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Galacto-Oligosaccharides as an Anti-Infective and Anti-Microbial Agent for Macrolide-Resistant and -Sensitive
Hongzhen Zhu1, Yang Cai2,3, Lisa J M Slimmen1
1Laboratory of Pediatrics, Department of Pediatrics, Erasmus MC, University Medical Centre Rotterdam, Sophia Children's Hospital, 3015 GD Rotterdam, The Netherlands.
Abstract:
The worldwide increase in the incidence of antibiotic resistance of the atypical bacterium Mycoplasma pneumoniae (MP) challenges the treatment of MP infections, especially in children. Therefore, alternative strategies for the treatment of MP infections are warranted. Galacto- and fructo-oligosaccharides (GOS and FOS) are a specific group of complex carbohydrates that were recently shown to possess direct anti-pathogenic properties. In this study, we assessed whether GOS and FOS exert anti-microbial and anti-infective effects against MP and, especially, macrolide-resistant MP (MRMP) in vitro. The MIC values of GOS for MP and MRMP were 4%. In contrast, the MIC values of FOS for both MP and MRMP were 16%. A time-kill kinetic assay showed that FOS possess bacteriostatic properties, while for GOS, a bactericidal effect against MP and MRMP was observed after 24 h at a concentration of 4x MIC. In co-cultures with human alveolar A549 epithelial cells, GOS killed adherent MP and MRMP and also concentration-dependently inhibited their adherence to A549 cells. Further, GOS suppressed (MR)MP-induced IL-6 and IL-8 in A549 cells. None of the aforementioned parameters were affected when FOS were added to these co-cultures. In conclusion, the anti-infective and anti-microbial properties of GOS could provide an alternative treatment against MRMP and MP infections.
Insights
Galacto-oligosaccharides (GOS) show promise as an alternative treatment for Mycoplasma pneumoniae infections. GOS demonstrated bactericidal effects and inhibited bacterial adherence and inflammation in vitro, unlike fructo-oligosaccharides (FOS).
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising antibiotic resistance in Mycoplasma pneumoniae (MP) necessitates novel therapeutic strategies, particularly for pediatric infections.
- Oligosaccharides, including galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS), have demonstrated direct anti-pathogenic activities.
Purpose of the Study:
- To evaluate the in vitro antimicrobial and anti-infective effects of GOS and FOS against both typical and macrolide-resistant Mycoplasma pneumoniae (MRMP).
Main Methods:
- Minimum Inhibitory Concentration (MIC) determination for GOS and FOS against MP and MRMP.
- Time-kill kinetic assays to assess bacteriostatic and bactericidal properties.
- In vitro co-culture models with A549 human alveolar epithelial cells to evaluate effects on bacterial adherence, viability, and host inflammatory responses (IL-6, IL-8).
Main Results:
- GOS exhibited lower MIC values (4%) compared to FOS (16%) against both MP and MRMP.
- GOS demonstrated bactericidal activity after 24 hours at 4x MIC, while FOS showed bacteriostatic properties.
- GOS effectively killed adherent MP/MRMP, inhibited bacterial adherence to A549 cells, and suppressed MP-induced IL-6 and IL-8 production; FOS had no significant effect on these parameters.
Conclusions:
- Galacto-oligosaccharides (GOS) possess significant anti-infective and antimicrobial properties against Mycoplasma pneumoniae, including macrolide-resistant strains.
- The findings suggest GOS could serve as a viable alternative therapeutic agent for treating MP infections, offering a new approach against antibiotic-resistant pathogens.
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