Characterization of Brucella abortus mutant strain \u039422915, a potential vaccine candidate

Yanqing Bao,Shengqing Yu,Peng Li,Jiameng Liu,Mingxing Tian,Chan Ding

doi:10.1186/s13567-017-0422-9

Yanqing Bao, Shengqing Yu + Show 4 more

Open Access

https://doi.org/10.1186/s13567-017-0422-9

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Abstract

Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 105 colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.

Highlights

Brucellosis is a zoonotic disease epidemic in Asia, South and Central America, and sub-Saharan Africa [1]
We demonstrated that the decreased intracellular survival of strain ∆22915 was associated with the altered capacity to exclude lysosomes, an important step before Brucella reaches a replicative niche in endoplasmic reticulum [34]
membrane-bound lytic transglycosylase B (MltB) is a member of the lytic transglycosylase (LT) family that is involved in recycling bacterial cell walls to produce 1,6-anhydromuropeptides for bacterial growth [35]

Summary

Introduction

Brucellosis is a zoonotic disease epidemic in Asia, South and Central America, and sub-Saharan Africa [1] It is caused by the genus Brucella, which infects millions of livestock and more than half a million people annually [2, 3]. Vaccination of healthy animals is an effective strategy for protecting livestock from Brucella infection in developing countries and protecting wildlife in developed countries [4]. Vaccine strains such as S19, RB51 and Rev. have been extensively applied over the past decades with promising effects. Residue pathogenicity to humans and pregnant animals, and potential virulence reversion risks require the development of safer and better vaccines [5, 6]

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