P36 Chromosomal mutation, other than mec operon, promotes high-level oxacillin resistance in OS-MRSA

2013 ◽  
Vol 42 ◽  
pp. S52-S53
Author(s):  
L. Cui ◽  
H. Matsui ◽  
T. Nakae ◽  
H. Hanaki
Keyword(s):  
Chromosomal Mutation ◽  
Oxacillin Resistance ◽  
High Level

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.

scholarly journals Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” (fem) Mutants by Induction of the Stringent Stress Response

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Choon Keun Kim ◽  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Stress Response ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Penicillin Binding Protein ◽  
Methicillin Resistant ◽  
Content Type ◽  
Oxacillin Resistance ◽  
Response Recovery ◽  
High Level

ABSTRACT Studies with methicillin-resistant Staphylococcus aureus (MRSA) strain COL have shown that the optimal resistance phenotype requires not only mecA but also a large number of “auxiliary genes” identified by Tn551 mutagenesis. The majority of auxiliary mutants showed greatly increased levels of oxacillin resistance when grown in the presence of sub-MICs of mupirocin, suggesting that the mechanism of reduced resistance in the auxiliary mutants involved the interruption of a stringent stress response, causing reduced production of penicillin-binding protein 2A (PBP 2A).

scholarly journals Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001

2004 ◽  
Vol 48 (6) ◽  
pp. 2049-2055 ◽  
Author(s):  
K. J. Christiansen ◽  
J. M. Bell ◽  
J. D. Turnidge ◽  
R. N. Jones
Keyword(s):  
Partial Correlation ◽  
Antimicrobial Activities ◽  
Asia Pacific ◽  
Pacific Region ◽  
Asia Pacific Region ◽  
Oxacillin Resistance ◽  
Wide Range ◽  
Ciprofloxacin Resistance ◽  
High Level ◽  
Level Resistance

ABSTRACT Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 μg/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 μg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 μg/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 μg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.

scholarly journals 194. Antimicrobial Susceptibility Data of Staphylococcus lugdunensis After the Implementation of Rapid Molecular Blood Culture Diagnostics (Verigene® Gram-Positive Blood Culture Nucleic Acid Test)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S204-S205
Author(s):  
Kristin Constance ◽  
Alauna Hunt ◽  
Sam Karimaghaei ◽  
Juliet Chijioke ◽  
Violeta Chavez ◽  
...  
Keyword(s):  
Blood Culture ◽  
Multiplex Pcr ◽  
Large Scale ◽  
Meca Gene ◽  
Coagulase Negative Staphylococci ◽  
Hospital System ◽  
Susceptibility Data ◽  
Oxacillin Resistance ◽  
High Level ◽  
Resistance Rates

Abstract Background S. lugdunensis is a coagulase negative staphylococci (CoNS) demonstrating high level pathogenicity. In contrast to other CoNS, S. lugdunensis (SL) remains susceptible to most antibiotics. Prior to the implementation of Verigene®, SL was identified by provider request only. We sought to describe the susceptibility data of SL isolated from blood culture after the implementation of multiplex PCR, as well as to determine the correlation of the mecA gene provided by Verigene® and oxacillin resistance. Methods Retrospective review of all blood culture isolates positive for SL from two major hospital systems, Memorial Hermann Hospital System (14 hospitals) and HarrisHealth System (two acute care hospitals) identified on Verigene® PCR. Multiple isolates detected from the same patients were excluded from this analysis. Memorial Hermann utilized Microscan®, and HarrisHealth utilized BD Phoenix® for susceptibility testing. Results Between 2017 – 2021, 157 patients were identified with SL positive blood cultures. Of them, 141 isolates had susceptibility data collected, which is summarized in table 1. Resistance rates were highest amongst clindamycin 97/141 (68.8 %) susceptible, erythromycin 98/141 (69.5%) susceptible, and oxacillin 120/141 (85.1%) susceptible. 127/141 (90.1%) of isolates were tested for mecA on Verigene®. 13 of 21 oxacillin resistant isolates were from pure culture, of these isolates, none had mecA detected. Conclusion In our study, clindamycin and erythromycin demonstrated similar susceptibility compared to prior studies in the literature, however oxacillin susceptibility rate was lower than expected at 85.1%, compared to 95.3% in a prior large-scale United States based study in 2017. Absence of mecA gene detection on multiplex PCR did not correlate with oxacillin susceptibility suggesting that oxacillin susceptibility cannot be accurately predicted by the use of multiplex PCR systems, such as Verigene®, as demonstrated in Table 2. Our study also suggested that increased prevalence of oxacillin resistant SL isolates may be emerging. Disclosures All Authors: No reported disclosures

