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Published on: February 23, 2014
Proteomic and Phenotypic Studies of Mycoplasma pneumoniae Revealed Macrolide-Resistant Mutation (A2063G) Associated
Zhikun Zhang1,2, Haiwei Dou1, Qing Yuan1
1Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Abstract:
Mycoplasma pneumoniae (MP) is an important respiratory pathogen, the prevalence of macrolide-resistant MP (mainly containing A2063G mutation in 23S rRNA) increased in recent years. Epidemiological studies suggest a higher prevalence of type I resistant (IR) strains than corresponding sensitive (IS/IIS) strains, but not type II resistant (IIR) strains. Here, we aimed to analyze the factors underlying the altered prevalence of IR strains. First, proteomic analyses exhibit the protein compositions were type specific, while more differential proteins were detected between IS and IR (227) than IIS and IIR strains (81). mRNA level detection suggested posttranscriptional regulation of these differential proteins. Differential protein-related phenotypic changes were also detected: (i) P1 abundance was different between genotypes (I < II, IR < IS), the adhesion of MPs showed accordance to P1 abundance within IS and IIS strains; (ii) type I, especially IR, strains had a higher proliferation rate, which is potentially associated with differential proteins participating in glycolysis and one carbon pool metabolisms; (iii) A549 cells infected with IR strains had lower activity of caspase-3 and higher levels IL-8, but the differences were not significant between groups (P > 0.05). Correlations of P1 abundance to caspase-3 activity and proliferation rate to the level of IL-8 were obtained. These results suggest changes in protein composition influenced the pathogenicity of MP, especially in IR strains, which may impact the prevalence of MP strains of different genotypes. IMPORTANCE The prevalence of macrolide-resistant MPs increased the difficulty in treatment of MP infections and posed potential threats to children's health. Epidemiological studies showed a high prevalence of IR-resistant strains (mainly A2063G in 23S rRNA) in these years. However, the trigger mechanisms for this phenomenon are not clear. In this paper, proteomic and phenotypic studies suggest that IR strains have reduced levels of multiple adhesion proteins and increased proliferation rate, which may lead to higher transmission rate of IR strains in the population. This suggests that we should pay attention to the prevalence of IR strains.
Insights
Macrolide-resistant Mycoplasma pneumoniae (MP) strains, particularly type I resistant (IR) strains, show altered protein profiles and increased proliferation rates. These changes in protein composition may drive the higher prevalence of IR strains, impacting MP infection treatment and children's health.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Macrolide-resistant Mycoplasma pneumoniae (MP) strains, characterized by the A2063G mutation, are increasing.
- Type I resistant (IR) MP strains are more prevalent than sensitive strains, but the reasons are unclear.
- Understanding the factors influencing IR strain prevalence is crucial for managing MP infections, especially in children.
Purpose of the Study:
- To investigate the underlying factors contributing to the altered prevalence of type I resistant (IR) Mycoplasma pneumoniae strains.
- To analyze proteomic and phenotypic differences between macrolide-resistant and sensitive MP strains.
- To correlate protein composition changes with MP pathogenicity and transmission potential.
Main Methods:
- Proteomic analysis to compare protein compositions between different MP genotypes (IS, IIS, IR, IIR).
- mRNA level detection to assess posttranscriptional regulation of differential proteins.
- Phenotypic assays to evaluate P1 protein abundance, MP adhesion, proliferation rates, and host cell responses (caspase-3 activity, IL-8 levels).
Main Results:
- Proteomic analysis revealed significant differences in protein composition, with more differential proteins between IS and IR strains (227) than between IIS and IIR strains (81).
- Type I resistant (IR) strains exhibited reduced P1 protein abundance and increased proliferation rates, potentially linked to altered glycolysis and one-carbon metabolism.
- Infection with IR strains showed a trend towards lower caspase-3 activity and higher IL-8 levels in A549 cells, though not statistically significant.
Conclusions:
- Altered protein composition, particularly reduced P1 abundance and increased proliferation in IR strains, significantly influences MP pathogenicity.
- These molecular and phenotypic changes in IR strains may contribute to their higher transmission rates and increased prevalence in the population.
- The findings highlight the need to monitor the prevalence of IR MP strains due to their potential impact on treatment efficacy and public health.
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