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The Effect of Erythromycin in Macrolide-resistant Bordetella pertussis: Inhibitory Effect on Growth, Toxin
Kaichong Jiang1, Yang Luan2, Wei Wang3
1National Regional Children's Medical Center (Northwest), Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital, Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China.
Introduction:
The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear.
Objective:
The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin.
Methods:
This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR.
Results:
The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin.
Conclusion:
The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.
Insights
Sub-inhibitory erythromycin may reduce the virulence of macrolide-resistant Bordetella pertussis (MRBp). This finding supports revising macrolide therapy for pertussis and developing new antibiotics against MRBp infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Macrolide-resistant Bordetella pertussis (MRBp) is prevalent, particularly in China.
- Macrolides are often the first-line treatment for MRBp infections despite unclear mechanisms.
- Current macrolide therapy for pertussis requires revision.
Purpose of the Study:
- To investigate the impact of sub-minimum inhibitory concentrations (sub-MIC) of erythromycin on MRBp virulence.
- To understand the mechanism of macrolide action on macrolide-resistant Bordetella pertussis.
Main Methods:
- Evaluated a representative MRBp isolate (BP19147) exposed to varying sub-MIC erythromycin concentrations.
- Assessed bacterial growth, biofilm formation, and autoaggregation.
- Utilized RT-qPCR for gene expression analysis and label-free DIA proteomics.
Main Results:
- Sub-MIC erythromycin inhibited MRBp growth ability and virulence factors in a concentration-dependent manner.
- Key virulence factors like dermonecrotic toxin and invasive adenylate cyclase were significantly affected (p <0.05).
- Erythromycin impacted the BvgAS system, biofilm formation, and adaptive systems.
Conclusions:
- Sub-MIC erythromycin potentially reduces MRBp virulence.
- Provides a theoretical basis for rational erythromycin use in MRBp infections.
- Aids in the development of novel antibiotics targeting MRBp.
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