Bacterial conjugation machinery in Gram-negative pathogen ()

Bacterial conjugation machinery in Gram-negative pathogen Overview

The **bacterial conjugation machinery in Gram-negative pathogens** is a multiprotein system that mediates horizontal gene transfer via direct cell-to-cell contact, functioning as the primary mechanism by which plasmid DNA—including antibiotic resistance, virulence, and metabolic genes—is disseminated within and between bacterial populations[1][5][3]. This process is universally conserved among Gram-negative bacteria, with the machinery encoded either on conjugative plasmids or integrative conjugative elements. The system comprises key complexes such as the **relaxosome** (responsible for site-specific plasmid DNA cleavage and processing), the **Type IV coupling protein (T4CP, a hexameric ATPase transporter)**, and the **Type IV secretion system (T4SS)** which constructs the conjugative pilus necessary for DNA transfer[3][5][6]. Disruption of this machinery represents a novel and increasingly studied therapeutic approach for controlling the spread of antibiotic resistance, though no clinically approved conjugation inhibitors are available yet[6][8]. The machinery's involvement in infection biology, resistance transmission, and potential for targeting by engineered antimicrobials (e.g., CRISPR-delivery via conjugation) makes it a central focus in infectious disease and antimicrobial resistance research[4][7][2].

Mechanism of Action

Inhibition of ATPase activity in Type IV coupling protein (T4CP) blocks DNA transfer[8][6] Blocking pilus assembly or function prevents cell contact and DNA transport[8] Disrupting relaxosome activity or DNA processing machinery impedes plasmid transfer[3][5]

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers