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Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

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Nội dung chi tiết: Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus e author.lunder. All rights reserved. No reuse allcw< nups://Knoinuvien.comTwo Liberibacter Effectors Combine to Suppress Critical Innate Immune Defen

ses andFacilitate Huanglongbing Pathogenesis in CitrusSupratim Basil5. Loan Huynh5. Shujian Zhang5, Roel Rabara5, Hau Nguyen5. Jeanette Valesquez5.Gui Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

xia Hao’. Godfrey Miles’. Qingchun Shi85. Ed Stover, and Goutam Gupta5’5Biolab. New Mexico Consortium, 100 Entrada Drive. Los Alamos, NM 87544. USA=u.

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

s. Horticultural Research Laboratory 2001 South Rock Road Fort Pierce. FL 34945. USA♦Correspondence: ggupta@newmexicoconsonium.orgbioRxỉv preprint do

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus rights reserved. No reuse allow nnps://Knotnuvien.comAbstractGenome sequence analyses predicted the presence of effectors in the gram-negative Candida

tus Liberibacter asiaticus (CLas) even without the presence of a classical type III secretion system. Since CLas is not culturable, it is not possible Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

to perform traditional gene knockout experiments to determine the role of various effectors in Huanglongbing (HLB) pathogenesis. Therefore, we follow

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

ed an alternative functional genomics approach to examine the role of the CLas effectors in HLB pathogenesis in general and more specifically in suppr

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus studies by LC-MS/MS were conducted to screen the putative interacting citrus protein partners of P235 and Effector 3 from the healthy and (Las-infecte

d Hamlin extracts and the most probable candidates were identified based upon their high protein scores from LC-MS/MS. Second, a transgenic tobacco sp Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

lit GFP system was designed for in planta detection of the most probable citrus interacting protein partners of P235 and Effector 3. Third, in vitro a

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

nd in planta studies were performed to show that each of two effectors interacts with and inhibits the functions of multiple citrus proteins belonging

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus ding protein (LTP). and induction of premature programmed cell death (PCD), thereby supporting CLas infection and HLB pathogenesis. Finally, an LTP mi

mic was designed to sequester and block the (Las effector and to rescue the bactericidal activity of LTP.Key words: effectors, immunity, modelling, RO Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

S, PAMPIntroductionHuanglongbing (HLB) is the most devastating citrus disease While endemic in Asia for over a century3-4, HLB was first encountered a

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

bout a 15 years ago in Florida with the emergence of Asian Citrus Psyllid (ACP) vectors carrying HLB-causing Candidates Liberibacter asiaticus (CLas).

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus HLB management tools are urgently needed for sustaining a productive and profitable citnis industry5. These tools include development of both bacteric

idal and anti-infective molecules for HLB treatment. Recently, we reported the development of novel citrus-derived CLas-kiUer peptides that can be use Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

d for HLB treatment bybioRxỉv preprint doi https/rơci ọra'10.1101'2021 11 26 470170; this version posted November 27.2021 Tl(which was not certified b

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

y peer review) IS the autncr/tunder. All rights reserved. No reuse altowi nups://Knoinuvien.comtopical delivery'6. Ill this study, we focused first on

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus therapeutic and anti-infective molecules to block them. Typically, the plant innate immune defense involves multiple pathways including pathogen or m

icrobe-associated molecular pattern (PAMP or MAMP) triggered immunity (PTI or MTI), effector triggered immunity (ETI). and plant hormone, such as sali Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

cylic (SA), jasmonic acid (JA), and ethylene (ET) induced immunity7*12. The PTI or MTI provides the first line of plant defense against pathogens or m

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

icrobes through the recognition of PAMP or MAMP. such as bacterial liposaccharide (LPS). elongation factor thermal unstable (EF-Tu). flagellin. PAMP o

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus (FLS2). EF-Tu receptor (EFR). The plasma membrane PRR recognition induces intracellular mitogen-associated protein kinase (MAPK) signaling leading to

the expression of pathogen-related (PR) or defense genes13'15. However, pathogen effectors can block both intracellular and extracellular steps in th Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

e PTI pathway 16,1?. To counter pathogen induced blocking of the PTI pathway, plants have evolved the ETI pathway in which intracellular nod-like rece

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

ptors (NLR) recognize the pathogen effectors and augment the MAPK signaling and PR gene expression. The ETI pathway also induces hypersensitive respon

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus ETI pathways also couple to intracellular plant hormone SA/JA/ET pathways, which also involve ROS production and induction of PR genes. It has been d

emonstrated that the effectors from plant pathogenic bacteria can inhibit one or more steps in these pathways 1S*21. Also, the bacterial effectors are Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

known to subvert multiple steps leading to programmed cell death (PCD) in plant, which is a form of immune defense by PTI and/or ETI to control infec

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

tion 22*24. Therefore, it was of interest for US to determine which steps in the citrus innate immune defense are affected by the CLas effectors. Note

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus type III or VI secretion system like many other plant pathogenic gram-negative bacteria •7’28. Gram-negative bacteria with 5 Mb genomes have several h

undred unique effectors 29 as opposed to only 20 effectors identified, so far. from CLas3013However, interactome studies revealed that even an effecto Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

r from a gram-negative bacterium carrying hundreds of effectors can target more than one protein from the host plant r-32. Therefore, it was of intere

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

st to examinebioRxN preprint doi https .''del <ỵg.'10.1101’2021 11 26 470170; this version posted November 27, 2021 Tlrn,u^.4.u.(which was not certifi

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus s proteins to effectively suppress the innate immune defense and establish infection.In this study, we focused on two CLas effectors. P235 and Effecto

r 3. First, we performed in vitro and in planta studies to identify the prominent citrus proteins targeted by P235 and Effector 3. Second, we performe Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

d functional assays to determine whether P235 and Effector 3 have inhibitory effects on their citrus protein targets. Next, we performed molecular dyn

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

amic simulations to analyze the details of interaction between P235 (and Effector 3) and their selected citrus targets and predicted which pairwise in

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus ic mutations on the citrus protein(s) that affect the critical pairwise interactions. We discovered that each of the two effectors can directly target

several citrus proteins, which belong to the innate immune networks. A clear understanding of the inhibitory mechanisms will provide guidelines for c Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

ountering CLas effectors and developing anti-infectives to block HLB pathogenesis.MethodsExperimental ProceduresPlant Materials and growth conditions.

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

Hamlin trees verified as being HLB-free and ACP-friendly were purchased and placed in the green house. One branch cage placed in the upper part of ea

bioRxiv preprint doi https .•■dci pra-10 1101-2021 11 26470170; this version posted November 27. 2021 Tl{which was not certihea by peer review) ts the

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus insects were allowed to feed on the trees for a week and then the insects were killed by spraying with topical insecticide. The ACPs were tested for C

.Las and the trees were subsequently returned to the greenhouse. Leaf samples were collected from the untreated and infected plants and flash frozen i Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

n liquid nitrogen and stored for further analysis.Cloning and overexpression of effectors and targets in E. coli. The effectors from Liberibacter asia

Two liberibacter effectors combine to suppress critical innate immune defenses and facilitate huanglongbing pathogenesis in citrus

ticus were identified, codon optimized and cloned in pUC57 by GenScript. The effectors were then amplified and cloned in pET28(a) vector between Ndel

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