The peritrophic matrix (PM) is an acellular membrane that covers the gut epithelium in arthropods and physically separates it from the lumen. The structure is thought to play an important role in tick biology. The PM is also known to impact the persistence of tick‐borne pathogens like Borrelia burgdorferi, although limited information is available about its molecular constituents or their biological significance. Herein, we characterise a novel PM‐associated gut protein in Ixodes scapularis ticks, annotated as Peritrophic Membrane Chitin Binding Protein (PM_CBP), for its role in the integrity and function of the matrix. The PM_CBP displays homology to the chitin deacetylase metalloenzyme, shows upregulation during tick feeding, and is localized at the luminal surface of the gut epithelium. The structural integrity of the PM was impaired both by the knock down of PM_CBP expression via RNA interference and by treatment with anti‐PM_CBP antibodies, as revealed by its electron microscopic appearance. Additionally, the duration of tick engorgement on mice and the passage of experimentally‐inoculated fluorescent dextran molecules across the PM are affected by the knock down of PM_CBP expression. The transfer of anti‐PM_CBP antibodies into the tick gut impacted the overall composition of the resident microbiome, and also influenced B. burgdorferi acquisition in ticks and its transmission to mice. Taken together, these data highlight the biological significance of the Ixodes PM and suggest that the targeting of its molecular constituents may contribute to the development of novel interventions against tick‐borne infections.
Retroelement transcripts are present in male and female gametes, where they are typically regulated by methylation, noncoding RNAs and transcription factors. Such transcripts are required for occurrence of retrotransposition events, while failure of retrotransposition control may exert negative effects on cellular function and proliferation. In order to investigate the occurrence of retrotransposition events in mouse epididymal spermatozoa and to address the impact of uncontrolled retroelement RNA expression in early preimplantation embryos, we performed in vitro fertilization experiments using spermatozoa preincubated with plasmid vectors containing the human retroelements LINE-1, HERVK-10 or the mouse retroelement VL30, tagged with an enhanced green fluorescence (EGFP) gene-based cassette. Retrotransposition events in mouse spermatozoa and embryos were detected using PCR, FACS analysis and confocal microscopy. Our findings show that: (i) sperm cell incorporates exogenous retroelements and favors retrotransposition events, (ii) the inhibition of spermatozoa reverse transcriptase can decrease the retrotransposition frequency in sperm cells, (iii) spermatozoa can transfer exogenous human or mouse retroelements to the oocyte during fertilization and (iv) retroelement RNA overexpression affects embryo morphology and impairs preimplantation development. These findings suggest that the integration of exogenous retroelements in the sperm genome, as well as their transfer into the mouse oocyte, could give rise to new retrotransposition events and genetic alterations in mouse spermatozoa and embryos.Reproduction (2016) 152 [185][186][187][188][189][190][191][192][193]
Our results show that: 1) LINE-1, HERV-K10, and SVA retrotransposons are transcriptionally expressed in human spermatozoa; 2) cloned active retroelements of human and mammalian origin can be incorporated in human sperm genome; 3) active reverse transcriptases exist in human spermatozoa; and 4) de novo retrotransposition events occur in human spermatozoa.
Studying the different check points of the VEGF pathway, we conclude that targeting calcium pathways could be beneficial for the vascular permeability control in an OHSS animal model.
Borrelia burgdorferi sensu lato causes Lyme borreliosis in a variety of animals and humans. These atypical bacterial pathogens are maintained in a complex enzootic life cycle that primarily involves a vertebrate host and Ixodes spp. ticks. In the Northeastern United States, I. scapularis is the main vector, while wild rodents serve as the mammalian reservoir host. As B. burgdorferi is transmitted only by I. scapularis and closely related ticks, the spirochete-tick interactions are thought to be highly specific. Various borrelial and arthropod proteins that directly or indirectly contribute to the natural cycle of B. burgdorferi infection have been identified. Discrete molecular interactions between spirochetes and tick components also have been discovered, which often play critical roles in pathogen persistence and transmission by the arthropod vector. This review will focus on the past discoveries and future challenges that are relevant to our understanding of the molecular interactions between B. burgdorferi and Ixodes ticks. This information will not only impact scientific advancements in the research of ticktransmitted infections but will also contribute to the development of novel preventive measures that interfere with the B. burgdorferi life cycle. caister.com/cimb 113 Curr. Issues Mol. Biol. Vol. 42 Curr. Issues Mol. Biol. 42: 113-144. caister.com/cimb Interactions Between Ticks and Spirochetes Pal et al.scapularis are highly specific. Limited studies have shed light on these complex pathogen-tick interactions (Munderloh and Kurtti, 1995;Fikrig and Narasimhan, 2006); a recent review summarizes our most current state of knowledge about the interactions between B. burgdorferi and I. scapularis ticks (Kurokawa et al., 2020). Vector competence, which depends on genetic determinants influencing the vector's ability to transmit a pathogen, also shapes interactions involving the tick, pathogen, and host (de la Fuente et al., 2017). With the advent of genetic tools for creating Borrelia mutants (Samuels et al., 2018) (see also Radolf and Samuels, 2021) and the current availability of the I. scapularis genome (Gulia-Nuss et al., 2016;Miller et al., 2018), investigators will have increasingly robust tools for studying Borrelia-tick interactions, both during the arthropod phase of the spirochete life cycle and at the interface with the mammalian host. A few borrelial proteins already have been demonstrated as prerequisites for spirochete-vector interactions, particularly with receptors in select tick organs, such as the gut or salivary gland (
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