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

Advances in Stem Instrumentation for Biology

1990 ◽  
Vol 48 (1) ◽  
pp. 362-363
Author(s):  
J. S. Wall
Keyword(s):  
Scanning Transmission Electron Microscope ◽  
Carbon Films ◽  
Specimen Preparation ◽  
Material Deposition ◽  
Active User ◽  
Percent Improvement ◽  
Scanning Transmission ◽  
The Moment ◽  
Film Substrate ◽  
High Level

The forte of the Scanning transmission Electron Microscope (STEM) is high resolution imaging with high contrast on thin specimens, as demonstrated by visualization of single heavy atoms. of equal importance for biology is the efficient utilization of all available signals, permitting low dose imaging of unstained single molecules such as DNA.Our work at Brookhaven has concentrated on: 1) design and construction of instruments optimized for a narrow range of biological applications and 2) use of such instruments in a very active user/collaborator program. Therefore our program is highly interactive with a strong emphasis on producing results which are interpretable with a high level of confidence.The major challenge we face at the moment is specimen preparation. The resolution of the STEM is better than 2.5 A, but measurements of resolution vs. dose level off at a resolution of 20 A at a dose of 10 el/A2 on a well-behaved biological specimen such as TMV (tobacco mosaic virus). To track down this problem we are examining all aspects of specimen preparation: purification of biological material, deposition on the thin film substrate, washing, fast freezing and freeze drying. As we attempt to improve our equipment/technique, we use image analysis of TMV internal controls included in all STEM samples as a monitor sensitive enough to detect even a few percent improvement. For delicate specimens, carbon films can be very harsh-leading to disruption of the sample. Therefore we are developing conducting polymer films as alternative substrates, as described elsewhere in these Proceedings. For specimen preparation studies, we have identified (from our user/collaborator program ) a variety of “canary” specimens, each uniquely sensitive to one particular aspect of sample preparation, so we can attempt to separate the variables involved.

A Questionnaire Survey of Current Rehabilitation Practices for Adults With Normal Hearing Sensitivity Who Experience Auditory Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 738-761
Author(s):  
Tess K. Koerner ◽  
Melissa A. Papesh ◽  
Frederick J. Gallun
Keyword(s):  
Hearing Aids ◽  
Questionnaire Survey ◽  
Patient Population ◽  
Clinical Care ◽  
Normal Hearing ◽  
Auditory Training ◽  
Training Methods ◽  
Hearing Sensitivity ◽  
Considerable Benefit ◽  
High Level

Purpose A questionnaire survey was conducted to collect information from clinical audiologists about rehabilitation options for adult patients who report significant auditory difficulties despite having normal or near-normal hearing sensitivity. This work aimed to provide more information about what audiologists are currently doing in the clinic to manage auditory difficulties in this patient population and their views on the efficacy of recommended rehabilitation methods. Method A questionnaire survey containing multiple-choice and open-ended questions was developed and disseminated online. Invitations to participate were delivered via e-mail listservs and through business cards provided at annual audiology conferences. All responses were anonymous at the time of data collection. Results Responses were collected from 209 participants. The majority of participants reported seeing at least one normal-hearing patient per month who reported significant communication difficulties. However, few respondents indicated that their location had specific protocols for the treatment of these patients. Counseling was reported as the most frequent rehabilitation method, but results revealed that audiologists across various work settings are also successfully starting to fit patients with mild-gain hearing aids. Responses indicated that patient compliance with computer-based auditory training methods was regarded as low, with patients generally preferring device-based rehabilitation options. Conclusions Results from this questionnaire survey strongly suggest that audiologists frequently see normal-hearing patients who report auditory difficulties, but that few clinicians are equipped with established protocols for diagnosis and management. While many feel that mild-gain hearing aids provide considerable benefit for these patients, very little research has been conducted to date to support the use of hearing aids or other rehabilitation options for this unique patient population. This study reveals the critical need for additional research to establish evidence-based practice guidelines that will empower clinicians to provide a high level of clinical care and effective rehabilitation strategies to these patients.

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