scholarly journals Discrimination of methicillin-resistant Staphylococcus aureus from methicillin-susceptible Staphylococcus aureus or coagulase-negative staphylococci by detection of penicillin-binding protein 2 and penicillin-binding protein 2′ using a bioluminescent enzyme immunoassay

2013 ◽  
Vol 388 (1-2) ◽  
pp. 40-45 ◽  
Author(s):  
Kazuki Shiga ◽  
Keiko Gomi ◽  
Motoi Nishimura ◽  
Masaharu Watanabe ◽  
Fumio Nomura ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Enzyme Immunoassay ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant

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 In Vitro Activities of Noveltrans-3,5-Disubstituted Pyrrolidinylthio-1β-Methylcarbapenems with Potent Activities against Methicillin-Resistant Staphylococcus aureus andPseudomonas aeruginosa

2000 ◽  
Vol 44 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Rie Nagano ◽  
Kaneyoshi Shibata ◽  
Yuka Adachi ◽  
Hideaki Imamura ◽  
Terutaka Hashizume ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Side Chain ◽  
The Novel ◽  
Good Activity ◽  
Penicillin Binding Protein ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
The Family

ABSTRACT The in vitro activities of the novel 1β-methylcarbapenems J-111,225, J-114,870, and J-114,871, which have a structurally unique side chain that consists of a trans-3,5-disubstituted 5-arylpyrrolidin-3-ylthio moiety at the C-2 position, were compared with those of reference antibiotics. Among isolates of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS), 90% were inhibited by J-111,347 (prototype), J-111,225, J-114,870, and J-114,871 at concentrations of 2, 4, 4, and 4 μg/ml (MICs at which 90% of isolates are inhibited [MIC90s]), respectively, indicating that these agents were 32- to 64-fold more potent than imipenem, which has an MIC90 of 128 μg/ml. Although these drugs were less active in vitro than vancomycin, which had MIC90s of 1 and 2 μg/ml for MRSA and MRCoNS, respectively, the new carbapenems displayed better killing kinetics than vancomycin. The potent anti-MRSA activity was ascribed to the excellent affinities of the new carbapenems for penicillin-binding protein 2a of MRSA. Since the new carbapenems also exhibited good activity against gram-positive and -negative bacteria including clinically important pathogens such as penicillin-resistantStreptococcus pneumoniae, Haemophilus influenzae, members of the family Enterobacteriaceae,Pseudomonas aeruginosa, and Clostridium difficile, as well as MRSA, the novel carbapenems are worthy of further evaluation.

scholarly journals Specific interaction between beta-lactams and soluble penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: development of a chromogenic assay.

1996 ◽  
Vol 40 (9) ◽  
pp. 2075-2079 ◽  
Author(s):  
S Roychoudhury ◽  
R E Kaiser ◽  
D N Brems ◽  
W K Yeh
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Methicillin Resistant ◽  
Chromogenic Assay ◽  
Enzymatic Acylation

We investigated the enzymatic acylation of penicillin-binding protein 2a (PBP 2a) from methicillin-resistant Staphylococcus aureus by beta-lactams. Using a purified, soluble form of the protein (PBP 2a'), we observed beta-lactam-induced in vitro precipitation following first-order kinetics with respect to protein concentration. We used electrospray mass ionization spectrometry to show that the protein precipitate predominantly contained PBP 2a', with the beta-lactam bound to it in a 1:1 molar ratio. Using nitrocefin, a chromogenic beta-lactam, we confirmed the correlation between PBP 2a' precipitation and its beta-lactam-dependent enzymatic acylation by monitoring the absorbance associated with the precipitate. Finally, dissolving the precipitate in urea, we developed a simple in vitro chromogenic assay to monitor beta-lactam-dependent enzymatic acylation of PBP 2a'. This assay represents a significant improvement over the traditional radioactive penicillin-binding assay.

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