Outer Membrane Porins and Antibiotic Resistance Mechanisms in Gram-Negative Bacteria

Gram-negative bacteria possess an asymmetric cell envelope in which the outer membrane serves as a selective barrier to external agents, including many antibiotics. Embedded within this bilayer are outer membrane porins, water-filled channels that permit the passive diffusion of small hydrophilic molecules. Modulation of porin expression or structure, in conjunction with other resistance strategies such as production of β-lactamases, carbapenemases and activation of efflux pumps, can markedly reduce intracellular drug accumulation. Loss or mutation of major porins (for example OmpF/C in Escherichia coli and OmpK35/36 in Klebsiella pneumoniae) diminishes uptake of β-lactams, carbapenems and other hydrophilic antibiotics, often raising minimum inhibitory concentrations (MICs) above therapeutic levels. At the same time, coordinated regulation by transcriptional regulators (such as OmpR) and compensatory adjustments in membrane integrity or nutrient acquisition pathways allow pathogenic strains to maintain fitness. The interplay between porin alteration, enzymatic degradation and active efflux underpins the multifaceted resistance phenotypes observed in clinical isolates, driving the emergence and global dissemination of multidrug-resistant Gram-negative pathogens.

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Outer Membrane Porins and Antibiotic Resistance Mechanisms in Gram-Negative Bacteria publication trend

The graph below shows the total number of articles in outer membrane porins and antibiotic resistance mechanisms in gram-negative bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Porin: An outer membrane protein forming a channel that allows passive diffusion of small hydrophilic molecules into Gram-negative bacteria.

β-lactamase: An enzyme produced by bacteria that hydrolyses the β-lactam ring of penicillins and cephalosporins, rendering these antibiotics ineffective.

Carbapenemase: A subclass of β-lactamases capable of degrading carbapenem antibiotics, often associated with high-level resistance in clinical isolates.

Efflux pump: A transporter protein complex that actively expels antibiotics and other toxic compounds from the bacterial cell, reducing intracellular drug concentration.

Minimum inhibitory concentration (MIC): The lowest concentration of an antibiotic that prevents visible growth of a bacterium under defined conditions.

References

1. Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35. Journal of Biomedical Science (2023).
2. Gut microbiota-derived butyrate selectively interferes with growth of carbapenem-resistant Escherichia coli based on their resistance mechanism. Gut Microbes (2024).
3. Investigation on the mechanisms of carbapenem resistance among the non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology (2024).