Antimicrobial and cytotoxic synergism of biocides and quorum-sensing inhibitors against uropathogenic Escherichia coli.

Background

Uropathogenic Escherichia coli (UPEC) are a primary cause of catheter-associated urinary tract infections (CAUTIs), often forming mature recalcitrant biofilms on the catheter surface. Anti-infective catheter coatings containing single biocides have been developed but display limited antimicrobial activity due to the selection of biocide-resistant bacterial populations. Furthermore, biocides often display cytotoxicity at concentrations required to eradicate biofilms, limiting their antiseptic potential. Quorum-sensing inhibitors (QSIs) provide a novel anti-infective approach to disrupt biofilm formation on the catheter surface and help prevent CAUTIs.

Aim

To evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bactericidal and biofilm eradication concentrations in parallel to assessing cytotoxicity in a bladder smooth muscle (BSM) cell line.

Methods

Checkerboard assays were performed to determine fractional inhibitory, bactericidal, and biofilm eradication concentrations of test combinations in UPEC and combined cytotoxic effects in BSM cells.

Findings

Synergistic antimicrobial activity was observed between polyhexamethylene biguanide, benzalkonium chloride or silver nitrate in combination with either cinnamaldehyde or furanone-C30 against UPEC biofilms. However, furanone-C30 was cytotoxic at concentrations below those required for even bacteriostatic activity. A dose-dependent cytotoxicity profile was observed for cinnamaldehyde when in combination with BAC, PHMB or silver nitrate. Both PHMB and silver nitrate displayed combined bacteriostatic and bactericidal activity below the half-maximum inhibitory concentration (IC₅₀). Triclosan in combination with both QSIs displayed antagonistic activity in both UPEC and BSM cells.

Conclusion

PHMB and silver in combination with cinnamaldehyde display synergistic antimicrobial activity in UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.

What is it about?

The study aimed to evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bactericidal, and biofilm eradication concentrations in parallel to assessing cytotoxicity in a bladder smooth muscle cell line. Checkerboard assays were performed to determine fractional inhibitory, bactericidal, and biofilm eradication concentrations of test combinations in UPEC and combined cytotoxic effects in BSM cells. Synergistic antimicrobial activity was observed between polyhexamethyline biguanide, benzalkonium chloride or silver nitrate in combination with either cinnamaldehyde or furanone-C30 against UPEC biofilms. PHMB and silver in combination with cinnamaldehyde display synergistic antimicrobial activity in UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.

Why is it important?

The research is important because it evaluates the combinatorial impact of biocides and quorum sensing inhibitors (QSIs) on antimicrobial activity against uropathogenic Escherichia coli (UPEC), which is a primary cause of catheter-associated urinary tract infections (CAUTIs). The study aims to find potential anti-infective catheter-coating agents to prevent CAUTIs.

Key Takeaways:

1. The study found synergistic, additive, and antagonistic interactions between biocides and QSIs at bacteriostatic, bactericidal, and biofilm eradication concentrations.

2. PHMB and silver in combination with cinnamaldehyde displayed synergistic antimicrobial activity against UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.

3. The test biocides and QSIs have various growth inhibitory and bactericidal modes of action that may account for the synergism observed at bacteriostatic and bactericidal concentrations.