Legionella pneumophila infection is enhanced in a RacH-null mutant of Dictyostelium

Balest, Alessandra; Peracino, Barbara; Bozzaro, Salvatore

doi:10.4161/cib.4.2.14381

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Only a handful of bacteria strains are not phagocytosed, but very few systematic studies have been published in this regard. Legionella pneumophila is taken up by macropinocytosis, thus its uptake by natural wild type strains is negligible (Peracino et al, 2010; Balest et al, 2011). Bacillus anthracis was reported not to be phagocytosed (Depraitere and Darmon, 1978), but a recent report described its uptake, though no details were offered on the efficiency of phagocytosis (Nasser et al, 2013).…”

Section: Dictyostelium: Professional Phagocyte and Pathogen Hostmentioning

confidence: 99%

Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

Bozzaro¹,

Buracco²,

Peracino³

2013

Front. Cell. Infect. Microbiol.

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Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other “iron genes” will help identify genes essential for iron homeostasis and resistance to pathogens.

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Section: Dictyostelium: Professional Phagocyte and Pathogen Hostmentioning

confidence: 99%

Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

Bozzaro¹,

Buracco²,

Peracino³

2013

Front. Cell. Infect. Microbiol.

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“…To test this hypothesis, we used a RacH‐ Dictyostelium strain whose vesicle trafficking is disrupted due to defective acidification of early endosomes. This impairs macropinocytosis and chemotaxis (Somesh et al , 2006; Balest et al , 2011) As shown in Fig 4G, whereas a back‐to‐front gradient in PI(3,4)P2 membrane association was apparent in wild‐type Dictyostelium AX2 cells, in the RacH‐ cells “back” regions were weaker and there were more cytosolic PI(3,4)P2‐enriched vesicles. Line scans of pixel intensity across wild‐type or mutant cells confirmed greater PI(3,4)P2 accumulation at the back of wild‐type cells (Fig 4H).…”

Section: Resultsmentioning

confidence: 95%

“…Somesh et al, 2006;Balest et al, 2011) As shown in Fig 4G, whereas a back-to-front gradient in PI(3,4)P2 membrane association was apparent in wild-type Dictyostelium AX2 cells, in the RacHcells "back" regions were weaker and there were more cytosolic PI(3,4)P2-enriched vesicles. Line scans of pixel intensity across wild-type or mutant cells confirmed greater PI(3,4)P2 accumulation at the back of wild-type cells (Fig 4H).…”

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confidence: 70%

Reverse fountain flow of phosphatidylinositol‐3,4‐bisphosphate polarizes migrating cells

Pal

Biswas

et al. 2021

The EMBO Journal

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The ability of cells to polarize and move toward external stimuli plays a crucial role in development, as well as in normal and pathological physiology. Migrating cells maintain dynamic complementary distributions of Ras activity and of the phospholipid phosphatidylinositol‐3,4‐bisphosphate (PI(3,4)P2). Here, we show that lagging‐edge component PI(3,4)P2 also localizes to retracting leading‐edge protrusions and nascent macropinosomes, even in the absence of phosphatidylinositol 3,4,5‐trisphosphate (PIP3). Once internalized, macropinosomes break up into smaller PI(3,4)P2‐enriched vesicles, which fuse with the plasma membrane at the rear of the cell. Subsequently, the phosphoinositide diffuses toward the front of the cell, where it is degraded. Computational modeling confirms that this cycle gives rise to stable back‐to‐front gradient. These results uncover a surprising “reverse‐fountain flow” of PI(3,4)P2 that regulates polarity.

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“…Therefore, it has been proposed that RacH acts as a regulator of vesicle sorting. Furthermore, RacH also plays an important role in host–pathogen interactions, as it was shown that racH -null cells are more susceptible to infection by Mycobacterium marinum or Legionella pneumophila : the bacteria proliferate more easily in racH -null cells, which was attributed to a defect in endosome acidification [ 302 , 303 ]. On the other hand, the depletion of RacH has a deteriorating impact on bacterial transmission between Dictyostelium cells, since the release of bacteria from racH -null cells is almost completely abrogated [ 303 ].…”

Section: Comparative Analysis Of the Rho Signalling In Dictyostelium And Mammalian Cellsmentioning

confidence: 99%

Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

Filić

Mijanović

Putar

et al. 2021

Cells

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Both Dictyostelium amoebae and mammalian cells are endowed with an elaborate actin cytoskeleton that enables them to perform a multitude of tasks essential for survival. Although these organisms diverged more than a billion years ago, their cells share the capability of chemotactic migration, large-scale endocytosis, binary division effected by actomyosin contraction, and various types of adhesions to other cells and to the extracellular environment. The composition and dynamics of the transient actin-based structures that are engaged in these processes are also astonishingly similar in these evolutionary distant organisms. The question arises whether this remarkable resemblance in the cellular motility hardware is accompanied by a similar correspondence in matching software, the signalling networks that govern the assembly of the actin cytoskeleton. Small GTPases from the Rho family play pivotal roles in the control of the actin cytoskeleton dynamics. Indicatively, Dictyostelium matches mammals in the number of these proteins. We give an overview of the Rho signalling pathways that regulate the actin dynamics in Dictyostelium and compare them with similar signalling networks in mammals. We also provide a phylogeny of Rho GTPases in Amoebozoa, which shows a variability of the Rho inventories across different clades found also in Metazoa.

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Legionella pneumophila infection is enhanced in a RacH-null mutant of Dictyostelium

Cited by 6 publications

References 23 publications

Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

Reverse fountain flow of phosphatidylinositol‐3,4‐bisphosphate polarizes migrating cells

Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

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