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Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants.

ABSTRACT: Mycoplasma pneumoniae is one of the leading causes of community-acquired pneumonia in children and adolescents. Because of the wide application of macrolides in clinical treatment, macrolide-resistant M. pneumoniae strains have become increasingly common worldwide. However, the molecular mechanisms underlying drug resistance in M. pneumoniae are poorly understood. In the present work, we analyzed the whole proteomes of macrolide-sensitive and macrolide-resistant strains of M. pneumoniae using a tandem mass tag-labeling quantitative proteomic technique, Data are available via ProteomeXchange with identifier PXD022220. In total, 165 differentially expressed proteins were identified, of which 80 were upregulated and 85 were downregulated in the drug-resistant strain compared with the sensitive strain. Functional analysis revealed that these proteins were predominantly involved in protein and peptide biosynthesis processes, the ribosome, and transmembrane transporter activity, which implicates them in the mechanism(s) of resistance of M. pneumoniae to macrolides. Our results provide new insights into drug resistance in M. pneumoniae and identify potential targets for further studies on resistance mechanisms in this bacterium.

SUBMITTER: Li S

PROVIDER: S-EPMC7881084 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants.

Li Shaoli S Xue Guanhua G Zhao Hanqing H Feng Yanling Y Yan Chao C Cui Jinghua J Xie Xianghui X Yuan Jing J

AMB Express 20210212 1

Mycoplasma pneumoniae is one of the leading causes of community-acquired pneumonia in children and adolescents. Because of the wide application of macrolides in clinical treatment, macrolide-resistant M. pneumoniae strains have become increasingly common worldwide. However, the molecular mechanisms underlying drug resistance in M. pneumoniae are poorly understood. In the present work, we analyzed the whole proteomes of macrolide-sensitive and macrolide-resistant strains of M. pneumoniae using a ...[more]

PMID: 33580372

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Project description:Abstract Background Mycoplasma pneumoniae(Mp) is one of the most common causes of LRTI in school aged children, with estimates of up to 20% of cases of community-acquired pneumonia (CAP). Macrolides are the drug of choice for treating Mp infections, but in the last 2 decades there has been emergence of resistance worldwide. Reported rates in USA vary from 3.5 up to 10.8%, but rates in Ohio are unknown. Currently there is no well-established, standardized method for detecting macrolide resistance and antibiotic treatment is empiric because of these limitations. Our goal was to determine the frequency of macrolide resistance in children with Mp respiratory infections in central Ohio. Methods A convenience sample of Mp positive PCR identified by our laboratory-developed assay, obtained from both inpatient and outpatient settings, were selected. These were then cultured using Remel’s SP4 glucose broth and then incubated at 35°C until isolates grew, or for a maximum of 4 weeks. All samples that yield positive cultures were then sequenced for the domain V of the 23S rRNA (nucleotide 1937–2154, accession no. X68422) using Sanger methods and sequences were compared with corresponding region of wildtype reference strain (ATCC 15322). Results For the period of October 2015-March 2017, culture was attempted in 433 PCR-positive samples, and 347 (80%) yield an isolate. Sequencing was performed in those 347 samples and was successful in 334 (96%). A macrolide resistance mutation was detected in 10 samples (3%). From the 10 mutations detected, 7 (70%) were the A2063G mutation, and 3 (30%) were A2064G. We also detected a deletion in A2065 of unknown significance in 3 samples (0.9%). Conclusion In this pediatric population, culture was successful in 80% of PCR positive samples, thus providing isolates for sequencing to be able to assess our local resistance. Our overall Mp resistance was 3%, suggesting that empiric treatment with macrolides is still appropriate in Central Ohio. Additional studies are needed to correlate the presence of these resistance mutations with phenotypic susceptibility testing and clinical outcomes. Disclosures O. Ramilo, Abbvie: Board Member, Consulting fee; Regeneron: Board Member, Consulting fee; Janssen: Board Member and Investigator, Consulting fee and Research grant; NIH: Grant Investigator, Research grant; A. Leber, BioFIre Dia gnostics: Research Contractor and Scientific Advisor, Research support, Speaker honorarium and Travel expenses

Dataset Information

Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants.

Publications

Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants.

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