Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution

Song, Dingka; Meng, Junchen; Cheng, Jie; Fan, Zheng; Chen, Pengyu; Ruan, Hefei; Tu, Zhongyuan; Kang, Ning; Li, Nan; Xu, Ying; Wang, Xiaobo; Shu, Fei; Mu, Libing; Li, Tengfei; Ren, Wenran; Lin, Xin; Zhu, Jun; Fang, Xiaohong; Amrein, Matthias; Wu, Weihui; Yan, Li‐Tang; Lü, Junhong; Xia, Tie; Shi, Yan

doi:10.1038/s41564-018-0290-8

Cited by 80 publications

(77 citation statements)

References 74 publications

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“…Hosts and symbionts constantly exchange small metabolites during interkingdom interactions. For example, the plant pathogenic bacterium Pseudomonas syringae produces the phytotoxin coronatine to target multiple plant immunity pathways, including stomatal defence, thus facilitate bacterial entry as well as disease development (61–64). Conversely, the transfer of small molecules from plants to microbes is also an integral part of microbial symbiotic relationships (65, 66).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous reports highlighted the effects of QS molecules on plant development and immunity, but mechanistic insights on how bacterial QS molecules specifically interfere with host biology remain sparse (70). Distinctive acylation and hydroxylation patterns in bacterial metabolites have been suggested as a molecular signature of AHL QS family to regulate host immune responses (71, 72). For example, medium-chained 3-hydroxy fatty acids directly bind and trigger the phosphorylation of LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) receptor kinase, leading to activation of cytoplasmic receptor-like kinases and stimulate FRK1 expression (71, 73).…”

Section: Discussionmentioning

confidence: 99%

“…It will also be of particular interest to investigate if the regulation of host metabolic pathways by different small molecules from pathogens is a ubiquitous phenomenon during host-pathogen interaction. In addition, since quorum-sensing molecules from human pathogens, such as P. aeruginosa have also been documented to disrupt host membrane microdomains (72), it is worth future studies to investigate whether signalling of plasma membrane receptors such as TLR5 (an ortholog of FLS2) is also affected by such molecule in a sterol-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

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The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

Tran

Triebl

et al. 2020

Preprint

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36Quorum sensing (QS) is a recognized phenomenon that is crucial for regulating population-37 related behaviors in bacteria. However, the direct specific effect of QS molecules on host biology is 38 largely under-studied. In this work, we show that the QS molecule DSF (cis-11-methyl-dodecenoic acid) 39 produced by Xanthomonas campestris pv. campestris can suppress pathogen-associated molecular 40 pattern (PAMP)-triggered immunity (PTI) in Arabidopsis thaliana, mediated by flagellin-induced activation 41 of flagellin receptor FLS2. The DSF-mediated attenuation of innate immunity results from the alteration of 42 oligomerization states and endocytic internalization of plasma membrane FLS2. DSF altered the lipid 43 profile of Arabidopsis, with a particular increase of the phytosterol species, which impairs the general 44 endocytosis pathway mediated by clathrin and FLS2 nano-clustering on the plasma membrane. The DSF 45 effect on receptor dynamics and host immune responses could be entirely reversed by sterol removal. 46Together, our results highlighted the importance of sterol homeostasis to plasma membrane organization 47 and demonstrate a novel mechanism by which pathogenic bacteria use their communicating molecule to 48 manipulate PAMP-triggered host immunity. 49 50 Keywords: quorum sensing, plasma membrane, endocytosis, plant-pathogen interaction 51 52 SIGNIFICANCE STATEMENT 53Bacteria rely on small signalling molecules called quorum sensing (QS) signals to communicate 54 and coordinate their behaviors. QS is known to regulate gene expression, production of virulence factors, 55 and biofilm formation for pathogenic bacteria to effectively colonize their hosts and cause diseases. In this 56 work, we found a class of QS molecule called diffusible-signal factor (DSF), produced by devastating 57 phytopathogenic bacteria such as Xanthomonas spp. and Xylella fastidiosa, could communicate directly 58 with plant host and subvert plant innate immunity by inducing plant sterol production and thereby, 59 attenuating receptor signalling through hindering the receptor clustering and plant endocytosis. The 60 results significantly enrich our understanding of the mechanisms in the tug-of-war between bacterial 61 pathogenesis and host immunity. 62 63 infection (4). The 3OC12-HSL was also shown to be recognized by the bitter taste receptor, T2R family 73 protein, T2R38 in neutrophils, lymphocytes and monocytes to activate innate immune responses (5). 74Similarly, plant pathogenic bacteria also secrete small-molecule virulence factors to cross-talk with host 75 and manipulate host immunity during infection. QS molecules produced by several bacterial 76 phytopathogens showed a wide range of interference in host development and defence mechanisms, 77including the root morphological development in an auxin-dependent manner or callose deposition during 78 immune responses (6-8). However, the detailed mechanisms of how QS molecules directly influence 79 plant host development and pathology, especially the PAMP-mediated host immunity,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

