gonorrhoeae Strain with a Novel MosaicpenAGene Isolated in Japan

2016 ◽  
Vol 60 (7) ◽  
pp. 4339-4341 ◽  
Author(s):  
Shu-ichi Nakayama ◽  
Ken Shimuta ◽  
Kei-ichi Furubayashi ◽  
Takuya Kawahata ◽  
Magnus Unemo ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Multidrug Resistant ◽  
Terminal Region ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Gonorrhoeae Strain ◽  
Resistant Strains

ABSTRACTWe have characterized in detail a new ceftriaxone- and multidrug-resistantNeisseria gonorrhoeaestrain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaicpenAallele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3′-terminal region ofpenAwas almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread.

scholarly journals β-Lactam Antibiotics Targeting PBP1 Selectively Enhance Daptomycin Activity against Methicillin-Resistant Staphylococcus aureus

2013 ◽  
Vol 57 (10) ◽  
pp. 5005-5012 ◽  
Author(s):  
Andrew D. Berti ◽  
George Sakoulas ◽  
Victor Nizet ◽  
Ryan Tewhey ◽  
Warren E. Rose
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Protein ◽  
Membrane Insertion ◽  
Penicillin Binding Protein ◽  
Compensatory Response ◽  
Binding Profile ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTThe activity of daptomycin (DAP) against methicillin-resistantStaphylococcus aureus(MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal β-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different β-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different β-lactam antibiotics to determine if a specific PBP-binding profile is associated with the ability to enhance the anti-MRSA activity of DAP. We determined that both broad- and narrow-spectrum β-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas β-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by β-lactam antibiotics affects pathways of cell division inS. aureusthat may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.

scholarly journals A Low-Affinity Penicillin-Binding Protein 2x Variant Is Required for Heteroresistance in Streptococcus pneumoniae

2014 ◽  
Vol 58 (7) ◽  
pp. 3934-3941 ◽  
Author(s):  
Hansjürg Engel ◽  
Moana Mika ◽  
Dalia Denapaite ◽  
Regine Hakenbeck ◽  
Kathrin Mühlemann ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporter ◽  
Binding Protein ◽  
Population Analysis ◽  
Resistance Testing ◽  
Penicillin Binding Protein ◽  
Secondary Resistance ◽  
Content Type ◽  
Abc Transporter Genes

ABSTRACTHeteroresistance to penicillin inStreptococcus pneumoniaeis the ability of subpopulations to grow at a higher antibiotic concentration than expected from the MIC. This may render conventional resistance testing unreliable and lead to therapeutic failure. We investigated the role of the primary β-lactam resistance determinants, penicillin-binding protein 2b (PBP2b) and PBP2x, and the secondary resistance determinant PBP1a in heteroresistance to penicillin. Transformants containing PBP genes from the heteroresistant strain Spain23F2349in the nonheteroresistant strain R6 background were tested for heteroresistance by population analysis profiling (PAP). We found thatpbp2x, but notpbp2borpbp1aalone, conferred heteroresistance to R6. However, a change ofpbp2xexpression was not observed, and therefore, expression does not correlate with an increased proportion of resistant subpopulations. In addition, the influence of the CiaRH system, mediating PBP-independent β-lactam resistance, was assessed by PAP onciaRdisruption mutants but revealed no heteroresistant phenotype. We also showed that the highly resistant subpopulations (HOM*) of transformants containing low-affinitypbp2xundergo an increase in resistance upon selection on penicillin plates that partially reverts after passaging on selection-free medium. Shotgun proteomic analysis showed an upregulation of phosphate ABC transporter subunit proteins encoded bypstS,phoU,pstB, andpstCin these highly resistant subpopulations. In conclusion, the presence of low-affinitypbp2xenables certain pneumococcal colonies to survive in the presence of β-lactams. Upregulation of phosphate ABC transporter genes may represent a reversible adaptation to antibiotic stress.

scholarly journals Structural Insights into Ceftobiprole Inhibition of Pseudomonas aeruginosa Penicillin-Binding Protein 3

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Vijay Kumar ◽  
Christie Tang ◽  
Christopher R. Bethel ◽  
Krisztina M. Papp-Wallace ◽  
Jacob Wyatt ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Binding Protein ◽  
Covalent Bond ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Cephalosporin Antibiotic ◽  
Structural Insights ◽  
Fine Tune ◽  
Advanced Generation

ABSTRACT Ceftobiprole is an advanced-generation broad-spectrum cephalosporin antibiotic with potent and rapid bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, as well as susceptible Gram-negative pathogens, including Pseudomonas sp. pathogens. In the case of Pseudomonas aeruginosa, ceftobiprole acts by inhibiting P. aeruginosa penicillin-binding protein 3 (PBP3). Structural studies were pursued to elucidate the molecular details of this PBP inhibition. The crystal structure of the His-tagged PBP3-ceftobiprole complex revealed a covalent bond between the ligand and the catalytic residue S294. Ceftobiprole binding leads to large active site changes near binding sites for the pyrrolidinone and pyrrolidine rings. The S528 to L536 region adopts a conformation previously not observed in PBP3, including partial unwinding of the α11 helix. These molecular insights can lead to a deeper understanding of β-lactam-PBP interactions that result in major changes in protein structure, as well as suggesting how to fine-tune current inhibitors and to develop novel inhibitors of this PBP.

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