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Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant Staphylococcus
1Fundacion Lusara, Mexico City 08810, Mexico.
Abstract:
Macrolides inhibit biofilm formation in several Gram-negative, intrinsically-resistant bacterial species. However, the effect of macrolides upon biofilm formation by susceptible Gram-positive bacteria has been much less explored as such concentrations also inhibit cell growth. To circumvent this problem, the effect of macrolides (erythromycin, clarithromycin and azithromycin) at 0.5-2 µg/mL, upon biofilm formation, was explored on macrolide-resistant Staphylococcus aureus isolates, using the crystal violet assay with 96-well plates. Early (4 h) biofilm formation by strains having constitutive target-modification resistance was consistently induced by all macrolides but not in azithromycin-treated cells in longer (8 and 12 h) incubation. In inducible-resistance isolates, early biofilm formation was enhanced by some macrolide treatments, compared to similar cell growth in the absence of antibiotics; but the typical decay of biofilms at longer incubation appeared prematurely in macrolide-treated cultures. Biofilm formation in an efflux-mediated resistant isolate was not affected by macrolides. These results indicate that macrolides induce the formation of biofilm by resistant S. aureus isolates, especially during the early stages. This suggests that the empirical use of macrolides against infections caused by resistant S. aureus strains could not only result in clinical failure but even in the enhancement of biofilms, making further treatment difficult.
Insights
Macrolides can unexpectedly enhance biofilm formation in resistant Staphylococcus aureus strains, potentially leading to treatment failure. This finding highlights risks associated with empirical macrolide use in S. aureus infections.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Macrolides are known to inhibit biofilm formation in Gram-negative bacteria.
- The impact of macrolides on biofilm formation in susceptible Gram-positive bacteria is less understood due to growth-inhibitory concentrations.
- Macrolide resistance mechanisms in Staphylococcus aureus include target modification and efflux pumps.
Purpose of the Study:
- To investigate the effect of sub-inhibitory concentrations of macrolides (erythromycin, clarithromycin, azithromycin) on biofilm formation in macrolide-resistant Staphylococcus aureus isolates.
- To explore how different resistance mechanisms influence the interaction between macrolides and S. aureus biofilm development.
Main Methods:
- Utilized the crystal violet assay in 96-well plates to quantify biofilm formation.
- Tested macrolide concentrations ranging from 0.5-2 µg/mL.
- Examined biofilm formation at early (4 h) and later (8 and 12 h) incubation times across various S. aureus isolates with different resistance profiles.
Main Results:
- Macrolides consistently induced early biofilm formation in S. aureus strains with constitutive target-modification resistance.
- Azithromycin did not induce biofilm formation in longer incubation periods (8 and 12 h) for these strains.
- Inducible resistance isolates showed enhanced early biofilm formation with macrolide treatment, but premature biofilm decay at later stages.
- Biofilm formation in efflux-mediated resistant isolates remained unaffected by macrolides.
Conclusions:
- Macrolides can induce biofilm formation in resistant Staphylococcus aureus isolates, particularly during early developmental stages.
- Empirical use of macrolides against resistant S. aureus may lead to clinical failure and increased biofilm formation, complicating treatment.
- Understanding macrolide-resistance interplay is crucial for effective therapeutic strategies against S. aureus infections.
