scholarly journals Characterization of penicillin-binding protein 2 of Staphylococcus aureus: deacylation reaction and identification of two penicillin-binding peptides.

1992 ◽  
Vol 36 (3) ◽  
pp. 656-661 ◽  
Author(s):  
H F Chambers ◽  
C Miick
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Binding Peptides

scholarly journals Microtiter Plate-Based Assay for Inhibitors of Penicillin-Binding Protein 2a from Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (6) ◽  
pp. 2783-2787 ◽  
Author(s):  
Sudheer Bobba ◽  
V. K. Chaithanya Ponnaluri ◽  
Mridul Mukherji ◽  
William G. Gutheil
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Protein ◽  
Binding Constants ◽  
Public Health Problem ◽  
Microtiter Plate ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant ◽  
Content Type ◽  
High Level

ABSTRACTPenicillin-binding protein 2a (PBP2a), the molecular determinant for high-level β-lactam resistance in methicillin-resistantStaphylococcus aureus(MRSA), is intrinsically resistant to most β-lactam antibiotics. The development and characterization of new inhibitors targeting PBP2a would benefit from an effective and convenient assay for inhibitor binding. This study was directed toward the development of a fluorescently detected β-lactam binding assay for PBP2a from MRSA. Biotinylated ampicillin and biotinylated cephalexin were tested as tagging reagents for fluorescence detection by using a streptavidin-horseradish peroxidase conjugate. Both bound surprisingly well to PBP2a, with binding constants of 1.6 ± 0.4 μM and 13.6 ± 0.8 μM, respectively. Two forms of the assay were developed, a one-step direct competition form of the assay and a two-step indirect competition form of the assay, and both forms of the assay gave comparable results. This assay was then used to characterize PBP2a binding to ceftobiprole, which gave results consistent with previous studies of ceftobiprole-PBP2a binding. This assay was also demonstrated for screening for PBP2a inhibitors by screening a set of 13 randomly selected β-lactams for PBP2a inhibition at 750 μM. Meropenem was observed to give substantial inhibition in this screen, and a follow-up titration experiment determined its apparentKito be 480 ± 70 μM. The availability of convenient and sensitive microtiter-plate based assays for the screening and characterization of PBP2a inhibitors is expected to facilitate the discovery and development of new PBP2a inhibitors for use in combating the serious public health problem posed by MRSA.

scholarly journals Studi Interaksi Molekuler Aktivitas Antimikroba Peptida Bioaktif terhadap Staphylococcus aureus Secara In silico

2020 ◽  
Vol 7 (2) ◽  
pp. 93
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Binding Protein ◽  
Pelteobagrus Fulvidraco ◽  
Penicillin Binding Protein ◽  
Discovery Studio

Pendahuluan: Lendir kulit ikan lele kuning (Pelteobagrus fulvidraco), mengandung peptida bioaktif dan banyak dimanfaatkan dalam pengobatan berbagai penyakit karena memiliki aktivitas biologis, diantaranya sebagai antimikroba. Beberapa peptida bioaktif tersebut, antara lain pelteobagrin, myxinidin, pleurocidin, dan pardaxin-P1 dan telah terbukti mampu menghambat Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus. Tujuan: Penelitian ini bertujuan untuk mengidentifikasi aktivitas antimikroba molekul peptida bioaktif secara in silico terhadap makromolekul Penicillin-Binding Protein 3 (PBP3) dari Staphylococcus aureus dan interaksi peptida bioaktif tersebut yang terlibat dalam mekanisme aksi antimikroba. Metode: Sekuensing peptida bioaktif terlebih dahulu dilakukan pemodelan ke dalam bentuk konformasi 3D menggunakan software PEP-FOLD. Konformasi terbaik hasil pemodelan dipilih untuk kemudian dilakukan studi penambatan molekuler terhadap makromolekul dari Staphylococcus aureus menggunakan software PatchDock. Interaksi molekuler yang terbentuk selanjutnya diidentifikasi lebih lanjut menggunakan software BIOVIA Discovery Studio 2020. Hasil: Berdasarkan hasil penambatan molekuler menunjukkan bahwa peptida bioaktif myxinidin memiliki afinitas paling baik dengan ACE score −2497,26 kJ/mol. Kesimpulan: Peptida bioaktif lendir kulit ikan lele kuning (Pelteobagrus fulvidraco) dapat dipertimbangkan sebagai kandidat antimikroba alami.

scholarly journals Identification of Penicillin Binding Protein 4 (PBP4) as a critical factor for Staphylococcus aureus bone invasion during osteomyelitis in mice

2020 ◽  
Vol 16 (10) ◽  
pp. e1008988 ◽  
Author(s):  
Elysia A. Masters ◽  
Karen L. de Mesy Bentley ◽  
Ann Lindley Gill ◽  
Stephanie P. Hao ◽  
Chad A. Galloway ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Protein ◽  
Critical Factor ◽  
Penicillin Binding Protein ◽  
Bone Invasion

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 Penicillin-Binding Protein 2 Is Essential for Expression of High-Level Vancomycin Resistance and Cell Wall Synthesis in Vancomycin- Resistant Staphylococcus aureus Carrying the Enterococcal vanA Gene Complex

2004 ◽  
Vol 48 (12) ◽  
pp. 4566-4573 ◽  
Author(s):  
Anatoly Severin ◽  
Shang Wei Wu ◽  
Keiko Tabei ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Binding Protein ◽  
Inducible Promoter ◽  
Protein Product ◽  
Vancomycin Resistance ◽  
Penicillin Binding Protein ◽  
Oxacillin Resistance ◽  
Vancomycin Resistant ◽  
High Level

ABSTRACT A combination of biochemical and genetic experiments were performed in order to better understand the mechanism of expression of high-level vancomycin resistance in Staphylococcus aureus. The transcription of pbp2 of the highly vancomycin- and oxacillin-resistant strain COLVA200 and its mutant derivative with inactivated mecA were put under the control of an inducible promoter, and the dependence of oxacillin and vancomycin resistance and cell wall composition on the concentration of the isopropyl-β-d-thiogalactopyranoside inducer was determined. The results indicate that mecA—the genetic determinant of oxacillin resistance—while essential for oxacillin resistance, is not involved with the expression of vancomycin resistance. Penicillin binding protein 2A, the protein product of mecA, appears to be unable to utilize the depsipeptide cell wall precursor produced in the vancomycin-resistant cells for transpeptidation. The key penicillin binding protein essential for vancomycin resistance and for the synthesis of the abnormally structured cell walls characteristic of vancomycin-resistant S. aureus (A. Severin, K. Tabei, F. Tenover, M. Chung, N. Clarke, and A. Tomasz, J. Biol. Chem. 279:3398-3407, 2004) is penicillin binding protein 2.

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