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Updated: Jul 8, 2026
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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
Published on: July 7, 2020
Extended-spectrum beta-lactamases and the permeability barrier
1Service of Microbiology, University Hospital Marqués de Valdecilla, Santander, Spain. lmartinez@humv.es
Summary
Loss of porins, protein channels in Gram-negative bacteria, significantly enhances antimicrobial resistance. This impacts the effectiveness of antibiotics like cephalosporins and carbapenems, particularly in resistant bacterial strains.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Gram-negative bacteria possess an outer membrane acting as a barrier to hydrophilic compounds.
- Porins, water-filled protein channels in the outer membrane, are crucial for antibiotic entry.
- Loss of porins is a key mechanism contributing to antimicrobial resistance, especially in conjunction with other resistance factors.
Purpose of the Study:
- To investigate the role of porin expression in antimicrobial resistance in clinical isolates of *Klebsiella pneumoniae*.
- To understand the impact of specific porin loss (OmpK35 and OmpK36) on resistance to various antibiotic classes.
Main Methods:
- Analysis of porin expression in clinical isolates of *Klebsiella pneumoniae*.
- Phenotypic characterization of antibiotic susceptibility in strains with altered porin expression.
- Correlation of porin deficiency with resistance to beta-lactams and fluoroquinolones.
Main Results:
- Many extended-spectrum beta-lactamase (ESBL)-producing *K. pneumoniae* clinical isolates lack the OmpK35 porin.
- Loss of both OmpK35 and OmpK36 porins in ESBL-producing *K. pneumoniae* leads to resistance against cefoxitin.
- Deficiency in OmpK35/OmpK36 results in increased resistance to expanded-spectrum cephalosporins and decreased susceptibility to carbapenems (e.g., ertapenem) and fluoroquinolones.
Conclusions:
- Porin deficiency is a critical factor in the antimicrobial resistance of ESBL-producing *Klebsiella pneumoniae*.
- Loss of major porins significantly compromises the efficacy of a broad range of antibiotics, including beta-lactams and fluoroquinolones.
- Targeting porin expression could be a strategy to overcome antimicrobial resistance in Gram-negative pathogens.
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