Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus

Voronin, Denis; Guimarães, Ana Flávia Bereta Coelho; Molyneux, Gemma; Johnston, Kelly L.; Ford, Louise; Taylor, Mark J.

doi:10.1186/s13071-014-0462-1

Cited by 18 publications

(7 citation statements)

References 46 publications

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“…1), which was significantly lower than the extent of upregulation due to Wolbachia infection (around 7-fold, P < 0.01). Voronin et al (2014) have shown that Wolbachia cell membrane contains the PGN-associated lipoprotein (PAL). PAL can specifically bind DAP (Parsons et al, 2006), indicating that DAP is present on the Wolbachia membrane.…”

Section: Discussionmentioning

confidence: 99%

Wolbachia‐induced expression of kenny gene in testes affects male fertility in Drosophila melanogaster

et al. 2019

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Wolbachia are Gram‐negative endosymbionts that are known to cause embryonic lethality when infected male insects mate with uninfected females or with females carrying a different strain of Wolbachia, a situation characterized as cytoplasmic incompatibility (CI). However, the mechanism of CI is not yet fully understood, although recent studies on Drosophila melanogaster have achieved great progress. Here, we found that Wolbachia infection caused changes in the expressions of several immunity‐related genes, including significant upregulation of kenny (key), in the testes of D. melanogaster. Overexpression of key in fly testes led to a significant decrease in egg hatch rates when these flies mate with wild‐type females. Wolbachia‐infected females could rescue this embryonic lethality. Furthermore, in key overexpressing testes terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling signal was significantly stronger than in the control testes, and the level of reactive oxygen species was significantly increased. Overexpression of key also resulted in alterations of some other immunity‐related gene expressions, including the downregulation of Zn72D. Knockdown of Zn72D in fly testes also led to a significant decrease in egg hatch rates. These results suggest that Wolbachia might induce the defect in male host fertility by immunity‐related pathways and thus cause an oxidative damage and cell death in male testes.

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Section: Discussionmentioning

confidence: 99%

Wolbachia‐induced expression of kenny gene in testes affects male fertility in Drosophila melanogaster

et al. 2019

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“…Hence, these data provide initial experimental evidence for an extracytoplasmic extended C-terminus in polytopic "extended VirB6-like proteins" in bacteria of the P-T4SS group. Moreover, antibodies reacting with VirB6-3 proteins from E. chaffeensis and Wolbachia species were detected in sera from dogs infected with E. chaffeensis (44) and in sera from humans infected with the filarial nematode Wuchereria bancrofti (38). This is additional evidence that in Rickettsiales this protein is not only surface exposed, but also induces immune responses.…”

Section: The Virb6-4::himar Mutant Has a Reduced Proliferation In Vitromentioning

confidence: 77%

“…Due to the C-terminal hydrophilic repeat domains of VirB6-3 and VirB6-4, the focus of this work, it has been proposed that these proteins or their C-terminal domains are surface exposed or proteolytically released into the host cell ( 15 ). In addition, evidence of surface exposure of the extended VirB6 proteins has been presented for other Rickettsiales ( 36 – 38 ). Hence, we confirmed their expression in infected HL-60 cells by Western immunoblotting and determined whether these proteins are surface exposed by trypsin digestion of intact A. phagocytophilum organisms.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the importance of lipoproteins in physiology, virulence, and host immune evasion, very little is known about their role in A. phagocytophilum . In other Rickettsiales , such as E. chaffeensis ( 44 ) and the Wolbachia symbiont of filarial nematodes ( 38 ), VirB6-3, but not VirB6-4, has also been identified as a putative lipoprotein. Moreover, antibodies reacting with VirB6-3 proteins from E. chaffeensis and Wolbachia species were detected in sera from dogs infected with E. chaffeensis ( 44 ) and in sera from humans infected with the filarial nematode Wuchereria bancrofti ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

