The Biochemistry of Cytoplasmic Incompatibility Caused by Endosymbiotic Bacteria

Abstract

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.

Cardinium Localization During Its Parasitoid Wasp Host’s Development Provides Insights Into Cytoplasmic Incompatibility

“…and Sullivan, 2002;Poinsot et al, 2003;Bossan et al, 2011;Beckmann et al, 2019a;Chen et al, 2020;Shropshire et al, 2020). The two models differ in whether the mature sperm cells harbor a Cardinium-derived CI effector (a stockpiling method, or the "toxin-antidote" or "lock-and-key" model in the language of the Wolbachia CI literature; Hurst, 1991;Poinsot et al, 2003;Beckmann et al, 2019a;Chen et al, 2020) or not (a direct alteration method or the "host modification" model of Wolbachia CI; Tram and Sullivan, 2002;Poinsot et al, 2003;Bossan et al, 2011;Shropshire et al, 2020). The models also differ in the proposed site of the CI effector-host target interaction (Figure 7) (Poinsot et al, 2003;Chen et al, 2020;Shropshire et al, 2020).…”

“…The two models differ in whether the mature sperm cells harbor a Cardinium-derived CI effector (a stockpiling method, or the "toxin-antidote" or "lock-and-key" model in the language of the Wolbachia CI literature; Hurst, 1991;Poinsot et al, 2003;Beckmann et al, 2019a;Chen et al, 2020) or not (a direct alteration method or the "host modification" model of Wolbachia CI; Tram and Sullivan, 2002;Poinsot et al, 2003;Bossan et al, 2011;Shropshire et al, 2020). The models also differ in the proposed site of the CI effector-host target interaction (Figure 7) (Poinsot et al, 2003;Chen et al, 2020;Shropshire et al, 2020). In the case of direct alteration, Cardinium produces an effector that works directly on the host target(s) throughout sperm development, beginning in the early stages of development when sperm cells are replicating and still interconnected, and proceeding through sperm maturation (Figure 7A) (Ferree et al, 2019).…”

“…The effector is then packaged within the mature sperm cell, perhaps by localizing within the nucleus during the elongation process. Upon entry of the sperm to the egg cytoplasm and prior to the start of mitosis, the CI effector then interacts with its host target (Hurst, 1991;Poinsot et al, 2003;Chen et al, 2020). Possible targets could include proteins involved in remodeling the elongated sperm nucleus via the reincorporation of maternal histones for chromatin wrapping (Loppin et al, 2005;Landmann et al, 2009;Zheng et al, 2011;Beckmann et al, 2019b).…”

“…The offspring of this cross do not harbor the symbiont, and die early in development. Offspring survive if the female is also infected with the same symbiont strain (O'Neill et al, 1997;Serbus et al, 2008;Werren et al, 2008;LePage and Bordenstein, 2013;Taylor et al, 2018;Chen et al, 2020;Shropshire et al, 2020). CI acts to drive the symbiont infection through a host population by granting infected females a fitness advantage relative to uninfected females (Turelli, 1994).…”

“…Along with other important changes, the sperm cell elongates during spermiogenesis and most of the cytoplasmic content, including any resident Wolbachia, is lost (Fuller, 1993;Clark et al, 2002Clark et al, , 2003Clark et al, , 2008Ferree et al, 2019). As Wolbachia is lost during this process and absent from mature sperm, the modification factor is hypothesized to be either deposited into sperm cells prior to Wolbachia removal (Clark et al, 2003;Chen et al, 2020) or to act upon sperm chromatin prior to sperm maturation and fertilization (Poinsot et al, 2003;Shropshire et al, 2020).…”