Tran

Triebl

et al. 2020

Preprint

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“…Also, P. aeruginosa could induce apoptosis by producing pyocyanin, a pigment generating reactive oxygen intermediates and reducing intracellular cyclic adenosine monophosphate in host cells (Usher et al, ). In addition, 3‐oxo‐C12‐HSL, the lasR ‐type QS signal of P. aeruginosa , could also induce apoptosis by abrogating the calcium signalling and the Janus kinase/signal transducer and activator of transcription pathway in host cells (Li, Hooi, Chhabra, Pritchard, & Shaw, ; Schwarzer et al, ; Song et al, ). Our findings that IQS, as an additional class of QS signal different from N ‐acylhomoserine lactone, induced host cell apoptosis through POT1–p53 signalling pathway, provide a new layer of evidence on the complexity of bacterial infectivity and pathogen–host interaction.…”

Section: Discussionmentioning

confidence: 99%

Bacterial quorum‐sensing signal IQS induces host cell apoptosis by targeting POT1–p53 signalling pathway

Wang

et al. 2019

Cellular Microbiology

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Pseudomonas aeruginosa, an opportunistic life-threatening human bacterial pathogen, employs quorum-sensing (QS) signal molecules to modulate virulence gene expression. 2-(2-hydroxyphenyl)-thiazole-4-carbaldehyde (IQS) is a recently identified QS signal that integrates the canonical lasR-type QS of P. aeruginosa and host phosphate stress response to fine-tune its virulence production for a successful infection. To address the role of IQS in pathogen-host interaction, we here present that IQS inhibits host cell growth and stimulates apoptosis in a dosage-dependent manner. By downregulating the telomere-protecting protein POT1 in host cells, IQS activates CHK1, CHK2, and p53 in an Ataxia telangiectasia mutated (ATM)/ATM and RAD3-related (ATR)-dependent manner and induces DNA damage response.Overexpression of POT1 in host cells presents a resistance to IQS treatment. These results suggest a pivotal role of IQS in host apoptosis, highlighting the complexity of pathogenesis mechanisms developed by P. aeruginosa during infection.

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“…A novel study presents the bacterial qourum-sensing autoinducer of the Pseudomonas aeruginosa N-(3-oxo-dodecanoyl) homoserine lactone (3oc), a small chemical released to control microbial communication, as an inducer of TNFR1. It is demonstrated that 3oc directly disrupts the lipid domain structures, containing sphingolipids and cholesterol, and induces the translocation of TNFR1 into the disordered lipid phase of the membrane, which in turn triggers the trimerization of the TNFR and leads to subsequent apoptosis in human and mice monocytes (Song et al, 2019). This type of TNFR activation ensures a ligand independent induction of the extrinsic pathway.…”

Section: Canonical Caspase-8 Activation In Response To Bacterial Infementioning

confidence: 99%

The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis

Imre

2020

International Review of Cell and Molecular Biology

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Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution

Cited by 80 publications

References 74 publications

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

Bacterial quorum‐sensing signal IQS induces host cell apoptosis by targeting POT1–p53 signalling pathway

The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis

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