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Disruption of VirB6 Paralogs in Anaplasma phagocytophilum Attenuates Its Growth

et al. 2020

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Many pathogenic bacteria translocate virulence factors into their eukaryotic hosts by means of Type 4 Secretion Systems (T4SS) spanning the inner and outer membranes. Genes encoding components of these systems have been identified within the Order Rickettsiales based upon their sequence similarities to other prototypical systems. Anaplasma phagocytophilum are obligate intracellular, tick-borne bacteria that are members of this Order. The organization of these components at the genomic level was determined in several Anaplasma phagocytophilum strains, showing overall conservation, with the exceptions of virB2 and virB6 genes. The virB6 loci are characterized by the presence of four virB6 copies (virB6-1 through virB6-4) arranged in tandem within a gene cluster known as the sodB-virBs operon. Interestingly, the virB6-4 gene varies significantly in length among different strains due to extensive tandem repeats at the 3′ end. To gain understanding of how these enigmatic virB6 genes function in A. phagocytophilum we investigated their expression in infected human and tick cells. Our results show that these genes are expressed by A. phagocytophilum replicating in both cell types, and that VirB6-3 and VirB6-4 proteins are surface-exposed. Analysis of an A. phagocytophilum mutant carrying the Himar1 transposon within the virB6-4 gene, demonstrated that the insertion not only disrupted its expression but also exerted a polar effect in the sodB-virBs operon. Moreover, the altered expression of genes within this operon was associated with the attenuated in vitro growth of A. phagocytophilum in human and tick cells, indicating the importance of these genes in the physiology of this obligate intracellular bacterium in such different environments. IMPORTANCE Knowledge of the T4SS is derived from model systems, such as Agrobacterium tumefaciens. The structure of the T4SS in Rickettsiales differs from the classical arrangement. These differences include missing and duplicated components with structural alterations. Particularly, two sequenced virB6-4 genes encode unusual C-terminal structural extensions resulting in proteins of 4322 (GenBank YYU_01815) and 9935 (P029_01630) amino acids. To understand how the T4SS is used in A. phagocytophilum we describe the expression of the virB6 paralogs and explore their role as the bacteria replicate within its host cell. Conclusions about the importance of these paralogs for colonization of human and tick cells is supported by the deficient phenotype of an A. phagocytophilum mutant isolated from a sequence-defined transposon insertion library.

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“…Recently PAL was confirmed by proteomics as one of the most abundant proteins in extracts from adult B . malayi female worms [20].…”

Section: Introductionmentioning

confidence: 99%

Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis

et al. 2019

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BackgroundLymphatic filariasis (LF) is a neglected tropical disease, and the Global Program to Eliminate LF delivers mass drug administration (MDA) to 500 million people every year. Adverse events (AEs) are common after LF treatment.Methodology/Principal findingsTo better understand the pathogenesis of AEs, we studied LF-patients from a treatment trial. Plasma levels of many filarial antigens increased post-treatment in individuals with AEs, and this is consistent with parasite death. Circulating immune complexes were not elevated in these participants, and the classical complement cascade was not activated. Multiple cytokines increased after treatment in persons with AEs. A transcriptomic analysis was performed for nine individuals with moderate systemic AEs and nine matched controls. Differential gene expression analysis identified a significant transcriptional signature associated with post-treatment AEs; 744 genes were upregulated. The transcriptional signature was enriched for TLR and NF-κB signaling. Increased expression of seven out of the top eight genes upregulated in persons with AEs were validated by qRT-PCR, including TLR2.Conclusions/SignificanceThis is the first global study of changes in gene expression associated with AEs after treatment of lymphatic filariasis. Changes in cytokines were consistent with prior studies and with the RNAseq data. These results suggest that Wolbachia lipoprotein is involved in AE development, because it activates TLR2-TLR6 and downstream NF-κB. Additionally, LPS Binding Protein (LBP, which shuttles lipoproteins to TLR2) increased post-treatment in individuals with AEs. Improved understanding of the pathogenesis of AEs may lead to improved management, increased MDA compliance, and accelerated LF elimination.

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Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus

Cited by 18 publications

References 46 publications

Wolbachia‐induced expression of kenny gene in testes affects male fertility in Drosophila melanogaster

Wolbachia‐induced expression of kenny gene in testes affects male fertility in Drosophila melanogaster

Disruption of VirB6 Paralogs in Anaplasma phagocytophilum Attenuates Its Growth

Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis

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