Requirement of lipid II biosynthesis for cell division in cell wall-less Wolbachia, endobacteria of arthropods and filarial nematodes

Vollmer, Jennifer; Schiefer, Andrea; Schneider, Tanja; Jülicher, Karen; Johnston, Kelly L.; Taylor, Mark J.; Sahl, Hans‐Georg; Hoerauf, Achim; Pfarr, Kenneth

doi:10.1016/j.ijmm.2013.01.002

Cited by 39 publications

(68 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptidoglycans are not thought to be produced by Wolbachia [36,37], but are produced by Cardinium [36,38], and also by Rickettsia, albeit sometimes at very low levels [39,40]. Therefore, the low incidence in hexapods of Rickettsia and especially Cardinium, might be due to their eliciting an additional immune response, not found in chelicerates, and not induced by Wolbachia in any host group.…”

Section: Results (A) Estimating Symbiont Incidencementioning

confidence: 99%

The incidence of bacterial endosymbionts in terrestrial arthropods

et al. 2015

View full text Add to dashboard Cite

Intracellular endosymbiotic bacteria are found in many terrestrial arthropods and have a profound influence on host biology. A basic question about these symbionts is why they infect the hosts that they do, but estimating symbiont incidence (the proportion of potential host species that are actually infected) is complicated by dynamic or low prevalence infections. We develop a maximum-likelihood approach to estimating incidence, and testing hypotheses about its variation. We apply our method to a database of screens for bacterial symbionts, containing more than 3600 distinct arthropod species and more than 150 000 individual arthropods. After accounting for sampling bias, we estimate that 52% (CIs: 48-57) of arthropod species are infected with Wolbachia, 24% (CIs: 20-42) with Rickettsia and 13% (CIs: 13-55) with Cardinium. We then show that these differences stem from the significantly reduced incidence of Rickettsia and Cardinium in most hexapod orders, which might be explained by evolutionary differences in the arthropod immune response. Finally, we test the prediction that symbiont incidence should be higher in speciose host clades. But while some groups do show a trend for more infection in species-rich families, the correlations are generally weak and inconsistent. These results argue against a major role for parasitic symbionts in driving arthropod diversification.

show abstract

Section: Results (A) Estimating Symbiont Incidencementioning

confidence: 99%

The incidence of bacterial endosymbionts in terrestrial arthropods

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In particular, a subset of bacteria including the pathogens Francisella tularensis and Chlamydia trachomatis , possess a cell wall but do not encode aPBPs. Among these taxa are organisms recently discovered to make PG 32–35 or encode an essential lipid II biosynthetic pathway 36 . In all cases, these organisms contain at least one SEDS family member and a bPBP, and we hypothesize that the assembly of their cell wall is mediated by these enzymes.…”

Section: Discussionmentioning

confidence: 99%

SEDS proteins are a widespread family of bacterial cell wall polymerases

Meeske

Riley

Robins

et al. 2016

Nature

452

538

View full text Add to dashboard Cite

Summary Elongation of rod-shaped bacteria is mediated by a dynamic peptidoglycan synthetic machinery called the Rod complex. We report that in Bacillus subtilis this complex is functional in the absence of all known peptidoglycan polymerases. Cells lacking these enzymes survive by inducing an envelope stress response that increases expression of RodA, a widely conserved core component of the Rod complex. RodA is a member of the SEDS family of proteins that play essential but ill-defined roles in cell wall biogenesis during growth, division and sporulation. Our genetic and biochemical analyses indicate that SEDS proteins constitute a new family of peptidoglycan polymerases. Thus, B. subtilis and likely most bacteria use two distinct classes of polymerases to synthesize their exoskeleton. Our findings indicate that SEDS family proteins are core cell wall synthases of the cell elongation and division machinery, and represent attractive targets for antibiotic development.

show abstract

“…Peptidoglycan (PG) biosynthesis is one of the pathways within the bacteria which are essential for both cell division and cell wall elongation processes. Till date, only two reports are available on the functional attributes of the enzymes involved in PG synthesis in Wolbachia [18], [54]. In the current investigation, characterization of one of such enzyme i.e.…”

Section: Discussionmentioning

confidence: 97%

“…These have no mammalian counterpart and therefore present an attractive drug target. The annotated genome of Wolbachia reveals the presence of genes required for lipid ΙΙ precursors for PG biosynthesis including UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) [9], [18]. However, the role of lipid ΙΙ in Wolbachia remains unclear since other genes involved in PG synthesis such as those responsible for polymerization of glycans are absent.…”

Section: Introductionmentioning

confidence: 99%

“…It is well known that MurA catalyzes the first committed step in the cell wall biosynthesis of bacteria and transfers an enolpyruvyl group from phosphoenolpyruvate (PEP) to UDP-N-acetylglucosamine (UDPAG) to form UDP-N-acetylglucosamine enolpyruvate [19] which is a precursor to UDP-N-acetylmuramate, a requisite building block of bacterial cell wall (Figure 1) [20]. However, it has also been shown that inhibition of lipid II synthesis brings about a detrimental effect on Wolbachia within the insect cell lines [18]. The deletion/inactivation of MurA gene of Escherichia coli [21], Streptococcus pneumoniae [22], and Staphylococcus.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cloning, Expression and Characterization of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) from Wolbachia Endosymbiont of Human Lymphatic Filarial Parasite Brugia malayi

et al. 2014

View full text Add to dashboard Cite

Wolbachia, an endosymbiont of filarial nematode, is considered a promising target for treatment of lymphatic filariasis. Although functional characterization of the Wolbachia peptidoglycan assembly has not been fully explored, the Wolbachia genome provides evidence for coding all of the genes involved in lipid II biosynthesis, a part of peptidoglycan biosynthesis pathway. UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is one of the lipid II biosynthesis pathway enzymes and it has inevitably been recognized as an antibiotic target. In view of the vital role of MurA in bacterial viability and survival, MurA ortholog from Wolbachia endosymbiont of Brugia malayi (wBm-MurA) was cloned, expressed and purified for further molecular characterization. The enzyme kinetics and inhibition studies were undertaken using fosfomycin. wBm-MurA was found to be expressed in all the major life stages of B. malayi and was immunolocalized in Wolbachia within the microfilariae and female adults by the confocal microscopy. Sequence analysis suggests that the amino acids crucial for enzymatic activity are conserved. The purified wBm-MurA was shown to possess the EPSP synthase (3-phosphoshikimate 1-carboxyvinyltransferase) like activity at a broad pH range with optimal activity at pH 7.5 and 37°C temperature. The apparent affinity constant (K m) for the substrate UDP-N-acetylglucosamine was found to be 0.03149 mM and for phosphoenolpyruvate 0.009198 mM. The relative enzymatic activity was inhibited ∼2 fold in presence of fosfomycin. Superimposition of the wBm-MurA homology model with the structural model of Haemophilus influenzae (Hi-MurA) suggests binding of fosfomycin at the same active site. The findings suggest wBm-MurA to be a putative antifilarial drug target for screening of novel compounds.

show abstract

Requirement of lipid II biosynthesis for cell division in cell wall-less Wolbachia, endobacteria of arthropods and filarial nematodes

Cited by 39 publications

References 54 publications

The incidence of bacterial endosymbionts in terrestrial arthropods

The incidence of bacterial endosymbionts in terrestrial arthropods

SEDS proteins are a widespread family of bacterial cell wall polymerases

Cloning, Expression and Characterization of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) from Wolbachia Endosymbiont of Human Lymphatic Filarial Parasite Brugia malayi

Contact Info

Product

Resources

About