dictyNews

Electronic Edition

Volume 46, number 31

December 11, 2020



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Abstracts

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Zn2+ intoxication of Mycobacterium marinum during Dictyostelium 

discoideum infection is counteracted by induction of the pathogen 

Zn2+ exporter CtpC



Nabil Hanna1, Hendrik Koliwer-Brandl3, Louise H. Lefrançois1, 

Vera Kalinina1,2, Elena Cardenal-Muñoz1, Joddy Appiah1, Florence 

Leuba1, Aurélie Gueho1,4, Hubert Hilbi3, Thierry Soldati1¥* and 

Caroline Barisch1,5¥*



¥ These authors contributed equally

*Corresponding authors



1Department of Biochemistry, Faculty of Science, University of Geneva, 

Geneva, Switzerland

2Present address: Institute of Cytology, Russian Academy of Sciences, 

St. Petersburg, Russia

3Institute of Medical Microbiology, University of Zurich, Zurich, 

Switzerland

4Present address: Protim, Université de Rennes, Rennes, France

5Present address: Division of Molecular Infection Biology, Department 

of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany





mBio, in press



Macrophages use diverse strategies to restrict intracellular pathogens, 

including either depriving the bacteria of (micro)nutrients such as 

transition metals, or intoxicating them via metal accumulation. Little is 

known about the chemical warfare between Mycobacterium marinum, 

a close relative of M. tuberculosis (Mtb), and its hosts. We use the 

professional phagocyte Dictyostelium discoideum to investigate the 

role of Zn2+ during M. marinum infection. We show that M. marinum 

senses toxic levels of Zn2+ and responds by upregulating one of its 

isoforms of the Zn2+ efflux transporter CtpC. Deletion of ctpC 

(MMar_1271) leads to growth inhibition in broth supplemented with 

Zn2+ as well as reduced intracellular growth. Both phenotypes were 

fully rescued by constitutive ectopic expression of the Mtb CtpC 

orthologue demonstrating that MMar_1271 is the functional CtpC Zn2+ 

efflux transporter in M. marinum. Infection leads to the accumulation of 

Zn2+ inside the Mycobacterium-containing vacuole (MCV), achieved by 

the induction and recruitment of the D. discoideum Zn2+ efflux pumps 

ZntA and ZntB. In cells lacking ZntA, there is further attenuation of 

M. marinum growth, presumably due to a compensatory efflux of Zn2+ 

into the MCV, carried out by ZntB, the main Zn2+ transporter in 

endosomes and phagosomes. Counterintuitively, bacteria growth is also 

impaired in zntB KO cells, in which MCVs appear to accumulate less 

Zn2+ than in wild type cells, suggesting restriction by other Zn2+-

mediated mechanisms. Absence of CtpC further epistatically attenuates 

the intracellular proliferation of M. marinum in zntA and zntB KO cells, 

confirming that mycobacteria face noxious levels of Zn2+.





submitted by: Caroline Barisch [[log in to unmask]]

_________________________________________________________





From environmental sensing to developmental control – cognitive 

evolution in Dictyostelid social amoebas



Pauline Schaap



School of Life Sciences, University of Dundee, Dundee DD15EH, UK





Phil Trans Soc B in press



Dictyostelid social amoebas respond to starvation by self-organizing 

into multicellular slugs that migrate towards light to construct spore-

bearing structures. These behaviours depend on excitable networks 

that enable amoebas to produce propagating waves of the 

chemoattractant cAMP, and to respond by directional movement. 

cAMP additionally regulates cell differentiation throughout development, 

with differentiation and cell movement being coordinated by interaction 

of the stalk inducer c-di-GMP with the adenylate cyclase that generates 

cAMP oscillations. Evolutionary studies indicate how the manifold roles 

of cAMP in multicellular development evolved from a role as 

intermediate for starvation-induced encystation in the unicellular 

ancestor. A merger of this stress response with the chemotaxis 

excitable networks yielded the developmental complexity and cognitive 

capabilities of extant Dictyostelia.





submitted by: Pauline Schaap [[log in to unmask]]

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[End dictyNews, volume 46, number 31]