Target intelligence / Profile preview

Gram-negative bacterial pathogens (GNB)

Target
GNB
Molecular classification
Prokaryotic organism, Bacterial pathogen
01

Overview

Gram-negative bacterial pathogens are a diverse group of bacteria characterized by a complex cell envelope consisting of an inner cytoplasmic membrane, a thin peptidoglycan cell wall, and a unique outer membrane containing lipopolysaccharides (LPS) (Silhavy et al., 2010, Cold Spring Harb Perspect Biol). This outer membrane acts as a selective permeability barrier that contributes to intrinsic resistance against many antibiotics, making these organisms a primary focus of drug development (WHO, 2024). Key pathogens in this group include Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, which are responsible for a wide range of clinical conditions such as sepsis, pneumonia, and urinary tract infections (CDC, 2019). The clinical management of these infections is increasingly challenged by the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains, particularly carbapenem-resistant Enterobacteriaceae (CRE). Current therapeutic interventions target various essential bacterial components, including the cell wall, ribosomes, and nucleic acid synthesis machinery. Developing novel agents that can bypass or inhibit the efflux pumps and low-permeability barriers of Gram-negative bacteria remains a critical priority in infectious disease research.

Other names
Gram-negative bacteriaGNBGram-negativesGram-negative organisms
02

Mechanism of action

Inhibition of peptidoglycan synthesis (beta-lactams), disruption of the outer membrane (polymyxins), inhibition of the 30S/50S ribosomal subunits (aminoglycosides, tetracyclines), and inhibition of DNA gyrase/topoisomerase IV (fluoroquinolones).

03

Biological functions

Bacterial metabolismCell wall synthesisProtein synthesisPathogenesisVirulence factor secretionAntibiotic resistance
04

Disease associations

InfectionSepsisPneumoniaUrinary tract infectionIntra-abdominal infectionMeningitisHealthcare-associated infections
05

Safety considerations

Antimicrobial resistance (AMR) developmentNephrotoxicity (e.g., aminoglycosides, polymyxins)Ototoxicity (e.g., aminoglycosides)Clostridioides difficile infection (CDI) due to microbiome disruptionJarisch-Herxheimer reactionHypersensitivity reactions
06

Interacting drugs

Meropenem

8 more in the full profile.

07

Biomarkers

Gram stainBacterial culture and sensitivityProcalcitonin (PCT)C-reactive protein (CRP)Polymerase chain reaction (PCR) for pathogen-specific DNAMatrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry

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