scholarly journals The Biochemistry of Cytoplasmic Incompatibility Caused by Endosymbiotic Bacteria

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 852
Author(s):  
Hongli Chen ◽  
Mengwen Zhang ◽  
Mark Hochstrasser

Many species of arthropods carry maternally inherited bacterial endosymbionts that can influence host sexual reproduction to benefit the bacterium. The most well-known of such reproductive parasites is Wolbachia pipientis. Wolbachia are obligate intracellular α-proteobacteria found in nearly half of all arthropod species. This success has been attributed in part to their ability to manipulate host reproduction to favor infected females. Cytoplasmic incompatibility (CI), a phenomenon wherein Wolbachia infection renders males sterile when they mate with uninfected females, but not infected females (the rescue mating), appears to be the most common. CI provides a reproductive advantage to infected females in the presence of a threshold level of infected males. The molecular mechanisms of CI and other reproductive manipulations, such as male killing, parthenogenesis, and feminization, have remained mysterious for many decades. It had been proposed by Werren more than two decades ago that CI is caused by a Wolbachia-mediated sperm modification and that rescue is achieved by a Wolbachia-encoded rescue factor in the infected egg. In the past few years, new research has highlighted a set of syntenic Wolbachia gene pairs encoding CI-inducing factors (Cifs) as the key players for the induction of CI and its rescue. Within each Cif pair, the protein encoded by the upstream gene is denoted A and the downstream gene B. To date, two types of Cifs have been characterized based on the enzymatic activity identified in the B protein of each protein pair; one type encodes a deubiquitylase (thus named CI-inducing deubiquitylase or cid), and a second type encodes a nuclease (named CI-inducing nuclease or cin). The CidA and CinA proteins bind tightly and specifically to their respective CidB and CinB partners. In transgenic Drosophila melanogaster, the expression of either the Cid or Cin protein pair in the male germline induces CI and the expression of the cognate A protein in females is sufficient for rescue. With the identity of the Wolbachia CI induction and rescue factors now known, research in the field has turned to directed studies on the molecular mechanisms of CI, which we review here.

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 2029-2038 ◽  
Author(s):  
Jason L Rasgon ◽  
Thomas W Scott

AbstractBefore maternally inherited bacterial symbionts like Wolbachia, which cause cytoplasmic incompatibility (CI; reduced hatch rate) when infected males mate with uninfected females, can be used in a program to control vector-borne diseases it is essential to understand their dynamics of infection in natural arthropod vector populations. Our study had four goals: (1) quantify the number of Wolbachia strains circulating in the California Culex pipiens species complex, (2) investigate Wolbachia infection frequencies and distribution in natural California populations, (3) estimate the parameters that govern Wolbachia spread among Cx. pipiens under laboratory and field conditions, and (4) use these values to estimate equilibrium levels and compare predicted infection prevalence levels to those observed in nature. Strain-specific PCR, wsp gene sequencing, and crossing experiments indicated that a single Wolbachia strain infects Californian Cx. pipiens. Infection frequency was near or at fixation in all populations sampled for 2 years along a >1000-km north-south transect. The combined statewide infection frequency was 99.4%. Incompatible crosses were 100% sterile under laboratory and field conditions. Sterility decreased negligibly with male age in the laboratory. Infection had no significant effect on female fecundity under laboratory or field conditions. Vertical transmission was >99% in the laboratory and ∼98.6% in the field. Using field data, models predicted that Wolbachia will spread to fixation if infection exceeds an unstable equilibrium point above 1.4%. Our estimates accurately predicted infection frequencies in natural populations. If certain technical hurdles can be overcome, our data indicate that Wolbachia can invade vector populations as part of an applied transgenic strategy for vector-borne disease reduction.


2017 ◽  
Vol 114 (23) ◽  
pp. 6110-6115 ◽  
Author(s):  
Shun-ichiro Takano ◽  
Midori Tuda ◽  
Keiji Takasu ◽  
Naruto Furuya ◽  
Yuya Imamura ◽  
...  

Maternally inherited bacterial endosymbionts in arthropods manipulate host reproduction to increase the fitness of infected females. Cytoplasmic incompatibility (CI) is one such manipulation, in which uninfected females produce few or no offspring when they mate with infected males. To date, two bacterial endosymbionts,WolbachiaandCardinium, have been reported as CI inducers. OnlyWolbachiainduces complete CI, which causes 100% offspring mortality in incompatible crosses. Here we report a third CI inducer that belongs to a unique clade of Alphaproteobacteria detected within the coconut beetle,Brontispa longissima. This beetle comprises two cryptic species, the Asian clade and the Pacific clade, which show incompatibility in hybrid crosses. Different bacterial endosymbionts, a unique clade of Alphaproteobacteria in the Pacific clade andWolbachiain the Asian clade, induced bidirectional CI between hosts. The former induced complete CI (100% mortality), whereas the latter induced partial CI (70% mortality). Illumina MiSeq sequencing and denaturing gradient gel electrophoresis patterns showed that the predominant bacterium detected in the Pacific clade ofB. longissimawas this unique clade of Alphaproteobacteria alone, indicating that this endosymbiont was responsible for the complete CI. Sex distortion did not occur in any of the tested crosses. The 1,160 bp of 16S rRNA gene sequence obtained for this endosymbiont had only 89.3% identity with that ofWolbachia, indicating that it can be recognized as a distinct species. We discuss the potential use of this bacterium as a biological control agent.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Sarah B Mueller ◽  
Susan B Gurley ◽  
Christopher D Kontos

