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Modelling the lifecycle of "Candidatus Midichloria mitochondrii" using electron microscopy data

The majority of arthropods live in strict symbiotic relationships with bacteria that provide them with nutrients or defense mechanisms, some of them even living within host cells. The intramitochondrial bacterium Midichloria mitochondrii is probably one of the most intriguing endosymbiotic bacteria ever detected: it is the only known bacterium able to colonize the mitochondria of its host. At the state of the art, little information is available about the lifecycle of this unique symbiont. Combining mathematical modelling and electron microscopy, we reconstructed the probable lifecycle of the bacterium within the host cells, which appears to include the capability to move from one mitochondrion to another.

The life and physiology of several arthropod species is strictly connected to symbiotic bacteria, microorganisms able to colonize different parts of the host's body and to deeply affect its physiology. In some cases, endosymbiotic bacteria are pivotal to the host's fitness and survival, providing nutrients, protecting it from pathogens or conferring resistance to insecticides. Some bacterial species are even able to manipulate the reproduction of the host, e.g., by inducing parthenogenesis.

 

Figure: transmission electron microscopy image of an oocyte of the tick Ixodes ricinus. Mitochondria can be seen in grey with the characteristic cristae, while Midichloria bacteria are the darker cells.

The Intramitochondrial Bacterium 

Until now, tens of endosymbiotic bacterial species have been described, often characterized by peculiar lifestyles and symbiotic strategies. Among these, Midichloria mitochondrii is one of the most intriguing: indeed, it is the first described bacteria able to colonize its host’s mitochondria, the organelles known for energy production but fundamental for many other cell functions. 

Understanding the mechanisms at the basis of this interaction could provide novel clues on the functioning of mitochondria.

Furthermore, the host of M. mitochondrii is Ixodes ricinus, the predominant tick in Europe and vector of important pathogens that cause a variety of diseases, including Lyme borreliosis and typhus. Understanding the role of Midichloria and its influence on the host physiology could lead to novel strategies to fight this important pathogen vector.

In order to investigate the role of M. mitochondrii we need to describe the lifecycle of this bacterium in the host and to understand its colonization of the mitochondria in the host oocytes. Due to the impossibility to grow it in cell culture, it is not possible to directly observe the lifecycle of M. mitochondrii within a single oocyte: we can only take shots of frozen moments using transmission electron microscopy. The first images acquired by Sacchi and colleagues in 2004, showed that an important portion of the hundreds of mitochondria present in the cells were colonized, and that a colonized mitochondrion can harbour one or more bacteria. This evidence suggested that the bacterium could be able to invade the mitochondrion and replicate within it. Moreover, few mitochondria appeared degraded, suggesting a lifecycle similar to that of predatory bacteria or viruses. 

In this study, we produce microscopy data from tens of oocytes from multiple ticks collected all over Europe. We counted the number of mitochondria and the bacteria colonizing them and used these data to perform mathematical modelling of the lifecycle of the bacterium. Our results show that M. mitochondrii is not detrimental to the tick mitochondria but supports a beneficial role of the bacterium in the host.  The data indicate that M. mitochondrii could not have a lifecycle similar to that of predatory bacteria, invading mitochondria and replicating within them. We thus proposed a novel model of M. mitochondrii lifecycle, coherent with our data, called the “mitochondrion-to-mitochondrion” model: the bacterium is able to move from one mitochondrion to another, inside the connections that these organelles create, the mitochondrial network. This represents an important step forward in the understanding of the Midichloria mitochondrii - mitochondria relationship.

HFSP award information

Research Grant - Early Career  (RGY0075/2017): Midichloria mitochondrii, unique intramitochondrial bacterium and novel tool to explore mitochondria

Principal investigator: Davide Sassera, Pavia University, Italy
Co-investigator 1: Fabrizia Stavru, Pasteur Institute, Paris, France (nationality Italy)
Co-investigator 2: Aaron Jex, The Walter and Eliza Hall Institute, Parkville, Australia
Co-investigator 3: Jan Riemer, Cologne University, Germany

 

Reference

Modeling the Life Cycle of the Intramitochondrial Bacterium "Candidatus Midichloria mitochondrii" Using Electron Microscopy Data
Francesco Comandatore, Giacomo Radaelli, Sebastiano Montante, Luciano Sacchi, Emanuela Clementi, Sara Epis, Alessandra Cafiso, Valentina Serra, Massimo Pajoro, Domenico Di Carlo, Anna Maria Floriano, Fabrizia Stavru, Claudio Bandi, Davide Sassera
mBio. 2021 Jun 29;12(3):e0057421. doi: 10.1128/mBio.00574-21. Epub 2021 Jun 22.

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Reference

Modeling the Life Cycle of the Intramitochondrial Bacterium "Candidatus Midichloria mitochondrii" Using Electron Microscopy Data
Francesco Comandatore, Giacomo Radaelli, Sebastiano Montante, Luciano Sacchi, Emanuela Clementi, Sara Epis, Alessandra Cafiso, Valentina Serra, Massimo Pajoro, Domenico Di Carlo, Anna Maria Floriano, Fabrizia Stavru, Claudio Bandi, Davide Sassera
mBio. 2021 Jun 29;12(3):e0057421. doi: 10.1128/mBio.00574-21. Epub 2021 Jun 22.