Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables
            <i>Pseudomonas</i>
            to evade opsonization

Haller, Samantha; Franchet, Adrien; Hakkim, Abdul; Chen, Jing; Drenkard, Eliana; Song, Yu; Schirmeier, Stefanie; Li, Zi; Martins, Nelson; Ausubel, Frederick M.; Liégeois, Samuel; Ferrandon, Dominique

doi:10.15252/embr.201744880

Cited by 26 publications

(35 citation statements)

References 84 publications

(125 reference statements)

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“…These secreted molecules bind to the pathogens and promote their phagocytosis by the macrophages. Tep1 and Tep4 (Dostalova et al , ; Haller et al , ) are among the genes expressed at the highest levels in WL hemocytes, and Tep1 presents the strongest enrichment. Most of the genes involved in phagosome formation are also enriched at this stage: Arp3, Rac1, Rac2, SCAR, WASP, Chic, and Cdc42 (Pearson et al , ).…”

Section: Resultsmentioning

confidence: 99%

Temporal specificity and heterogeneity of Drosophila immune cells

et al. 2020

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Immune cells provide defense against non‐self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity of Drosophila immune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single‐cell RNA sequencing, we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct processes, e.g., proliferation, phagocytosis, metabolic homeostasis, and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation, which triggers the differentiation of a novel hemocyte type, the lamellocyte. This first molecular atlas of hemocytes provides insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.

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Section: Resultsmentioning

confidence: 99%

Temporal specificity and heterogeneity of Drosophila immune cells

et al. 2020

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“…The consequences of this intraspecies interaction may explain the worse outcomes exhibited by patients in which LasR− strains are detected ( 13 ), but future studies that include genotypes, monoculture and coculture phenotypes, and longitudinal outcome data will be required. RhlR plays other important roles in host interactions ( 75 ) which may benefit P. aeruginosa LasR− strains. The observation that rhlR mutants are rare in natural isolates and that LasR− strains with active RhlR are virulent ( 25 , 76 ) underscores the relevance of this mechanism and highlights the importance of understanding how microbial interactions influence RhlR activity.…”

Section: Discussionmentioning

confidence: 99%

Intraspecies Signaling between Common Variants of Pseudomonas aeruginosa Increases Production of Quorum-Sensing-Controlled Virulence Factors

Mould

Botelho

Hogan

2020

mBio

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The opportunistic pathogen Pseudomonas aeruginosa damages hosts through the production of diverse secreted products, many of which are regulated by quorum sensing (QS). The lasR gene, which encodes a central QS regulator, is frequently mutated in clinical isolates from chronic infections, and loss of LasR function (LasR−) generally impairs the activity of downstream QS regulators RhlR and PqsR. We found that in cocultures containing LasR+ and LasR− strains, LasR− strains hyperproduce the RhlR/RhlI-regulated antagonistic factors pyocyanin and rhamnolipids in diverse models and media and in different strain backgrounds. Diffusible QS autoinducers produced by the wild type were not required for this effect. Using transcriptomics, genetics, and biochemical approaches, we uncovered a reciprocal interaction between wild-type and lasR mutant pairs wherein the iron-scavenging siderophore pyochelin produced by the lasR mutant induced citrate release and cross-feeding from the wild type. Citrate, a metabolite often secreted in low iron environments, stimulated RhlR signaling and RhlI levels in LasR−but not in LasR+ strains. These studies reveal the potential for complex interactions between recently diverged, genetically distinct isolates within populations from single chronic infections. IMPORTANCE Coculture interactions between lasR loss-of-function and LasR+ Pseudomonas aeruginosa strains may explain the worse outcomes associated with the presence of LasR− strains. More broadly, this report illustrates how interactions within a genotypically diverse population, similar to those that frequently develop in natural settings, can promote unpredictably high virulence factor production.

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“…Next, we challenged the BaraA mutant lines with the Gram-positive bacterium Staphylococcus albus and did not observe any enhanced sensitivity to this infection ( robertsii infection, we also tested PAO1 in an intestinal infection model in which bacteria escape the gut compartment and ultimately cause a generalized bacteremia (Haller et al, 2018;Limmer et al, 2011). BaraA isogenized KO and KI mutant lines also did not display any increased susceptibility when compared to the control line (Fig.…”

Section: Generation Of Mutants Affecting the Expression Of The Baraa mentioning

confidence: 99%

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

Hunag

Lou

Liu

et al. 2020

Preprint

Self Cite

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The host defense against several Gram-positive bacterial and fungal infections is mostly mediated by the Toll pathway in Drosophila, which regulates the expression of multiple genes including effectors of the innate immune response. One such potential effector is IMPPP/BaraA, a precursor protein that is processed at furin cleavage sites into an armamentarium of small DIM peptides that display a high degree of sequence similarity. We report here the generation of multiple mutants affecting this gene. Our phenotypic analysis revealed a specific sensitivity to pathogens belonging to distinct kingdoms, the Gram-positive bacterium Enterococcus faecalis and the entomopathogenic fungus Metarhizium anisopliae, only in septic injury models of infection. Unexpectedly, we failed to reveal a consistently increased microbial burden in the mutant flies infected with either of these microorganisms, opening the possibility for a role of BaraA in resilience rather than in resistance, which we were however unable to confirm. We also found that some BaraA-derived DIM peptides display an antimicrobial activity at millimolar concentrations in vitro. BaraA is additionally required for an efficient cleavage of pro-phenol oxidase into an active enzyme. BaraA is also involved in the cellular host defense, but through distinct mechanisms: it needs to be expressed in hemocytes for an efficient response solely to E. faecalis infection whereas it is required for the uptake by plasmatocytes of M. robertsii conidia. We propose a model whereby BaraA secreted by hemocytes may act at a very short range and protect host tissues or organs targeted specifically by E. faecalis. This study thus reveals an unexpected functional complexity of a potential effector of the Toll pathway in the host defense against specific infections.

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Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization

Cited by 26 publications

References 84 publications

Temporal specificity and heterogeneity of Drosophila immune cells

Temporal specificity and heterogeneity of Drosophila immune cells

Intraspecies Signaling between Common Variants of Pseudomonas aeruginosa Increases Production of Quorum-Sensing-Controlled Virulence Factors

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

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