title: Impact of Hfq on global gene expression and intracellular survival in Brucella melitensis.
abstract: Brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. The ability of brucellae to survive and multiply in the hostile environment of host macrophages is essential to its virulence. The RNA-binding protein Hfq is a global regulator that is involved in stress resistance and pathogenicity. Here we demonstrate that Hfq is essential for stress adaptation and intracellular survival in B. melitensis. A B. melitensis hfq deletion mutant exhibits reduced survival under environmental stresses and is attenuated in cultured macrophages and mice. Microarray-based transcriptome analyses revealed that 359 genes involved in numerous cellular processes were dysregulated in the hfq mutant. From these same samples the proteins were also prepared for proteomic analysis to directly identify Hfq-regulated proteins. Fifty-five proteins with significantly affected expression were identified in the hfq mutant. Our results demonstrate that Hfq regulates many genes and/or proteins involved in metabolism, virulence, and stress responses, including those potentially involved in the adaptation of Brucella to the oxidative, acid, heat stress, and antibacterial peptides encountered within the host. The dysregulation of such genes and/or proteins could contribute to the attenuated hfq mutant phenotype. These findings highlight the involvement of Hfq as a key regulator of Brucella gene expression and facilitate our understanding of the role of Hfq in environmental stress adaptation and intracellular survival of B. melitensis.
authors: Department of Infectious Disease Control, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China ; College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, China.
authors: Mingquan
authors: M
authors: Cui
authors: Tongkun
authors: T
authors: Wang
authors: Jie
authors: J
authors: Xu
authors: Yuehua
authors: Y
authors: Ke
authors: Xinying
authors: X
authors: Du
authors: Xitong
authors: X
authors: Yuan
authors: Zhoujia
authors: Z
authors: Wang
authors: Chunli
authors: C
authors: Gong
authors: Yubin
authors: Y
authors: Zhuang
authors: Shuangshuang
authors: S
authors: Lei
authors: Xiao
authors: X
authors: Su
authors: Xuesong
authors: X
authors: Wang
authors: Liuyu
authors: L
authors: Huang
authors: Zhijun
authors: Z
authors: Zhong
authors: Guangneng
authors: G
authors: Peng
authors: Jing
authors: J
authors: Yuan
authors: Zeliang
authors: Z
authors: Chen
authors: Yufei
authors: Y
authors: Wang
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017347:Brucella melitensis / Q000502:physiology*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology*; D002460:Cell Line; D005260:Female; D005407:Flagella / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D035001:Host Factor 1 Protein
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