Smooth to Rough Dissociation in Brucella: The Missing Link to Virulence

Mancilla, Marcos

doi:10.3389/fcimb.2015.00098

Cited by 26 publications

(31 citation statements)

References 64 publications

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“…We discovered 14 such synthetic lethal genes in B. abortus ( Figure 6B and C) that have all been previously reported to play a role in O-polysaccharide synthesis (10,(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68); mutations in this gene set result in a rough phenotype in Brucella melitensis (58). It is well established that B. ovis is a rough strain that lacks LPS Opolysaccharide (28,58,69,70). Indeed, many of the O-polysaccharide genes that are synthetically lethal with eipA in B. abortus are frame-shifted, carry nonsense mutations, or are absent from the genome of B. ovis ( Figure 6C) (28,71).…”

Section: Eipa Is Essential In Brucella Ovis and Is Synthetically Lethmentioning

confidence: 80%

Periplasmic protein EipA determines envelope stress resistance and virulence inBrucella abortus

Herrou¹,

Willett²,

Fiebig³

et al. 2018

Preprint

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Molecular components of the Brucella abortus cell envelope, including lipopolysaccharide, play a major role in its ability to infect, colonize and survive inside mammalian host cells. We have defined a role for a conserved gene of unknown function in B. abortus envelope stress resistance and infection. Expression of this gene, which we name eipA, is directly activated by the essential cell cycle regulator, CtrA. eipA encodes a soluble periplasmic protein that adopts an unusual eight-stranded β -barrel fold. Deletion of eipA attenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to cell envelope stressors in vitro. Transposon disruption of genes required for LPS O-polysaccharide biosynthesis is synthetically lethal with eipA deletion. This genetic connection between O-polysaccharide and eipA is corroborated by our discovery that eipA is essential in Brucella ovis, a rough species that harbors mutations in several genes required for O-polysaccharide production. Conditional depletion of eipA expression in B. ovis results in a cell chaining phenotype, providing evidence that eipA directly or indirectly influences cell division in Brucella. Our data provide evidence that EipA is a molecular determinant of Brucella virulence that functions to maintain cell envelope integrity and influences cell division.

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Section: Eipa Is Essential In Brucella Ovis and Is Synthetically Lethmentioning

confidence: 80%

Periplasmic protein EipA determines envelope stress resistance and virulence inBrucella abortus

Herrou¹,

Willett²,

Fiebig³

et al. 2018

Preprint

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show abstract

“…B and C) that have been previously reported to play a role in O‐polysaccharide synthesis (Cloeckaert et al ., ; Ugalde et al ., ; Guzman‐Verri et al ., ; Monreal et al ., ; Manterola et al ., ; Cardoso et al ., ; Lamontagne et al ., ; Gonzalez et al ., ; Mancilla et al ., ; Zhang et al ., ; Tian et al ., ; Dabral et al ., ; Salvador‐Bescos et al ., ); mutations in this gene set result in a rough phenotype in Brucella melitensis (Gonzalez et al ., ). It is well established that B. ovis is a stably rough strain that lacks LPS O‐polysaccharide (Gonzalez et al ., ; Tsolis et al ., ; Soler‐Llorens et al ., ; Mancilla, ). Indeed, many of the O‐polysaccharide genes that are synthetically lethal with eipA in B. abortus are frame‐shifted, carry nonsense mutations, or are absent from the genome of B. ovis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus

Herrou

Willett

Fiebig

et al. 2019

Molecular Microbiology

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Summary Molecular components of the Brucella abortus cell envelope play a major role in its ability to infect, colonize and survive inside mammalian host cells. In this study, we have defined a role for a conserved gene of unknown function in B. abortus envelope stress resistance and infection. Expression of this gene, which we name eipA, is directly activated by the essential cell cycle regulator, CtrA. eipA encodes a soluble periplasmic protein that adopts an unusual eight‐stranded β‐barrel fold. Deletion of eipA attenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to treatments that compromise the cell envelope integrity. Transposon disruption of genes required for LPS O‐polysaccharide biosynthesis is synthetically lethal with eipA deletion. This genetic connection between O‐polysaccharide and eipA is corroborated by our discovery that eipA is essential in Brucella ovis, a naturally rough species that harbors mutations in several genes required for O‐polysaccharide production. Conditional depletion of eipA expression in B. ovis results in a cell chaining phenotype, providing evidence that eipA directly or indirectly influences cell division in Brucella. We conclude that EipA is a molecular determinant of Brucella virulence that functions to maintain cell envelope integrity and influences cell division.

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“…In Brucella , this phenomenon had been reported and was of great importance in basic and vaccine researches [ 34 ]. The phenotypic change of Brucella under natural conditions mainly existed in two ways: inserting fragments into genes and deletion of genes related to LPS synthesis [ 16 ]. In addition, studies had shown that changes in the expression levels of LPS-related genes also caused changes in the phenotype of Brucella [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing of rough Brucella melitensis in China provides insights into its genetic features

Yang

Piao

Mao

et al. 2020

Emerging Microbes & Infections

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Brucella spp. can cause the zoonosis brucellosis, which affects public health and safety and even economic development. B. melitensis has a smooth phenotype, while 28 B. melitensis isolates had a rough phenotype in 2018. In this study, rough phenotype detection and whole genome sequencing methods were used to analyze the genetic features of rough B. melitensis . A drug susceptibility test was also performed. The results showed that the rough B. melitensis strains originated from strains isolated in China rather than from foreign strains. Furthermore, an MS tree showed that 9 complexes to be epidemic in China. For the rough B. melitensis strains, expression of the metabolic function genes varied in the earlier stages of evolution compared to the cellular process and signalling function genes. Expression of some transcriptional regulatory factors also varied in the later stages of evolution, and compared to MFS transporter genes, ABC transporter genes varied in the earlier stages. Moreover, as there was no significant difference in rifampicin, doxycycline and streptomycin susceptibility between the smooth and rough B. melitensis strains, treatment of brucellosis was not affected by strain type. This study provided important information for understanding the genetics and evolution of rough B. melitensis in China.

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Smooth to Rough Dissociation in Brucella: The Missing Link to Virulence

Cited by 26 publications

References 64 publications

Periplasmic protein EipA determines envelope stress resistance and virulence inBrucella abortus

Periplasmic protein EipA determines envelope stress resistance and virulence inBrucella abortus

Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus

Whole-genome sequencing of rough Brucella melitensis in China provides insights into its genetic features

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