scholarly journals Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance

FEBS Journal ◽  
2016 ◽  
Vol 283 (12) ◽  
pp. 2206-2218 ◽  
Author(s):  
Ekaterina V. Filippova ◽  
Karen J. Kieser ◽  
Chi-Hao Luan ◽  
Zdzislaw Wawrzak ◽  
Olga Kiryukhina ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Crystal Structures ◽  
Binding Protein ◽  
Penicillin Binding Protein

scholarly journals Prevalence, Antibiogram and Molecular Characterization of Comunity-Acquired Methicillin-Resistant Staphylococcus Aureus in AWKA, Anambra Nigeria

2016 ◽  
Vol 10 (1) ◽  
pp. 211-221 ◽  
Author(s):  
Blessing Ike ◽  
Malachy C. Ugwu ◽  
Moses N. Ikegbunam ◽  
David Nwobodo ◽  
Chika Ejikeugwu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Binding Protein ◽  
Meca Gene ◽  
Latex Agglutination ◽  
Diffusion Method ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Penicillin Binding Protein ◽  
Carriage Rate ◽  
Molecular Features

Objectives:This study evaluated the prevalence, antibiogram and molecular features of CA-MRSA in Awka, Nigeria.Methods:Confirmation of MRSA was done by testing resistance to oxacillin (1µg), cloxacillin (5µg) and cefoxitin(30µg) on sterile Mueller Hinton agar supplemented with 4% sodium chloride. The MRSA strains were subjected to antimicrobial susceptibility testing using Kirby-Bauer disc diffusion method. Minimum inhibitory concentration was determined using agar dilution method. Penicillin binding protein 2a was detected through rapid latex agglutination assay while mecA gene was detected by polymerase chain reaction. A total of 142S. aureusisolates were obtained from 261 samples sourced from Staff, students and fomites of the Faculty of Pharmaceutical SciencesResult:The overall prevalence of MRSA was 22.6%. The carriage rate was higher in females (56.5%) than male (43.5%) and was highest in individuals of 20-30 years of age (57.65%). The MIC of the oxacillin sodium salt ranged from 4-32 μg/ml. The multi-antibiotic resistance indices show that 53.4% had Multiple Antibiotic Resistance Indexing (MARI) higher than 0.2. Penicillin binding protein 2a was detected in 8.4% of MRSA isolates, all from nasal carriage while mecA gene was detected in 5 of isolates.Conclusion:This study showed a very high prevalence of MRSA carriage among studied subjects.

scholarly journals Crystal structures of penicillin-binding protein 3 in complexes with azlocillin and cefoperazone in both acylated and deacylated forms

FEBS Letters ◽  
2016 ◽  
Vol 590 (2) ◽  
pp. 288-297 ◽  
Author(s):  
Jingshan Ren ◽  
Joanne E. Nettleship ◽  
Alexandra Males ◽  
David I. Stuart ◽  
Raymond J. Owens
Keyword(s):  
Crystal Structures ◽  
Binding Protein ◽  
Penicillin Binding Protein

scholarly journals On-Chip Isoniazid Exposure of Mycobacterium smegmatis Penicillin-Binding Protein (PBP) Mutant Using Time-Lapse Fluorescent Microscopy

Micromachines ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 561
Author(s):  
Meltem Elitas
Keyword(s):  
Antibiotic Resistance ◽  
Single Cell ◽  
Mycobacterium Smegmatis ◽  
Single Cell Analysis ◽  
Binding Protein ◽  
Cell Analysis ◽  
Penicillin Binding Protein ◽  
Intact Cells ◽  
The Impact ◽  
Mutant Cells

Antibiotic resistance has been one of the biggest threats to global health. Despite the available prevention and control strategies and efforts in developing new antibiotics, the need remains for effective approaches against antibiotic resistance. Efficient strategies to cope with antimicrobial resistance require a quantitative and deeper understanding of microbial behavior, which can be obtained using different techniques to provide the missing pieces of the current antibiotic-resistance puzzle. Microfluidic-microscopy techniques are among the most promising methods that contribute modernization of traditional assays in microbiology. They provide monitoring and manipulation of cells at micro-scale volumes. Here, we combined population-level, culture-based assays with single-cell resolution, microfluidic-microscopy systems to investigate isoniazid response of Mycobacterium smegmatis penicillin-binding protein (PBP) mutant. This mutant exhibited normal growth in plain medium and sensitivity to stress responses when treated with thermal stress (45 °C), detergent stress (0.1% sodium dodecyl sulfate), acid stress (pH 4.5), and nutrient starvation (1XPBS). The impact of msm0031 transposon insertion on drug-mediated killing was determined for isoniazid (INH, 50 µg/mL), rifampicin (RIF, 200 µg/mL), ethionamide (ETH, 200 µg/mL), and ethambutol (EMB, 5 µg/mL). The PBP mutant demonstrated remarkable isoniazid-killing phenotype in batch culture. Therefore, we hypothesized that single-cell analysis will show increased lysis kinetics and fewer intact cells after drug treatment. However, the single-cell analysis data showed that upon isoniazid exposure, the percentage of the intact PBP mutant cells was 24%, while the percentage of the intact wild-type cells was 4.6%. The PBP mutant cells exhibited decreased cell-lysis profile. Therefore, the traditional culture-based assays were not sufficient to provide insights about the subpopulation of viable but non-culture cells. Consequently, we need more adequate tools to be able to comprehend and fight the antibiotic resistance of bacteria.

scholarly journals Crystal Structures of Penicillin-Binding Protein D2 fromListeria monocytogenesand Structural Basis for Antibiotic Specificity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Jae-Hee Jeong ◽  
Hyung Jin Cha ◽  
Yeon-Gil Kim
Keyword(s):  
Crystal Structures ◽  
Bacterial Infections ◽  
Binding Protein ◽  
Bacterial Pathogen ◽  
Penicillin G ◽  
Structural Basis ◽  
Side Chains ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Highly Correlated

ABSTRACTβ-Lactam antibiotics that inhibit penicillin-binding proteins (PBPs) have been widely used in the treatment of bacterial infections. However, the molecular basis underlying the different inhibitory potencies of β-lactams against specific PBPs is not fully understood. Here, we present the crystal structures of penicillin-binding protein D2 (PBPD2) fromListeria monocytogenes, a Gram-positive foodborne bacterial pathogen that causes listeriosis in humans. The acylated structures in complex with four antibiotics (penicillin G, ampicillin, cefotaxime, and cefuroxime) revealed that the β-lactam core structures were recognized by a common set of residues; however, the R1 side chains of each antibiotic participate in different interactions with PBPD2. In addition, the structural complementarities between the side chains of β-lactams and the enzyme were found to be highly correlated with the relative reactivities of penam or cephem antibiotics against PBPD2. Our study provides the structural basis for the inhibition of PBPD2 by clinically important β-lactam antibiotics that are commonly used in listeriosis treatment. Our findings imply that the modification of β-lactam side chains based on structural complementarity could be useful for the development of potent inhibitors against β-lactam-resistant PBPs.

Sign in / Sign up

Export Citation Format

Share Document