Disruptions in the function of the quiescent endothelial cells (ECs) that line mature vessels can both result in and contribute to the progression of numerous cardiovascular diseases including hypertension, atherosclerosis, and disorders of vascular permeability. Despite recent attention, the signaling pathways that are active in quiescent ECs remain poorly characterized relative to those that regulate EC activation. In an effort to provide mechanistic insight into these pathways, we have characterized the previously undescribed protein Caskin2, which we hypothesize is a novel regulator of EC quiescence. Caskin2 is expressed in ECs throughout the vasculature, including the aorta, coronary arteries, and renal glomeruli. In vitro, Caskin2 promotes a quiescent EC phenotype characterized by decreased proliferation and increased resistance to apoptosis-inducing factors. Caskin2 knockout mice are viable and fertile. However, preliminary radiotelemetry measurements indicate that Caskin2 knockout (KO) mice have mildly elevated systemic blood pressure (BP). Compared to wild type (WT) littermates (n=8), Caskin2 KO mice (n=7) had increased mean arterial pressure (119+/-1 vs. 113+/-1, p=0.012), systolic BP (138+/-2 vs. 132+/-2, p=0.023), and diastolic BP (99+/-1 vs. 93+/-1, p=0.014) at baseline. To explore the molecular mechanisms of Caskin2’s effects, we used mass spectrometry to identify interacting proteins. Among the 67 proteins identified were the Ser/Thr phosphatase protein phosphatase 1 (PP1) and eNOS. Using standard in vitro biochemical techniques, we demonstrated that Caskin2 acts as a PP1 regulatory subunit. Interestingly, homologous expression of Caskin2 in vitro resulted in a marked increase in phosphorylation of eNOS on S1177, which is known to promote eNOS activity, and a decrease in phosphorylation on T495, which is associated with eNOS inhibition. Finally, PP1 has been shown to dephosphorylate eNOS T495 in vitro, suggesting a molecular mechanism for our in vivo findings. Ongoing work aims to determine if the interaction of Caskin2 and PP1 is required for the Caskin2-induced increase in activating phosphorylation of eNOS and to characterize the physiological mechanisms responsible for Caskin2’s effects on BP in more detail.


Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1162 ◽  
Author(s):  
Christine J. Ye ◽  
Zachary Sharpe ◽  
Henry H. Heng

When discussing chromosomal instability, most of the literature focuses on the characterization of individual molecular mechanisms. These studies search for genomic and environmental causes and consequences of chromosomal instability in cancer, aiming to identify key triggering factors useful to control chromosomal instability and apply this knowledge in the clinic. Since cancer is a phenomenon of new system emergence from normal tissue driven by somatic evolution, such studies should be done in the context of new genome system emergence during evolution. In this perspective, both the origin and key outcome of chromosomal instability are examined using the genome theory of cancer evolution. Specifically, chromosomal instability was linked to a spectrum of genomic and non-genomic variants, from epigenetic alterations to drastic genome chaos. These highly diverse factors were then unified by the evolutionary mechanism of cancer. Following identification of the hidden link between cellular adaptation (positive and essential) and its trade-off (unavoidable and negative) of chromosomal instability, why chromosomal instability is the main player in the macro-cellular evolution of cancer is briefly discussed. Finally, new research directions are suggested, including searching for a common mechanism of evolutionary phase transition, establishing chromosomal instability as an evolutionary biomarker, validating the new two-phase evolutionary model of cancer, and applying such a model to improve clinical outcomes and to understand the genome-defined mechanism of organismal evolution.


Author(s):  
Nouhayla Hafidi ◽  
Abdellah El Barkany ◽  
Morad Mahmoudi

This article addresses the problem of the joint policy of production and maintenance under constraint of outsourcing. The production system considered brings together two companies; the principal represented by a machine Md, while the subcontractor represented by a machine Ms. Our production system aims to satisfy a constant and continuous demand for a single product type. Indeed, outsourcing is justified by the lack of production capacity. However, the main objective is to determine simultaneously for each period, the age of preventive maintenance, the optimal stock threshold level, the maximum capacity of subcontractor and its unit cost of production, to better satisfy the customer's need. The last two parameters encourage an optimal choice of subcontractor, while minimizing the total cost generated by the contractor, including the costs of maintenance, production, storage and shortage. The results show that the proposed model performs quite well and opens new research direction for future improvements.


