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Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus
Apostolos Liakopoulos1, Roberto M La Ragione2, Christoph Nagel3
1Department Microbial Biotechnology and Health, Institute of Biology Leiden, University of Leiden, Leiden, Netherlands.
Objectives:
The emergence of multidrug-resistance (MDR) in Streptococcus pneumoniae clones and non-vaccine serotypes necessitate the development of novel treatment strategies. This work aimed to determine the efficacy of the Mn complex [Mn(CO)3(tpa-κ3N)]Br against clinically important MDR strains of S. pneumoniae.
Methods:
Twenty MDR clinicalS. pneumoniae strains were included in this study. Minimum inhibitory concentrations (MICs) of [Mn(CO)3(tpa-κ3N)]Br were determined via broth microdilution alone and in combination with other antimicrobial agents using checkerboard assays and/or disc diffusion tests. In vitro efficacy was assessed by time-kill assays while in vivo efficacy was tested using the insect model Galleria mellonella.
Results:
[Mn(CO)3(tpa-κ3N)]Br showed moderate in vitro efficacy against S. pneumoniae coupled with bactericidal activity. Checkerboard and disc diffusion assays showed synergy between [Mn(CO)3(tpa-κ3N)]Br and tetracycline, and the combination of both agents caused rapid kill-kinetics and reduced the MIC below the susceptibility breakpoint of 1 mg/L even for tetracycline-resistant strains of S. pneumoniae. Similar results were observed for the erythromycin- and the co-trimoxazole-Mn complex combination. In the G. mellonella infection model, mortality and morbidity rates at 96 h were significantly lower in larvae treated with [Mn(CO)3(tpa-κ3N)]Br than phosphate buffered saline, while treatment with the tetracycline-Mn complex combination was superior to monotherapy, resulting in significantly lower mortality and morbidity rates (p < 0.049).
Conclusions:
We show that [Mn(CO)3(tpa-κ3N)]Br has in vitro and in vivo antibacterial activity against clinically relevant strains of S. pneumoniae and has the potential to be used in combination with currently available antibiotics to increase their effectiveness against MDR S. pneumoniae.
Insights
The manganese complex [Mn(CO)3(tpa-κ3N)]Br shows antibacterial activity against multidrug-resistant Streptococcus pneumoniae. Combining this complex with tetracycline enhances its effectiveness, offering a potential new strategy for treating resistant pneumococcal infections.
Area of Science:
- Inorganic Chemistry
- Microbiology
- Pharmacology
Background:
- Emergence of multidrug-resistant (MDR) Streptococcus pneumoniae necessitates novel therapeutic strategies.
- Non-vaccine serotypes of S. pneumoniae pose a growing public health challenge.
- Development of new antimicrobial agents is crucial to combat resistant bacterial strains.
Purpose of the Study:
- To evaluate the efficacy of the manganese complex [Mn(CO)3(tpa-κ3N)]Br against clinically significant MDR S. pneumoniae strains.
- To investigate the synergistic potential of [Mn(CO)3(tpa-κ3N)]Br in combination with existing antibiotics.
- To assess the in vitro and in vivo antibacterial activity of the Mn complex.
Main Methods:
- Minimum inhibitory concentrations (MICs) were determined using broth microdilution.
- Synergy was assessed via checkerboard and disc diffusion assays.
- In vitro time-kill assays and in vivo Galleria mellonella infection models were employed.
Main Results:
- The Mn complex demonstrated moderate in vitro efficacy and bactericidal activity against S. pneumoniae.
- Synergy was observed between [Mn(CO)3(tpa-κ3N)]Br and tetracycline, erythromycin, and co-trimoxazole.
- Combination therapy significantly reduced bacterial load and improved outcomes in a G. mellonella infection model.
Conclusions:
- [Mn(CO)3(tpa-κ3N)]Br exhibits promising in vitro and in vivo antibacterial activity.
- The Mn complex has potential for combination therapy to enhance antibiotic effectiveness against MDR S. pneumoniae.
- This study highlights a novel approach to combatting antibiotic resistance in S. pneumoniae.
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