Decreased<i>in vivo</i>virulence and altered gene expression by a<i>Brucella melitensis</i>light-sensing histidine kinase mutant

Gourley, Christopher R.; Petersen, Erik; Harms, Jerome S.; Splitter, Gary A.

doi:10.1111/2049-632x.12209

Cited by 16 publications

(7 citation statements)

References 51 publications

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“…However, light does not seem to play a role during oxidative stress survival. Similar patterns have been identified for Brucella melitensis , where BM‐LOV‐HK promotes infection, but also modulates the expression of genes for quorum sensing, GSR, flagellar motion and type IV secretion .…”

Section: Lov‐regulated Patterns and Lifestyles In Bacteriasupporting

confidence: 70%

The Evolution and Functional Role of Flavin‐based Prokaryotic Photoreceptors

Losi

Mandalari

Gärtner

2015

Photochem & Photobiology

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Flavin-based photoreceptor proteins of the LOV (light, oxygen and voltage) superfamily are ubiquitous and appear to be essential blue-light sensing systems not only in plants, algae and fungi, but also in prokaryotes, where they are represented in more than 10% of known species. Despite their broad occurrence, only in few cases LOV proteins have been correlated with important phenomena such as bacterial infectivity, selective growth patterns or/and stress responses; nevertheless these few known roles are helping us understand the multiple ways by which prokaryotes can exploit these soluble blue-light photoreceptors. Given the large number of sequences now deposited in databases, it becomes meaningful to define a signature for bona fide LOV domains, a procedure that facilitates identification of proteins with new properties and phylogenetic analysis. The latter clearly evidences that a class of LOV proteins from alpha-proteobacteria is the closest prokaryotic relative of eukaryotic LOV domains, whereas cyanobacterial sequences cluster with the archaeal and the other bacterial LOV domains. Distance trees built for LOV domains suggest complex evolutionary patterns, possibly involving multiple horizontal gene transfer events. Based on available data, the in vivo relevance and evolution of prokaryotic LOV is discussed.

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Section: Lov‐regulated Patterns and Lifestyles In Bacteriasupporting

confidence: 70%

The Evolution and Functional Role of Flavin‐based Prokaryotic Photoreceptors

Losi

Mandalari

Gärtner

2015

Photochem & Photobiology

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“…At the time of writing, Gourley et al ., 2014, demonstrated by a microarray analysis that genes related to the GSR system and virB operon are differently regulated in a lovhk mutant strain of B . melitensis as compared with wt [ 61 ]. Here we further demonstrated a biochemical and physiological regulation of these genes in B .…”

Section: Discussionmentioning

confidence: 99%

LOV Histidine Kinase Modulates the General Stress Response System and Affects the virB Operon Expression in Brucella abortus

et al. 2015

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Brucella is the causative agent of the zoonotic disease brucellosis, and its success as an intracellular pathogen relies on its ability to adapt to the harsh environmental conditions that it encounters inside the host. The Brucella genome encodes a sensor histidine kinase containing a LOV domain upstream from the kinase, LOVHK, which plays an important role in light-regulated Brucella virulence. In this report we study the intracellular signaling pathway initiated by the light sensor LOVHK using an integrated biochemical and genetic approach. From results of bacterial two-hybrid assays and phosphotransfer experiments we demonstrate that LOVHK functionally interacts with two response regulators: PhyR and LovR, constituting a functional two-component signal-transduction system. LOVHK contributes to the activation of the General Stress Response (GSR) system in Brucella via PhyR, while LovR is proposed to be a phosphate-sink for LOVHK, decreasing its phosphorylation state. We also show that in the absence of LOVHK the expression of the virB operon is down-regulated. In conclusion, our results suggest that LOVHK positively regulates the GSR system in vivo, and has an effect on the expression of the virB operon. The proposed regulatory network suggests a similar role for LOVHK in other microorganisms.

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“…B. abortus also encodes a flavin-binding HWE kinase, LovhK, which has been previously shown to function as a blue-light regulated determinant of intracellular replication (Swartz et al, 2007). In Brucella melitensis, the orthologue of LovhK known as BM-LOV-HK has recently been shown to directly or indirectly modulate expression of genes involved in GSR, Type IV secretion, and quorum sensing (Gourley et al, 2014). However, the direct molecular signalling partner(s) of Brucella LovhK remain undefined.…”

Section: Lovhk Is a Phyr Kinase That Regulates Oxidative And Acid Strmentioning

confidence: 99%

The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway

Kim

Willett

Jain-Gupta

et al. 2014

Molecular Microbiology

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Summary In the intracellular pathogen Brucella abortus, the general stress response (GSR) signaling system determines survival under acute stress conditions in vitro, and is required for long-term residence in a mammalian host. To date, the identity of the Brucella sensor kinase(s) that function to perceive stress and directly activate GSR signaling have remained undefined. We demonstrate that the flavin-binding sensor histidine kinase, LovhK (bab2_0652), functions as a primary B. abortus GSR sensor. LovhK efficiently and specifically phosphorylates the central GSR regulator, PhyR, and activates transcription of a set of genes that closely overlaps the known B. abortus GSR regulon. Deletion of lovhK severely compromises cell survival under defined oxidative and acid stress conditions. We further show that lovhK is required for cell survival during the early phase of mammalian cell infection and for establishment of long-term residence in a mouse infection model. Finally, we present evidence that particular regions of primary structure within the two N-terminal PAS domains of LovhK have distinct sensory roles under specific environmental conditions. This study elucidates new molecular components of a conserved signaling pathway that regulates B. abortus stress physiology and infection biology.

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Decreasedin vivovirulence and altered gene expression by aBrucella melitensislight-sensing histidine kinase mutant

Cited by 16 publications

References 51 publications

The Evolution and Functional Role of Flavin‐based Prokaryotic Photoreceptors

The Evolution and Functional Role of Flavin‐based Prokaryotic Photoreceptors

LOV Histidine Kinase Modulates the General Stress Response System and Affects the virB Operon Expression in Brucella abortus

The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway

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