2006 ◽  
Vol 273 (1593) ◽  
pp. 1455-1458 ◽  
Author(s):  
Fleur E Champion de Crespigny ◽  
Nina Wedell

The maternally inherited bacterium Wolbachia pipientis imposes significant fitness costs on its hosts. One such cost is decreased sperm production resulting in reduced fertility of male Drosophila simulans infected with cytoplasmic incompatibility (CI) inducing Wolbachia . We tested the hypothesis that Wolbachia infection affects sperm competitive ability and found that Wolbachia infection is indeed associated with reduced success in sperm competition in non-virgin males. In the second male role, infected males sired 71% of the offspring whereas uninfected males sired 82% of offspring. This is the first empirical evidence indicating that Wolbachia infection deleteriously affects sperm competition and raises the possibility that polyandrous females can utilize differential sperm competitive ability to bias the paternity of broods and avoid the selfish manipulations of Wolbachia . This suggests a relationship between Wolbachia infection and host reproductive strategies. These findings also have important consequences for Wolbachia population dynamics because the transmission advantage of Wolbachia is likely to be undermined by sperm competition.


2012 ◽  
Vol 22 (Supp 2) ◽  
pp. S45-S57 ◽  
Author(s):  
Francesmary Modugno ◽  
Robert P. Edwards

ObjectiveTo review the current understanding of the underlying molecular, biologic, and genetic mechanisms involved in ovarian cancer development and how these mechanisms can be targets for prevention, detection, and treatment of the disease and its recurrence.MethodsIn May 2012, we convened a meeting of researchers, clinicians, and consumer advocates to review the state of current knowledge on molecular mechanisms and identify fruitful areas for further investigations.ResultsThe meeting consisted of 7 scientific sessions ranging from Epidemiology, Early Detection, and Biology to Therapeutics and Quality of Life. Sessions consisted of talks and panel discussions by international leaders in ovarian cancer research. A special career development session by the Congressionally Directed Medical Research Program Department of Defense Ovarian Cancer Academy as well as an oral abstract and poster session showcased promising new research by junior scientists.ConclusionsTechnological advances in the last decade have increased our knowledge of the molecular mechanisms involved in a host of biological activities related to ovarian cancer. Understanding the role these mechanisms play in cancer initiation and progression will help lead to the development of prevention and treatment modalities that can be personalized to each patient, thereby helping to overcome this highly fatal malignancy.


Genomic instability is a major threat to living organisms. To counteract the damaging effects posed by endogenous and environmental agents, such as chemicals or radiation, micro-organisms devote several percent of their genome to encode proteins that function in the repair and recombination of DNA. For many years, a relatively small group of scientists have carefully delineated the molecular mechanisms of these repair processes, using the simplest model systems available, namely Escherichia coli and Saccharomyces cerevisiae . These studies, which until recently had only moderate impact outside of the field, now provide the cornerstone for exciting new research into analogous processes in hum an cells. The reason for this is the revelation that the biochemical pathways for the accurate replication, repair and recombination of DNA have been conserved through evolution.


Insects ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 788
Author(s):  
Xuefen Xu ◽  
Peter M. Ridland ◽  
Paul A. Umina ◽  
Alex Gill ◽  
Perran A. Ross ◽  
...  

The maternally inherited endosymbiont, Wolbachia pipientis, plays an important role in the ecology and evolution of many of its hosts by affecting host reproduction and fitness. Here, we investigated 13 dipteran leaf-mining species to characterize Wolbachia infections and the potential for this endosymbiont in biocontrol. Wolbachia infections were present in 12 species, including 10 species where the Wolbachia infection was at or near fixation. A comparison of Wolbachia relatedness based on the wsp/MLST gene set showed that unrelated leaf-mining species often shared similar Wolbachia, suggesting common horizontal transfer. We established a colony of Liriomyza brassicae and found adult Wolbachia density was stable; although Wolbachia density differed between the sexes, with females having a 20-fold higher density than males. Wolbachia density increased during L. brassicae development, with higher densities in pupae than larvae. We removed Wolbachia using tetracycline and performed reciprocal crosses between Wolbachia-infected and uninfected individuals. Cured females crossed with infected males failed to produce offspring, indicating that Wolbachia induced complete cytoplasmic incompatibility in L. brassicae. The results highlight the potential of Wolbachia to suppress Liriomyza pests based on approaches such as the incompatible insect technique, where infected males are released into populations lacking Wolbachia or with a different incompatible infection.


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