Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of , has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity and confer high-level resistance to β-lactam antibiotics, such as ceftobiprole and ceftaroline.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444179PMC
http://dx.doi.org/10.1128/AAC.02727-16DOI Listing

Publication Analysis

Top Keywords

high-level resistance
12
β-lactam antibiotics
12
penicillin-binding protein
12
pbp4
8
protein pbp4
8
resistance β-lactam
8
pbp4 compared
8
highly cross-linked
8
cross-linked cell
8
cell wall
8

Similar Publications

Enterococcus species, natural inhabitants of the human gut, have become major causes of life-threatening bloodstream infections (BSIs) and the third most frequent cause of hospital-acquired bacteremia. The rise of high-level gentamicin resistance (HLGR) in enterococcal isolates complicates treatment and revives bacteriophage therapy. This study isolated and identified forty E.

View Article and Find Full Text PDF
Article Synopsis
  • Pseudomonas aeruginosa is problematic in healthcare due to its high antibiotic resistance, highlighting the need for new antimicrobial solutions.
  • A study focused on isolating a new bacteriocin from Enterococcus faecium found in stool samples, which showed promise against multidrug-resistant P. aeruginosa.
  • The purified bacteriocin, enterocin GH, demonstrated significant antibacterial and antibiofilm activity against P. aeruginosa, outperforming controls in laboratory tests.
View Article and Find Full Text PDF

Carbapenem resistant Acinetobacter baumannii has evolved as the most troublesome microorganism with multiple virulence factors. Biofilm formation, porins, micronutrient capturing mechanism and quorum sensing, provide protection against desiccation, host-pathogen killing and enhance its persistence. The conservation of these factors between colonizing and pathogenic carbapenem resistant A.

View Article and Find Full Text PDF

Amorphous solid dispersion (ASD) technology is often used as a promising strategy to improve the solubility of active pharmaceutical ingredients (APIs). ASDs allow APIs to be dispersed at the molecular level in a polymer carrier, destroying the crystalline structure of the APIs and, thanks to the polymer, providing long-term supersaturation in solution. However, stability issues are an obstacle to the development of new medications with ASD.

View Article and Find Full Text PDF

Copper matrix composites (Cu-MCs) have garnered significant attention due to their exceptional electrical, wear-resistant, and mechanical properties. Among them, AlO/Cu composites, reinforced with AlO, are a focal point in the field of high-strength, high-conductivity copper alloys, owing to their high strength, excellent electrical conductivity, and superior resistance to high-temperature softening. Cold deformation is an effective method for enhancing the mechanical properties of AlO/Cu composites.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!