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1. Phylogenomic Diversity Elucidates Mechanistic Insights into Lyme Borreliae-Host Association

   https://doi.org/10.1128/msystems.00488-22  

   Combs, Matthew ; Marcinkiewicz, Ashley L. ; Dupuis, Alan P. ; Davis, April D. ; Lederman, Patricia ; Nowak, Tristan A. ; Stout, Jessica L. ; Strle, Klemen ; Fingerle, Volker ; Margos, Gabriele ; et al ( August 2022 , mSystems)

   Gilbert, Jack A. (Ed.)

   ABSTRACT Host association—the selective adaptation of pathogens to specific host species—evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi sensu lato complex, including B. burgdorferi ( Bb ), the main LD pathogen in North America—a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens’ ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host-adapted phenotypes among Bb strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 Bb strains in sera in vitro and/or bloodstream and tissues in vivo from rodent and avian LD models. Three groups of complement-dependent host-association phenotypes emerged. We analyzed complement-evasion genes, identified a priori among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of ospC loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests that several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host-adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. IMPORTANCE Host association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD)-causing agent, B. burgdorferi ( Bb ), is an ideal model to study host association, as Bb is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in Bb strains is linked to Bb functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 Bb strains into three complement-dependent host-association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including ospC , with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction. 

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2. The PTI ‐suppressing Avr2 effector from Fusarium oxysporum suppresses mono‐ubiquitination and plasma membrane dissociation of BIK1

   https://doi.org/10.1111/mpp.13369  

   Blekemolen, Mila C. ; Liu, Zunyong ; Stegman, Martin ; Zipfel, Cyril ; Shan, Libo ; Takken, Frank L. W. ( June 2023 , Molecular Plant Pathology)

   Plant pathogens use effector proteins to target host processes involved in pathogen perception, immune signalling, or defence outputs. Unlike foliar pathogens, it is poorly understood how root‐invading pathogens suppress immunity. The Avr2 effector from the tomato root‐ and xylem‐colonizing pathogenFusarium oxysporumsuppresses immune signalling induced by various pathogen‐associated molecular patterns (PAMPs). It is unknown how Avr2 targets the immune system. TransgenicAVR2 Arabidopsis thalianaphenocopies mutants in which the pattern recognition receptor (PRR) co‐receptor BRI1‐ASSOCIATED RECEPTOR KINASE (BAK1) or its downstream signalling kinase BOTRYTIS‐INDUCED KINASE 1 (BIK1) are knocked out. We therefore tested whether these kinases are Avr2 targets. Flg22‐induced complex formation of the PRR FLAGELLIN SENSITIVE 2 and BAK1 occurred in the presence and absence of Avr2, indicating that Avr2 does not affect BAK1 function or PRR complex formation. Bimolecular fluorescence complementation assays showed that Avr2 and BIK1 co‐localize in planta. Although Avr2 did not affect flg22‐induced BIK1 phosphorylation, mono‐ubiquitination was compromised. Furthermore, Avr2 affected BIK1 abundance and shifted its localization from nucleocytoplasmic to the cell periphery/plasma membrane. Together, these data imply that Avr2 may retain BIK1 at the plasma membrane, thereby suppressing its ability to activate immune signalling. Because mono‐ubiquitination of BIK1 is required for its internalization, interference with this process by Avr2 could provide a mechanistic explanation for the compromised BIK1 mobility upon flg22 treatment. The identification of BIK1 as an effector target of a root‐invading vascular pathogen identifies this kinase as a conserved signalling component for both root and shoot immunity.

    

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3. Never Walk Alone: Clathrin-Coated Vesicle (CCV) Components in Plant Immunity

   https://doi.org/10.1146/annurev-phyto-080417-045841  

   Ekanayake, Gayani ; LaMontagne, Erica D. ; Heese, Antje ( August 2019 , Annual Review of Phytopathology)

   null (Ed.)

   At the host–pathogen interface, the protein composition of the plasma membrane (PM) has important implications for how a plant cell perceives and responds to invading microbial pathogens. A plant's ability to modulate its PM composition is critical for regulating the strength, duration, and integration of immune responses. One mechanism by which plant cells reprogram their cell surface is vesicular trafficking, including secretion and endocytosis. These trafficking processes add or remove cargo proteins (such as pattern-recognition receptors, transporters, and other proteins with immune functions) to or from the PM via small, membrane-bound vesicles. Clathrin-coated vesicles (CCVs) that form at the PM and trans-Golgi network/early endosomes have emerged as the prominent vesicle type in the regulation of plant immune responses. In this review, we discuss the roles of the CCV core, adaptors, and accessory components in plant defense signaling and immunity against various microbial pathogens. 

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4. Protection of host cells by complement regulators

   https://doi.org/10.1111/imr.12475  

   Schmidt, Christoph Q. ; Lambris, John D. ; Ricklin, Daniel ( October 2016 , Immunological Reviews)

   The complement cascade is an ancient immune‐surveillance system that not only provides protection from pathogen invasion but has also evolved to participate in physiological processes to maintain tissue homeostasis. The alternative pathway (AP) of complement activation is the evolutionarily oldest part of this innate immune cascade. It is unique in that it is continuously activated at a low level and arbitrarily probes foreign, modified‐self, and also unaltered self‐structures. This indiscriminate activation necessitates the presence of preformed regulators on autologous surfaces to spare self‐cells from the undirected nature ofAPactivation. Although the other two canonical complement activation routes, the classical and lectin pathways, initiate the cascade more specifically through pattern recognition, their activity still needs to be tightly controlled to avoid excessive reactivity. It is the perpetual duty of complement regulators to protect the self from damage inflicted by inadequate complement activation. Here, we review the role of complement regulators as preformed mediators of defense, explain their common and specialized functions, and discuss selected cases in which alterations in complement regulators lead to disease. Finally, rational engineering approaches using natural complement inhibitors as potential therapeutics are highlighted.

    

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5. Ecoimmunological differences among congeneric tortoises in the United States

   https://doi.org/10.1111/jzo.13109  

   Sandmeier, F. C. ; Morales, J. ; Gomez, M. ; Kester, M. ; Gann‐Archuleta, K. ; Crooker, C. ; Goessling, J. M. ; Tracy, C. R. ; Weitzman, C. L. ( August 2023 , Journal of Zoology)

   Comparative studies, especially of related species that span across ecoregions, have the potential to increase our understanding of different ecological or evolutionary pressures that may drive host–pathogen dynamics. We quantified differences in immune investment, via differential leukocyte counts and bacteria‐killing assays, across four closely related species ofGopherustortoises, found across a gradient from the desert southwest to the subtropical southeast of the United States. We further quantified differences in a commensal nasal microbe (Pasteurella testudinis) and tested for associations among immune measures,P. testudinis, and previously quantified levels of the pathogenMycoplasma agassiziiand upper respiratory tract disease (URTD). We also evaluated the potential influence of environmental variables on immune investment,P. testudinis, and disease. We found that tortoise species in more arid environments had a reduced investment in inflammatory leukocytes, possibly as a strategy to reduce water loss, and invested more heavily in innate anti‐inflammatory leukocytes. Conversely, we found that species in moister, resource‐rich environments may face greater pathogen pressure, likely due to increased population densities and transmission rates among host tortoises. These tortoises had increased investment in inflammatory cells and appeared to reduce their nasal microbes (includingP. testudinis) when they exhibited URTD. Thus, we quantified two negative correlational patterns: (1) between inflammatory responses and water conservation and (2) between resource quality and transmission rates. We hypothesize that these relationships across species may reflect variable development or evolution of innate immune functions.

    

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