Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of
            <i>Burkholderia mallei</i>

Ulrich, Ricky L.; DeShazer, David; Hines, Harry B.; Jeddeloh, Jeffrey A.

doi:10.1128/iai.72.11.6589-6596.2004

Cited by 69 publications

(74 citation statements)

References 38 publications

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“…In the past, Syrian hamsters had been the most effective model to study the pathogenicity of B. mallei when infected intraperitoneally [7,8,9,29]. However, purchasing and handling of Syrian hamsters is costlier than mice.…”

Section: Discussionmentioning

confidence: 99%

“…Burkholderia mallei, glanders, sucrose-resistant strain, recombination, ctpA, carboxy-terminal protease, attenuation, efficacy, laboratory animals, mice network [9], and a type VI secretion system [10] are important for the virulence of this bacterium. Molecular characterization of the in vivo survival process (or pathogenicity) of B. mallei is important because it would provide guidance for the development of measures for the prevention and control of glanders.…”

Section: Subject Termsmentioning

confidence: 99%

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A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia mallei and induces partial protection in CD1 mice

Bandara

DeShazer

Inzana

et al. 2008

Microbial Pathogenesis

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Section: Discussionmentioning

confidence: 99%

Section: Subject Termsmentioning

confidence: 99%

A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia mallei and induces partial protection in CD1 mice

Bandara

DeShazer

Inzana

et al. 2008

Microbial Pathogenesis

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“…This appears to be the case for the 120-kb R2-I2-containing DNA element. Other investigators have shown that both of the B. mallei quorum-sensing systems contribute to virulence (61). It is logical to assume that system 2 in B. pseudomallei is not critical for virulence.…”

Section: Vol 191 2009mentioning

confidence: 99%

“…pseudomallei-B. thailandensis group because quorum sensing has been implicated in the virulence of B. mallei and B. pseudomallei and because each member of this group has multiple quorumsensing systems (60)(61)(62). Quorum sensing involves production of and response to a self-produced extracellular signal that allows individuals to monitor the group population density (3,21,67).…”

Section: Burkholderia Thailandensis Burkholderia Pseudomallei Andmentioning

confidence: 99%

Quorum-Sensing Control of Antibiotic Synthesis in Burkholderia thailandensis

et al. 2009

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The genome of Burkholderia thailandensis codes for several LuxR-LuxI quorum-sensing systems. We used B. thailandensis quorum-sensing deletion mutants and recombinant Escherichia coli to determine the nature of the signals produced by one of the systems, BtaR2-BtaI2, and to show that this system controls genes required for the synthesis of an antibiotic. BtaI2 is an acyl-homoserine lactone (acyl-HSL) synthase that produces two hydroxylated acyl-HSLs, N-3-hydroxy-decanoyl-HSL (3OHC 10 -HSL) and N-3-hydroxyoctanoyl-HSL (3OHC 8 -HSL). The btaI2 gene is positively regulated by BtaR2 in response to either 3OHC 10 -HSL or 3OHC 8 -HSL. The btaR2-btaI2 genes are located within clusters of genes with annotations that suggest they are involved in the synthesis of polyketide or peptide antibiotics. Stationary-phase cultures of wild-type B. thailandensis, but not a btaR2 mutant or a strain deficient in acyl-HSL synthesis, produced an antibiotic effective against gram-positive bacteria. Two of the putative antibiotic synthesis gene clusters require BtaR2 and either 3OHC 10 -HSL or 3OHC 8 -HSL for activation. This represents another example where antibiotic synthesis is controlled by quorum sensing, and it has implications for the evolutionary divergence of B. thailandensis and its close relatives Burkholderia pseudomallei and Burkholderia mallei. Burkholderia thailandensis, Burkholderia pseudomallei, andBurkholderia mallei are closely related betaproteobacteria. These three species show extensive genome sequence identity (37, 72). B. mallei is an obligate mammalian pathogen that infects solipeds (horses, mules, and donkeys) and can also cause human infections (66, 69). B. pseudomallei is an emerging human pathogen found in soil and stagnant water, and it infects rice farmers in Southeast Asia and people of Northern Australia (8,70). Once thought to be a nonpathogenic saprophyte endemic to the water and soil environments of central and northeastern Thailand (4), B. thailandensis has recently been found in the central United States and Australia (25,34). Sufficiently high doses of B. thailandensis can cause mammalian infections (4,11,56).We have been interested in acyl-homoserine lactone (acyl-HSL) quorum sensing among the B. mallei-B. pseudomallei-B. thailandensis group because quorum sensing has been implicated in the virulence of B. mallei and B. pseudomallei and because each member of this group has multiple quorumsensing systems (60-62). Quorum sensing involves production of and response to a self-produced extracellular signal that allows individuals to monitor the group population density (3,21,67). Proteobacteria often use acyl-HSL signals for quorum sensing. The signals are produced by members of the LuxI family of acyl-HSL synthases. The proteins that respond to acyl-HSLs are members of the LuxR family of transcription factors (22). Dozens of species possess acyl-HSL quorum-sensing systems. The genes coding for LuxR and LuxI homologs are often adjacent on a chromosome and are considered cognate pairs. The nature of the...

