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Published on: December 16, 2021
Global Proteome Profiling Reveals Drug-Resistant Traits in Elizabethkingia meningoseptica: An Opportunistic
Archana Agrawal1, Raju Ravikumar1, Chakrakodi N Varun1
11 Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Abstract:
Elizabethkingia meningoseptica is Gram-negative, rod-shaped opportunistic bacterial pathogen increasingly reported in hospital-acquired outbreaks. This bacterium is well known to thrive in the hospital environment. One of the leading causes of meningitis in pediatric and immune-compromised patients, E. meningoseptica has been noted as a "pathogen of interest" in the context of nosocomial diseases associated with device-related infections in particular. This pathogen's multidrug-resistant phenotype and attendant lack of adequate molecular mechanistic data limit the current approaches for its effective management in hospitals and public health settings. This study provides the global proteome of E. meningoseptica. The reference strain E. meningoseptica ATCC 13253 was used for proteomic analysis using high-resolution Fourier transform mass spectrometry. The study provided translational evidence for 2506 proteins of E. meningoseptica. We identified multiple metallo-β-lactamases, transcriptional regulators, and efflux transporter proteins associated with multidrug resistance. A protein Car D, which is an enzyme of the carbapenem synthesis pathway, was also discovered in E. meningoseptica. Further, the proteomics data were harnessed for refining the genome annotation. We discovered 39 novel protein-coding genes and corrected four existing translations using proteogenomic workflow. Novel translations reported in this study enhance the molecular data on this organism, thus improving current databases. We believe that the in-depth proteomic data presented in this study offer a platform for accelerated research on this pathogen. The identification of multiple proteins, particularly those involved in drug resistance, offers new future opportunities to design novel and specific antibiotics against infections caused by E. meningoseptica.
Insights
This study presents the first global proteome of Elizabethkingia meningoseptica, identifying 2506 proteins. This research enhances understanding of this multidrug-resistant pathogen and aids in developing new treatments for hospital-acquired infections.
Area of Science:
- Microbiology
- Proteomics
- Genomics
Background:
- Elizabethkingia meningoseptica is an opportunistic Gram-negative pathogen causing hospital-acquired infections, particularly meningitis in vulnerable populations.
- Its multidrug resistance and limited molecular data hinder effective clinical management and public health strategies.
- E. meningoseptica is recognized as a significant nosocomial pathogen, especially in device-related infections.
Purpose of the Study:
- To provide the first comprehensive global proteome of Elizabethkingia meningoseptica.
- To identify proteins associated with multidrug resistance and other virulence factors.
- To refine genome annotation and discover novel protein-coding genes using a proteogenomic approach.
Main Methods:
- Proteomic analysis of the reference strain E. meningoseptica ATCC 13253 using high-resolution Fourier transform mass spectrometry.
- Application of a proteogenomic workflow to harness proteomics data for genome annotation refinement.
- Identification and characterization of translated proteins, including those involved in drug resistance.
Main Results:
- Translational evidence for 2506 proteins in E. meningoseptica was established.
- Multiple proteins linked to multidrug resistance, including metallo-β-lactamases, transcriptional regulators, and efflux transporters, were identified.
- A carbapenem synthesis pathway enzyme, CarD, was discovered, along with 39 novel protein-coding genes, and four existing translations were corrected.
Conclusions:
- The comprehensive proteomic data enhances molecular understanding of E. meningoseptica.
- The identification of drug resistance proteins offers targets for developing novel antibiotics.
- This study provides a foundation for accelerated research into E. meningoseptica infections and improved therapeutic strategies.
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