Phosphatidylethanolamine Synthesis Is Required for Optimal Virulence of
            <i>Brucella abortus</i>

Bukata, Lucas; Altabe, Silvia; Mendoza, Diego de; Ugalde, Rodolfo A.; Comerci, Diego J.

doi:10.1128/jb.01069-08

Cited by 39 publications

(43 citation statements)

References 35 publications

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“…Previous work on Brucella abortus demonstrated that disruption of the individual synthesis pathways for either PC (pcs and pmtA) (29) or PE (pssA) (17) resulted in reduced fitness of B. abortus strains in vitro and in vivo (17), demonstrating that the phospholipid composition of the envelope is critical to the biology of this organism. Our results detail a mechanism by which B. melitensis maintains a low abundance of PE in the cell envelope via expression of the BveA phospholipase A1 enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Two-dimensional thin-layer chromatography (2D-TLC) was performed on silica gel plates (Kieselgel 60; Merck) loaded with equal amounts of lipid preparations using the solvent chloroform-methanol-water (14:6:1) followed by chloroform-methanol-acetic acid (13:5:2). The phospholipids were identified with a molybdatophosphoric acid spray solution (Merck) and commercial standards (Avanti) (17). The relative amounts of the known membrane lipids were estimated by densitometry of stained 2D-TLC spots using a gray-scale, 8-bit transformed picture of the stained TLC plates with the BioSpectrum AC imaging system (UVP) and the densitometry tool of the Labworks software suite.…”

Section: Methodsmentioning

confidence: 99%

“…The apparent specificity of BveA for PE suggested that it targets PE in the B. melitensis cell envelope. To test this idea, we compared the relative amounts of the major membrane lipid species in the methyl-tert-butyl ether (MTBE) extracts of the B. melitensis wild type (16M), the bveA mutant (CMR27), and the chromosomally restored bveA mutant (TOK09; bveA restored ) by two-dimensional thin-layer chromatography (2D-TLC), using the conditions reported previously (17). The abundances of the main membrane lipids PC, PE, ornithine lipids (OL), PG, and cardiolipin (CL) were determined.…”

Section: B Melitensismentioning

confidence: 99%

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Phospholipase A1 Modulates the Cell Envelope Phospholipid Content of Brucella melitensis, Contributing to Polymyxin Resistance and Pathogenicity

Kerrinnes

Young

León

et al. 2015

Antimicrob Agents Chemother

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A subset of bacterial pathogens, including the zoonotic Brucella species, are highly resistant against polymyxin antibiotics. Bacterial polymyxin resistance has been attributed primarily to the modification of lipopolysaccharide; however, it is unknown what additional mechanisms mediate high-level resistance against this class of drugs. This work identified a role for the Brucella melitensis gene bveA (BMEII0681), encoding a predicted esterase, in the resistance of B. melitensis to polymyxin B. Characterization of the enzymatic activity of BveA demonstrated that it is a phospholipase A1 with specificity for phosphatidylethanolamine (PE). Further, lipidomic analysis of B. melitensis revealed an excess of PE lipids in the bacterial membranes isolated from the bveA mutant. These results suggest that by lowering the PE content of the cell envelope, BveA increases the resistance of B. melitensis to polymyxin B. BveA was required for survival and replication of B. melitensis in macrophages and for persistent infection in mice. BveA family esterases are encoded in the genomes of the alphaproteobacterial species that coexist with the polymyxin-producing bacteria in the rhizosphere, suggesting that maintenance of a low PE content in the bacterial cell envelope may be a shared persistence strategy for association with plant and mammalian hosts.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: B Melitensismentioning

confidence: 99%

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Phospholipase A1 Modulates the Cell Envelope Phospholipid Content of Brucella melitensis, Contributing to Polymyxin Resistance and Pathogenicity

Kerrinnes

Young

León

et al. 2015

Antimicrob Agents Chemother

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“…The role of PCS in Brucella pathogenicity was reported by Comerci et al [30], who showed that B. abortus possessing a pcs mutation display a reproducible virulence defect in mice. As the phospholipid composition of the membrane is critical for the interaction of B. abortus with the host cell [31], the Rev.1 pcs mutation may contribute to its attenuation.…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis of the original Elberg Brucella melitensis Rev.1 vaccine strain reveals insights into virulence attenuation

