scholarly journals Identification of Functional Regulatory Residues of the β-Lactam Inducible Penicillin Binding Protein in Methicillin-Resistant Staphylococcus aureus

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Andreas N. Mbah ◽  
Raphael D. Isokpehi
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Site ◽  
Binding Protein ◽  
Clinical Problem ◽  
Structural Features ◽  
Chemotherapeutic Agents ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant ◽  
Regulatory Analysis ◽  
New Protein

Resistance to methicillin by Staphylococcus aureus is a persistent clinical problem worldwide. A mechanism for resistance has been proposed in which methicillin resistant Staphylococcus aureus (MRSA) isolates acquired a new protein called β-lactam inducible penicillin binding protein (PBP-2′). The PBP-2′ functions by substituting other penicillin binding proteins which have been inhibited by β-lactam antibiotics. Presently, there is no structural and regulatory information on PBP-2′ protein. We conducted a complete structural and functional regulatory analysis of PBP-2′ protein. Our analysis revealed that the PBP-2′ is very stable with more hydrophilic amino acids expressing antigenic sites. PBP-2′ has three striking regulatory points constituted by first penicillin binding site at Ser25, second penicillin binding site at Ser405, and finally a single metallic ligand binding site at Glu657 which binds to Zn2+ ions. This report highlights structural features of PBP-2′ that can serve as targets for developing new chemotherapeutic agents and conducting site direct mutagenesis experiments.

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.

Degradation of Penicillin-Binding Protein 2′ in Methicillin-Resistant Staphylococcus aureus

Chemotherapy ◽  
1995 ◽  
Vol 41 (3) ◽  
pp. 172-177 ◽  
Author(s):  
Y. Sumita ◽  
M. Fukasawa ◽  
S. Mitsuhashi ◽  
M. Inoue
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant

scholarly journals Genetic Diversity amongStaphylococcus aureusIsolates Showing Oxacillin and/or Cefoxitin Resistance Not Linked to the Presence ofmecGenes

2018 ◽  
Vol 62 (7) ◽  
pp. e00091-18 ◽  
Author(s):  
M. Angeles Argudín ◽  
S. Roisin ◽  
L. Nienhaus ◽  
M. Dodémont ◽  
R. de Mendonça ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Staphylococcus Aureus ◽  
Binding Protein ◽  
Missense Mutations ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTMethicillin-resistantStaphylococcus aureusisolates lackingmecgenes (n= 32), collected from Belgian hospitals, were characterized for their β-lactamase production and the presence of mutations inpbpgenes, thepbp4promoter, and genes involved in penicillin-binding protein 4 overproduction (gdpPandyjbH). Twelve isolates were β-lactamase hyperproducers (BHPs), while 12 non-BHP isolates might produce an incomplete GdpP protein. Most isolates showed nucleotide missense mutations inpbpgenes. A few isolates also showed mutations in thepbp4promoter.

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