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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Comparative genomic analysis of Brucella melitensis vaccine strain M5 provides insights into virulence attenuation
Hai Jiang1, Pengcheng Du, Wen Zhang
1State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Beijing, China.
Abstract:
The Brucella melitensis vaccine strain M5 is widely used to prevent and control brucellosis in animals. In this study, we determined the whole-genome sequence of M5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 M and other reference strains. This analysis revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI showed consistent variation, with a large deletion between the M5 and the 16 M genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing different Brucella strains. Other RD and RI regions exhibited multiple single nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb rearrangement was determined to be consistent with previous studies. Comparative genomic analysis indicated that genomic island inversion in Brucella was widely present. With the genetic pattern common among all strains analyzed, these 2 RDs, 1 RI, and one inversion region are potential sites for detection of genomic differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB, dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the mechanism of virulence attenuation. Collectively, this study reveals that comparative analysis between wild-type and vaccine strains can provide resources for the study of virulence and microevolution of Brucella.
Insights
Comparative genomics of Brucella melitensis vaccine strain M5 reveals genomic differences from virulent strains. Key deletion and insertion regions, like RD4 and RD5, offer potential for typing Brucella strains and understanding virulence attenuation.
Area of Science:
- Genomics
- Microbiology
- Veterinary Science
Background:
- Brucella melitensis vaccine strain M5 is crucial for animal brucellosis control.
- Understanding genomic variations between vaccine and virulent strains is vital for vaccine efficacy and strain differentiation.
Purpose of the Study:
- To determine the whole-genome sequence of Brucella melitensis vaccine strain M5.
- To perform a comparative genomic analysis against virulent strain 16 M and other reference strains.
- To identify genomic regions useful for Brucella strain typing and understanding virulence attenuation.
Main Methods:
- Whole-genome sequencing of Brucella melitensis M5.
- Comparative genomic analysis with virulent Brucella strains.
- Identification and characterization of deletions, insertions, single nucleotide polymorphisms (SNPs), and genomic rearrangements.
Main Results:
- Identified 11 regions of deletion (RDs) and 2 regions of insertion (RIs) in the M5 genome.
- RD4 and RD5 exhibited significant diversity in length and copy number, suitable for strain typing.
- Detected SNPs in virulence-related genes (e.g., motB, aroC) and a 56 kb genomic rearrangement.
- Comparative analysis revealed widespread genomic island inversion in Brucella.
Conclusions:
- Comparative genomics between vaccine and wild-type Brucella strains provides insights into virulence and microevolution.
- Specific RDs, RIs, and inversion regions are valuable for detecting genomic differences and typing Brucella strains.
- SNPs in virulence genes may elucidate mechanisms of virulence attenuation in vaccine strains.
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