A New Model and Method for Understanding Wolbachia-Induced Cytoplasmic Incompatibility

Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts' reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging “locks” on sperm DNA of infected males, but can also provide matching “keys” in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions

Bidirectional incompatibility among divergent Wolbachia and incompatibility level differences among closely related Wolbachia in Nasonia

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Heredity 99 (2007): 278–287, doi:10.1038/sj.hdy.6800994.Most insect groups harbor obligate bacterial symbionts from the alphaproteobacterial genus Wolbachia. These bacteria alter insect reproduction in ways that enhance their cytoplasmic transmission. One of the most common alterations is cytoplasmic incompatibility (CI) - a post-fertilization modification of the paternal genome that renders embryos inviable or unable to complete diploid development in crosses between infected males and uninfected females or infected females harboring a different strain. The parasitic wasp species complex Nasonia (N. vitripennis, N. longicornis, and N. giraulti) harbor at least six different Wolbachia that cause cytoplasmic incompatibility. Each species have double infections with a representative from both the A and B Wolbachia subgroups. CI relationships of the A and B Wolbachia of N. longicornis with those of N. giraulti and N. vitripennis are investigated here. We demonstrate that all pairwise crosses between the divergent A strains are bidirectionally incompatible. We were unable to characterize incompatibility between the B Wolbachia, but we establish that the B strain of N. longicornis induces no or very weak CI in comparison to the closely related B strain in N. giraulti that expresses complete CI. Taken together with previous studies, we show that independent acquisition of divergent A Wolbachia has resulted in three mutually incompatible strains, while codivergence of B Wolbachia in N. longicornis and N. giraulti is associated with differences in CI level. Understanding the diversity and evolution of new incompatibility strains will contribute to a fuller understanding of Wolbachia invasion dynamics and Wolbachia-assisted speciation in certain groups of insects.This work was supported by grant EF-0328363 and DEB-9981634 from the National Science Foundation to J.H.W. and an Ernst Caspari Research Fellowship to S.R.B while he was at the University of Rochester. S.R.B. acknowledges support from the NASA Astrobiology Institute (NNA04CC04A)

The effects of, and interactions between, Cardinium and Wolbachia in the doubly infected spider mite Bryobia sarothamni (Acari: Tetranychidae)

Many arthropods are infected with vertically transmitted, intracellular bacteria manipulating their host's reproduction. Cytoplasmic incompatibility (CI) is commonly observed and is expressed as a reduction in the number of offspring in crosses between infected males and uninfected females (or females infected with a different bacterial strain). CI is often related to the presence of Wolbachia, but recent findings indicate that a second reproductive parasite, Cardinium, is also capable of inducing CI. Although both Wolbachia and Cardinium occur in arthropods and may infect the same host species, little is known about their interactions. We observed Wolbachia and Cardinium in the sexual spider mite Bryobia sarothamni (Acari: Tetranychidae) and investigated the effects of both bacteria on reproduction. We performed all possible crossing combinations using naturally infected strains, and show that Cardinium induces strong CI, expressed as an almost complete female mortality. B. sarothamni is the third host species in which Cardinium-induced CI is observed, and this study reveals the strongest CI effect found so far. Wolbachia, however, did not induce CI. Even so, CI was not induced by doubly infected males, and neither singly Wolbachia-infected nor doubly infected females could rescue CI induced by Cardinium-infected males. Possibly, this is related to the differences between Cardinium strains infecting singly and doubly infected individuals. We found a cost of infection in single infected individuals, but not in doubly infected individuals. We show that infection frequencies in field populations ranged from completely uninfected to a polymorphic state. In none of the populations infections were fixe

Superinfection of cytoplasmic incompatibility-inducing Wolbachia is not additive in Orius strigicollis (Hemiptera: Anthocoridae)

Cytoplasmic incompatibility (CI) allows the intracellular, maternally inherited bacterial symbiont Wolbachia to invade arthropod host populations by inducing infertility in crosses between infected males and uninfected females. The general pattern is consistent with a model of sperm modification, rescued only by egg cytoplasm infected with the same strain of symbiont. The predacious flower bug Orius strigicollis is superinfected with two strains of Wolbachia, wOus1 and wOus2. Typically, superinfections of CI Wolbachia are additive in their effects; superinfected males are incompatible with uninfected and singly infected females. In this study, we created an uninfected line, and lines singly infected with wOus1 and wOus2 by antibiotic treatment. Then, all possible crosses were conducted among the four lines. The results indicated that while wOus2 induces high levels of CI, wOus1 induces very weak or no CI, but can rescue CI caused by wOus2 to a limited extent. Levels of incompatibility in crosses with superinfected males did not show the expected pattern. In particular, superinfected males caused extremely weak CI when mated with either singly infected or uninfected females. An analysis of symbiont densities showed that wOus1 densities were significantly higher than wOus2 densities in superinfected males, and wOus2 densities were lower, but not significantly, in superinfected relative to singly infected males. These data lend qualified support for the hypothesis that wOus1 interferes with the ability of wOus2 to cause CI by suppressing wOus2 densities. To our knowledge, this is the first clear case of non-additive CI in a natural superinfection

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world’s largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ~30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death