2018

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The live attenuated Brucella melitensis Rev.1 Elberg-originated vaccine strain has been widely used to control brucellosis in small ruminants. However, despite extensive research, the molecular mechanisms underlying the attenuation of this strain are still unknown. In the current study, we conducted a comprehensive comparative analysis of the whole-genome sequence of Rev.1 against that of the virulent reference strain, B. melitensis 16M. This analysis revealed five regions of insertion and three regions of deletion within the Rev.1 genome, among which, one large region of insertion, comprising 3,951 bp, was detected in the Rev.1 genome. In addition, we found several missense mutations within important virulence-related genes, which may be used to determine the mechanism underlying virulence attenuation. Collectively, our findings provide new insights into the Brucella virulence mechanisms and, therefore, may serve as a basis for the rational design of new Brucella vaccines.

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“…Some members of the PLD superfamily have been shown to affect bacterial adherence to epithelial cells (26,66). Alteration of the levels of PLs, specifically, PE, has been shown to result in a reduction in virulence-associated traits (67,68). To date, no CLS has been associated with adherence or virulence in general.…”

Section: Depicts the Structural Features Identified In Mclsmentioning

confidence: 99%

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

Buskirk

Lafontaine

2013

Journal of Bacteriology

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The major phospholipid constituents of Moraxella catarrhalis membranes are phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin (CL). However, very little is known regarding the synthesis and function of these phospholipids in M. catarrhalis. In this study, we discovered that M. catarrhalis expresses a cardiolipin synthase (CLS), termed MclS, that is responsible for the synthesis of CL within the bacterium. The nucleotide sequence of mclS is highly conserved among M. catarrhalis isolates and is predicted to encode a protein with significant amino acid similarity to the recently characterized YmdC/ClsC protein of Escherichia coli. Isogenic mclS mutant strains were generated in M. catarrhalis isolates O35E, O12E, and McGHS1 and contained no observable levels of CL. Site-directed mutagenesis of a highly conserved HKD motif of MclS also resulted in a CL-deficient strain. Moraxella catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. The reduction in adherence appears to be attributed to the absence of CL. These findings mark the first instance in which a CLS has been related to a virulence-associated trait. Moraxella catarrhalis is a human-specific pathogen of the mucosa and the causative agent of otitis media in children and respiratory infections in adults. After only nontypeable Haemophilus influenzae (NTHi) (ϳ26%) and Streptococcus pneumoniae (ϳ23%), M. catarrhalis is a leading bacterial cause of otitis media in children, being responsible for up to 20% of cases (1-4). Nearly 70% of infants are colonized by M. catarrhalis within their first 12 months of life (5). Moraxella catarrhalis is also the second leading cause of bacterial exacerbations of chronic obstructive pulmonary disease (COPD), being responsible for approximately 10% of cases (6). In the United States, COPD currently stands as the fourth leading cause of death (7). Exacerbations of COPD due to M. catarrhalis are responsible for an estimated $2 billion in medical costs and health care each year (8).Currently, there is no licensed vaccine available to prevent M. catarrhalis infection. A vaccine is desirable, however, due to the high prevalence, antibiotic resistance, and financial burden associated with M. catarrhalis infection. The vast majority of clinical isolates of M. catarrhalis (Ͼ95%) are now resistant to the ␤-lactamase family of antibiotics that was once considered a front-line treatment for the disease (9). This antibiotic resistance was acquired rapidly over a 10-to 15-year period in which the resistance spread from a few isolates to the majority (10-12). In addition, the incidence and prevalence of disease due to M. catarrhalis infection are expected to increase in the United States following the introduction of vaccines against the upper respiratory tract pathogens S. pneumoniae and NTHi (13). Finally, a vaccine to protect against the top three cau...

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Phosphatidylethanolamine Synthesis Is Required for Optimal Virulence of Brucella abortus

Cited by 39 publications

References 35 publications

Phospholipase A1 Modulates the Cell Envelope Phospholipid Content of Brucella melitensis, Contributing to Polymyxin Resistance and Pathogenicity

Phospholipase A1 Modulates the Cell Envelope Phospholipid Content of Brucella melitensis, Contributing to Polymyxin Resistance and Pathogenicity

Genomic analysis of the original Elberg Brucella melitensis Rev.1 vaccine strain reveals insights into virulence attenuation

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

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