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“…This interaction leads to conformational changes of the regulator and subsequent modifications of target gene transcription. The phenotypes regulated by QS are as diverse as bioluminescence (37), competence (49), biofilm formation (44), and virulence (50,75,78).We identified two LuxR-type regulators in the sequenced B. melitensis genome (16), the previously described VjbR regulator (BMEI1116) (14) and a second regulator, currently undergoing characterization, called BabR (BMEI1758). Despite several attempts, we were not able to identify an AHL synthetase in B. melitensis.…”

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confidence: 99%

Mutations of the Quorum Sensing-Dependent Regulator VjbR Lead to Drastic Surface Modifications inBrucella melitensis

et al. 2007

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Successful establishment of infection by bacterial pathogens requires fine-tuning of virulence-related genes. Quorum sensing (QS) is a global regulation process based on the synthesis of, detection of, and response to small diffusible molecules, called N-acyl-homoserine lactones (AHL), in gram-negative bacteria. In numerous species, QS has been shown to regulate genes involved in the establishment of pathogenic interactions with the host. Brucella melitensis produces N-dodecanoyl homoserine lactones (C 12 -HSL), which down regulate the expression of flagellar genes and of the virB operon (encoding a type IV secretion system), both of which encode surface virulence factors. A QS-related regulator, called VjbR, was identified as a transcriptional activator of these genes. We hypothesized that VjbR mediates the C 12 -HSL effects described above. vjbR alleles mutated in the region coding for the AHL binding domain were constructed to test this hypothesis. These alleles expressed in trans in a ⌬vjbR background behave as constitutive regulators both in vitro and in a cellular model of infection. Interestingly, the resulting B. melitensis strains, unable to respond to AHLs, aggregate spontaneously in liquid culture. Preliminary characterization of these strains showed altered expression of some outer membrane proteins and overproduction of a matrix-forming exopolysaccharide, suggesting for the first time that B. melitensis could form biofilms. Together, these results indicate that QS through VjbR is a major regulatory system of important cell surface structures of Brucella and as such plays a key role in host-pathogen interactions.Brucella spp. are gram-negative intracellular pathogens belonging to the ␣-2 proteobacteria group, like Agrobacterium, Rhizobium, and Rickettsia, which also live in close association with a eukaryotic host (46). Bacteria of the genus Brucella are the etiologic agents of brucellosis, a worldwide zoonosis affecting a broad range of mammals and triggering important economic losses (63). Three Brucella species, B. melitensis, B. abortus, and B. suis, are able to infect humans, causing a chronic, debilitating disease with severe, sometimes fatal outcomes.Brucellae are remarkably well adapted to the intracellular lifestyle, being able to invade and to survive within macrophages and nonprofessional phagocytes (17,51). This is one of the bases for the still poorly understood chronicity of brucellosis (26). This aptitude relies on the perturbation of vesicular trafficking and the creation of a unique intracellular replication niche derived from the endoplasmic reticulum (7,8).Brucella is confronted with very diverse environments and host defenses both in the extracellular milieu and inside host cells. It is thus expected that this pathogen has to sense external and internal signals to achieve successful adaptation throughout its infectious cycle. Among such systems, quorum sensing (QS), stringent response, and signal transduction through two-component regulators have been particularly well studied (fo...

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Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

Cited by 69 publications

References 38 publications

A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia mallei and induces partial protection in CD1 mice

A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia mallei and induces partial protection in CD1 mice

Quorum-Sensing Control of Antibiotic Synthesis in Burkholderia thailandensis

Mutations of the Quorum Sensing-Dependent Regulator VjbR Lead to Drastic Surface Modifications inBrucella melitensis

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