Trimethoprim, sulphamethoxazole, bacterial adhesion and polymorphonuclear leucocyte function

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Antibiotic resistance is a growing global health concern.
• Understanding sub-antimicrobial dose effects is crucial for novel therapeutic strategies.
• Bacterial adherence and host immune responses are key factors in infection pathogenesis.

Purpose of the Study:

• To investigate the impact of subinhibitory concentrations of trimethoprim and sulphamethoxazole on bacterial adherence and host immune cell function.
• To evaluate the effects of these antibiotics on the interaction between common uropathogens and human immune cells.

Main Methods:

• Culturing of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.
• Exposure to subinhibitory concentrations (1/4 Minimum Inhibitory Concentration) of trimethoprim, sulphamethoxazole, or their combination.
• Assessment of bacterial adherence to host cells.
• Evaluation of phagocytosis and bactericidal activity of polymorphonuclear leucocytes (PMNs).
• Analysis of the chemotactic response of human PMNs to bacterial filtrates.

Main Results:

• Subinhibitory antibiotic concentrations significantly reduced the adherence of all tested bacterial strains.
• No significant change in the number of phagocytosed bacteria was observed.
• A significant increase in the bactericidal activity of PMNs against pre-exposed bacteria was noted.
• Filtrates from bacteria grown with antibiotics enhanced the chemotactic response of human PMNs.

Conclusions:

• Subinhibitory antibiotic concentrations can modulate bacterial virulence factors, specifically reducing adherence.
• These antibiotic concentrations enhance the host immune response by increasing PMN bactericidal activity and chemotaxis.
• This suggests a potential role for sub-antimicrobial antibiotic dosing in modulating host-pathogen interactions and improving infection outcomes.