Sub-minimum inhibitory concentrations of ceftazidime inhibit Pseudomonas aeruginosa biofilm formation
Satoshi Otani1, Kazufumi Hiramatsu2, Kazuhiko Hashinaga1
1Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
Abstract:
Pseudomonas aeruginosa exhibits the biofilm mode of growth and causes chronic as well as acute infections in humans. Several reports have shown that the treatments with sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial agents influence biofilm formation by P. aeruginosa. The antibiotic ceftazidime (CAZ) is used to treat P. aeruginosa infections, but few studies have examined the effects of β-lactams on biofilm formation by P. aeruginosa. In this study, we investigated the role of sub-MICs of CAZ in the formation of P. aeruginosa biofilms. 1/4 × MIC CAZ reduced the biofilm volume of P. aeruginosa PAO1, as quantified by crystal violet staining. The formation of P. aeruginosa PAO1 biofilms treated with 1/4 × MIC CAZ were observed by confocal laser scanning microscopy. They were more heterogeneous than the PAO1 biofilms without CAZ treatment. Furthermore, sub-MICs of CAZ inhibited the twitching motility, which played an important role in mature biofilm formation. 1/4 × MIC CAZ also reduced the gene expressions of lecA, lecB, pel and psl, which mediate the adhesion and polysaccharide matrix synthesis of P. aeruginosa. These effects suggest that sub-MICs of CAZ may affect a number of stages of biofilm formation. Investigating the effects of sub-MIC antibiotics on targeted bacterial biofilm may lead to the development of future antibiotic treatment modalities.
Insights
Low concentrations of ceftazidime (CAZ) reduce Pseudomonas aeruginosa biofilm formation by affecting motility and matrix production. This study explores sub-inhibitory antibiotic concentrations for potential new anti-biofilm strategies.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Pseudomonas aeruginosa is a significant human pathogen causing acute and chronic infections.
- Biofilm formation is a key virulence factor for P. aeruginosa.
- Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics can modulate bacterial behavior, including biofilm development.
Purpose of the Study:
- To investigate the effects of sub-MICs of ceftazidime (CAZ) on P. aeruginosa biofilm formation.
- To elucidate the mechanisms by which sub-MIC CAZ influences biofilm structure and development.
Main Methods:
- Quantitative assessment of biofilm volume using crystal violet staining.
- Visualization of biofilm architecture via confocal laser scanning microscopy.
- Analysis of gene expression for adhesion and matrix synthesis genes (e.g., lecA, lecB, pel, psl).
- Assessment of twitching motility.
Main Results:
- A 1/4 × MIC of CAZ significantly reduced P. aeruginosa PAO1 biofilm volume.
- CAZ treatment resulted in more heterogeneous biofilm structures.
- Sub-MIC CAZ inhibited twitching motility, crucial for mature biofilm formation.
- Gene expression of adhesion and polysaccharide matrix components (lec A, lec B, pel, psl) was downregulated by sub-MIC CAZ.
Conclusions:
- Sub-MIC concentrations of ceftazidime impact multiple stages of P. aeruginosa biofilm formation.
- CAZ at sub-MIC levels affects biofilm structure, motility, and matrix production.
- Targeting bacterial biofilms with sub-inhibitory antibiotic concentrations presents a potential avenue for novel therapeutic strategies against P. aeruginosa infections.
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