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Microb Pathog. 2017 Aug;109:313-318. doi: 10.1016/j.micpath.2017.04.040. Epub 2017 May 4.

Effects of lipid A acyltransferases on the pathogenesis of F. novicida.

Author information

1
Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.
2
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.
3
National Engineering Laboratory for Cereal Fermentation Technology of Jiangnan University, 1800 Lihu Road, Wuxi 214122, China. Electronic address: zhangl@jiangnan.edu.cn.
4
Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China. Electronic address: yanyanli1123@hotmail.com.

Abstract

Francisella novicida is a gram-negative pathogen commonly used to study infections by the potential bioterrorism agent, Francisella tularensis. The Francisella lipid A structure has been well characterized and showed to affect the pathogenesis of F. novicida. Previous work characterized two lipid A acyltransferases, LpxD1 and LpxD2, and constructed the lpxD1-null and lpxD2-null mutants. Mutational analysis showed the lpxD1-null mutant was attenuated in mice and subsequently exhibited protection against a lethal WT challenge. However, details as how the virulence has been changed have remained elusive. This study aims to analyze effects of lipid A acyltransferases on the pathogenesis of F. novicida. MS and MSn were conducted to confirm the lipid A structures of lpxD1-null and lpxD2-null mutants. The stress tolerance, Toll-like receptor 4 (TLR4) stimulation level, intracellular survival and replication ability and cytotoxicity of lpxD1-null and lpxD2-null mutants were analyzed. The results suggested the lpxD1-null mutant with shorter acyl chains in lipid A is more sensitive to various environmental stresses than F. novicida and lpxD2-null mutant. In addition, the lpxD1-null mutant fails to survive and replicate in cells and shows lower cytotoxicity to infected cells. This study provides insights into the pathogenesis of F. novicida.

KEYWORDS:

Acyltransferases; Francisella novicida; Lipid A; lpxD-null mutants

PMID:
28478203
DOI:
10.1016/j.micpath.2017.04.040
[Indexed for MEDLINE]

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