A Eukaryote-like Cardiolipin Synthase Is Present in Streptomyces coelicolor and in Most Actinobacteria

Sandoval-Calderón, Mario; Geiger, Otto; Guan, Ziqiang; Barona‐Gómez, Francisco; Sohlenkamp, Christian

doi:10.1074/jbc.m109.006072

Cited by 48 publications

(61 citation statements)

References 54 publications

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“…The clsB gene product also catalyzes the formation of CL in E. coli, but its substrates have not been definitively established. In yeast (31), mammals (33), and actinobacteria (20), Cls (CRD1, hCLS1, and Sco1389 gene products, respectively) uses CDP-DAG and PG as substrates. The clsC gene product of E. coli catalyzes a third mode of CL synthesis, which is the subject of this report.…”

Section: Resultsmentioning

confidence: 99%

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Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates

Tan

Bogdanov²,

Zhao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Depending on growth phase and culture conditions, cardiolipin (CL) makes up 5-15% of the phospholipids in Escherichia coli with the remainder being primarily phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). In E. coli, the cls and ybhO genes (renamed clsA and clsB, respectively) each encode a CL synthase (Cls) that catalyzes the condensation of two PG molecules to form CL and glycerol. However, a ΔclsAB mutant still makes CL in the stationary phase, indicating the existence of additional Cls. We identified a third Cls encoded by ymdC (renamed clsC). ClsC has sequence homology with ClsA and ClsB, which all belong to the phospholipase D superfamily. The ΔclsABC mutant lacks detectible CL regardless of growth phase or growth conditions. CL can be restored to near wild-type levels in stationary phase in the triple mutant by expressing either clsA or clsB. Expression of clsC alone resulted in a low level of CL in the stationary phase, which increased to near wild-type levels by coexpression of its neighboring gene, ymdB. CL synthesis by all Cls is increased with increasing medium osmolarity during logarithmic growth and in stationary phase. However, only ClsA contributes detectible levels of CL at low osmolarity during logarithmic growth. Mutation of the putative catalytic motif of ClsC prevents CL formation. Unlike eukaryotic Cls (that use PG and CDP-diacylglycerol as substrates) or ClsA, the combined YmdB-ClsC used PE as the phosphatidyl donor to PG to form CL, which demonstrates a third and unique mode for CL synthesis.cardiolipin-deficient | bacteria | mass spectrometry

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Section: Resultsmentioning

confidence: 99%

“…1). A cls gene found in Streptomyces coelicolor and in most actinobacteria was recently shown to possess a CDP-DAG-dependent Cls (20). Based solely on informatics analysis, Trypanosoma brucei was suggested to encode a bacterial-type Cls (1).…”

mentioning

confidence: 99%

Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates

Tan

Bogdanov²,

Zhao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

212

321

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“…After incubation for 1 day at 50°C in proteinase K buffer (100 mM EDTA [pH 8], 0.2% deoxycholate, 0.1% N-lauroyl-sarcosine, and 50 g ml Ϫ1 of proteinase K), the plugs were washed three times for 20 min each time in washing buffer. Gel electrophoresis was done in a Bio-Rad CHEF-DRIII system under the following conditions: one-sixth of the plug; initial switch time (IS), 800 s; final switch time (FS), 800 s; temperature, 13.5°C; field angle,106°; run time, 64 h at 2.2 V cm ; Amersham Biosciences) for 24 h. Lipids were extracted, and the chloroform phase was subjected to lipid analysis in onedimensional thin-layer chromatography (TLC) plates (high-performance TLC aluminum sheets, Silica Gel 60; Merck) using a chloroform-methanol-glacial acetic acid solvent system as described previously (52).…”

Section: Methodsmentioning

confidence: 99%

Plasmids with a Chromosome-Like Role in Rhizobia

et al. 2011

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Replicon architecture in bacteria is commonly comprised of one indispensable chromosome and several dispensable plasmids. This view has been enriched by the discovery of additional chromosomes, identified mainly by localization of rRNA and/or tRNA genes, and also by experimental demonstration of their requirement for cell growth. The genome of Rhizobium etli CFN42 is constituted by one chromosome and six large plasmids, ranging in size from 184 to 642 kb. Five of the six plasmids are dispensable for cell viability, but plasmid p42e is unusually stable. One possibility to explain this stability would be that genes on p42e carry out essential functions, thus making it a candidate for a secondary chromosome. To ascertain this, we made an in-depth functional analysis of p42e, employing bioinformatic tools, insertional mutagenesis, and programmed deletions. Nearly 11% of the genes in p42e participate in primary metabolism, involving biosynthetic functions (cobalamin, cardiolipin, cytochrome o, NAD, and thiamine), degradation (asparagine and melibiose), and septum formation (minCDE). Synteny analysis and incompatibility studies revealed highly stable replicons equivalent to p42e in content and gene order in other Rhizobium species. A systematic deletion analysis of p42e allowed the identification of two genes (RHE_PE00001 and RHE_PE00024), encoding, respectively, a hypothetical protein with a probable winged helix-turn-helix motif and a probable two-component sensor histidine kinase/response regulator hybrid protein, which are essential for growth in rich medium. These data support the proposal that p42e and its homologous replicons (pA, pRL11, pRLG202, and pR132502) merit the status of secondary chromosomes.

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“…Eukaryotic-type CLSs synthesize CL from one molecule of CDP-diacylglycerol and one molecule of phosphatidylglycerol (PG). Though expressed predominantly in eukaryotes, eukaryotictype CLSs are also expressed by Streptomyces coelicolor and most actinobacteria (33). The eukaryotic-type CLS is not a member of the PLD superfamily, unlike the other two types of CLSs.…”

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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...

show abstract

A Eukaryote-like Cardiolipin Synthase Is Present in Streptomyces coelicolor and in Most Actinobacteria

Cited by 48 publications

References 54 publications

Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates

Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates

Plasmids with a Chromosome-Like Role in Rhizobia

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

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