Moraxella catarrhalis Expresses a Cardiolipin Synthase That Impacts Adherence to Human Epithelial Cells

Buskirk, Sean W.; Lafontaine, Eric R.

doi:10.1128/jb.00298-13

Cited by 9 publications

(9 citation statements)

References 78 publications

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“…This group contains both eukaryotic and prokaryotic enzymes of phospholipid synthesis and modification [ 29 , 30 ]. The highly conserved amino acids of the HKD-motifs [HXK(X) 4 D(X) 6 G(X) 2 N] are crucial for enzyme activity [ 13 , 16 , 31 ] and are thought to form a single active site [ 32 ]. Additionally, A .…”

Section: Resultsmentioning

confidence: 99%

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Two Distinct Cardiolipin Synthases Operate in Agrobacterium tumefaciens

et al. 2016

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Cardiolipin (CL) is a universal component of energy generating membranes. In most bacteria, it is synthesized via the condensation of two molecules phosphatidylglycerol (PG) by phospholipase D-type cardiolipin synthases (PLD-type Cls). In the plant pathogen and natural genetic engineer Agrobacterium tumefaciens CL comprises up to 15% of all phospholipids in late stationary growth phase. A. tumefaciens harbors two genes, atu1630 (cls1) and atu2486 (cls2), coding for PLD-type Cls. Heterologous expression of either cls1 or cls2 in Escherichia coli resulted in accumulation of CL supporting involvement of their products in CL synthesis. Expression of cls1 and cls2 in A. tumefaciens is constitutive and irrespective of the growth phase. Membrane lipid profiling of A. tumefaciens mutants suggested that Cls2 is required for CL synthesis at early exponential growth whereas both Cls equally contribute to CL production at later growth stages. Contrary to many bacteria, which suffer from CL depletion, A. tumefaciens tolerates large changes in CL content since the CL-deficient cls1/cls2 double mutant showed no apparent defects in growth, stress tolerance, motility, biofilm formation, UV-stress and tumor formation on plants.

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Section: Resultsmentioning

confidence: 99%

“…In contrast, contribution of CL to virulence has been demonstrated in a number of human pathogens such as Moraxella catarrhalis , S . aureus and Salmonella enterica [ 10 , 31 , 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Two Distinct Cardiolipin Synthases Operate in Agrobacterium tumefaciens

et al. 2016

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“…The preferential localization of CL to the cell pole presumably accounts for the polar localization of some proteins in E. coli, such as the osmotic stress protein ProP (45) and the CL synthase ClsA (44). While ProP and ClsA are inner membrane proteins, CL also has an apparent role in the polar localization of the outer membrane protein IcsA in Shigella flexneri (46) and is hypothesized to play a role in the localization or display of adhesion proteins in the outer membrane of Moraxella catarrhalis (47). It is possible that FlgI fails to localize to the cell pole in the absence of normal levels of CL or specific CL species in H. pylori G27.…”

Section: Discussionmentioning

confidence: 99%

Loss of a Cardiolipin Synthase in Helicobacter pylori G27 Blocks Flagellum Assembly

et al. 2019

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Helicobacter pylori uses a cluster of polar, sheathed flagella for motility, which it requires for colonization of the gastric epithelium in humans. As part of a study to identify factors that contribute to localization of the flagella to the cell pole, we disrupted a gene encoding a cardiolipin synthase (clsC) in H. pylori strains G27 and B128. Flagellum biosynthesis was abolished in the H. pylori G27 clsC mutant but not in the B128 clsC mutant. Transcriptome sequencing analysis showed that flagellar genes encoding proteins needed early in flagellum assembly were expressed at wild-type levels in the G27 clsC mutant. Examination of the G27 clsC mutant by cryo-electron tomography indicated the mutant assembled nascent flagella that contained the MS ring, C ring, flagellar protein export apparatus, and proximal rod. Motile variants of the G27 clsC mutant were isolated after allelic exchange mutagenesis using genomic DNA from the B128 clsC mutant as the donor. Genome resequencing of seven motile G27 clsC recipients revealed that each isolate contained the flgI (encodes the P-ring protein) allele from B128. Replacing the flgI allele in the G27 clsC mutant with the B128 flgI allele rescued flagellum biosynthesis. We postulate that H. pylori G27 FlgI fails to form the P ring when cardiolipin levels in the cell envelope are low, which blocks flagellum assembly at this point. In contrast, H. pylori B128 FlgI can form the P ring when cardiolipin levels are low and allows for the biosynthesis of mature flagella. IMPORTANCE H. pylori colonizes the epithelial layer of the human stomach, where it can cause a variety of diseases, including chronic gastritis, peptic ulcer disease, and gastric cancer. To colonize the stomach, H. pylori must penetrate the viscous mucous layer lining the stomach, which it accomplishes using its flagella. The significance of our research is identifying factors that affect the biosynthesis and assembly of the H. pylori flagellum, which will contribute to our understanding of motility in H. pylori, as well as other bacterial pathogens that use their flagella for host colonization.

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“…In M. catarrhalis , cardiolipin is required for proper bacterial attachment to human epithelial cells ( 53 ). It is hypothesized that cardiolipin is required for the localization or display of adhesion proteins.…”

Section: Discussionmentioning

confidence: 99%

Cardiolipin Synthesis and Outer Membrane Localization Are Required for Shigella flexneri Virulence

Rossi

Yum

Agaisse

et al. 2017

mBio

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Cardiolipin, an anionic phospholipid that resides at the poles of the inner and outer membranes, is synthesized primarily by the putative cardiolipin synthase ClsA in Shigella flexneri. An S. flexneri clsA mutant had no cardiolipin detected within its membrane, grew normally in vitro, and invaded cultured epithelial cells, but it failed to form plaques in epithelial cell monolayers, indicating that cardiolipin is required for virulence. The clsA mutant was initially motile within the host cell cytoplasm but formed filaments and lost motility during replication and failed to spread efficiently to neighboring cells. Mutation of pbgA, which encodes the transporter for cardiolipin from the inner membrane to the outer membrane, also resulted in loss of plaque formation. The S. flexneri pbgA mutant had normal levels of cardiolipin in the inner membrane, but no cardiolipin was detected in the outer membrane. The pbgA mutant invaded and replicated normally within cultured epithelial cells but failed to localize the actin polymerization protein IcsA properly on the bacterial surface and was unable to spread to neighboring cells. The clsA mutant, but not the pbgA mutant, had increased phosphatidylglycerol in the outer membrane. This appeared to compensate partially for the loss of cardiolipin in the outer membrane, allowing some IcsA localization in the outer membrane of the clsA mutant. We propose a dual function for cardiolipin in S. flexneri pathogenesis. In the inner membrane, cardiolipin is essential for proper cell division during intracellular growth. In the outer membrane, cardiolipin facilitates proper presentation of IcsA on the bacterial surface.

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Moraxella catarrhalis Expresses a Cardiolipin Synthase That Impacts Adherence to Human Epithelial Cells

Cited by 9 publications

References 78 publications

Two Distinct Cardiolipin Synthases Operate in Agrobacterium tumefaciens

Two Distinct Cardiolipin Synthases Operate in Agrobacterium tumefaciens

Loss of a Cardiolipin Synthase in Helicobacter pylori G27 Blocks Flagellum Assembly

Cardiolipin Synthesis and Outer Membrane Localization Are Required for Shigella flexneri Virulence

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