Midichloria mitochondrii
Midichloria mitochondrii is an intracellular bacterium with a unique lifestyle. Discovered in 2006 by a joint effort of the parasitologists of Pavia and Milano, Midichloria mitochondrii was found to have the remarkable capability to thrive inside the mitochondria of the cells of its host, the medically important tick Ixodes ricinus. Fascinated by this peculiar form of symbiosis, we are using and integrating multiple approaches to try to understand this interaction and its evolution, including molecular biology, genomics, high-resolution microscopy (TEM, FIB- SEM), modelling, and, more recently, in silico protein-protein predictions.
Our current research on Midichloria mitochondrii is focused on investigating the presence and features of the intramitochondrial tropism among relatives of Midichloria mitochondrii in ticks and other hosts in order to trace its evolution, and on understanding its molecular mechanisms by in silico predictions.
Selected published research:
- Modeling the Life Cycle of the Intramitochondrial Bacterium “Candidatus Midichloria mitochondrii” Using Electron Microscopy Data
- The evolution of intramitochondriality in Midichloria bacteria
- Three-dimensional images reveal the impact of the endosymbiont Midichloria mitochondrii on the host mitochondria
- Tissue tropism and metabolic pathways of Midichloria mitochondrii suggest tissue-specific functions in the symbiosis with Ixodes ricinus
Rickettsiales and other bacterial symbionts of eukaryotes
Multiple diverse bacteria engage in complex interaction with as diverse eukaryotes. These interaction involve multifaceted interplays. Along evolution, the mechanisms and effects of pre- existing interactions may vary, as well as the partner specificity of each symbiotic associate. The Rickettsiales are a noteworthy bacterial lineage, being involved since extremely ancient times in association with eukaryotes ranging from amoebas and ciliates to ticks (e.g. Midichloria) and vertebrates, with variegated interaction ranging from benefits for the host (e.g. nutrient provision) to host exploitation by the bacteria, including vector-borne pathogens (e.g. Rickettsia, Anaplasma, Ehrlichia).
We are using genomics and other approaches (transcriptomics, protein-protein interaction predictions) to unveil the evolutionary history and trajectories of Rickettsiales and other lineages of host-associated bacteria, including in particular neglected but evolutionarily significant phylogenetic branches. Our current research is focused on the discovery and analysis of novel lineages, as well as on the evolutionary and functional analyses of host-symbiont interactions.
Selected published research:
- Host association and intracellularity evolved multiple times independently in the Rickettsiales
- Deianiraea, an extracellular bacterium associated with the ciliate Paramecium, suggests an alternative scenario for the evolution of Rickettsiales
- Novel evolutionary insights on the interactions of the Holosporales (Alphaproteobacteria) with eukaryotic hosts from comparative genomics
- Characterization of a novel Pantoea symbiont allows inference of a pattern of convergent genome reduction in bacteria associated with Pentatomidae
- Hepatincolaceae (Alphaproteobacteria) are Distinct From Holosporales and Independently Evolved to Associate With Ecdysozoa
Ticks and tick-borne microorganisms
Ticks are blood-sucking arthropods that represent major vectors of pathogenic microorganisms worldwide, in particular in temperate climates. Vectored pathogens include a variety of protozoa, bacteria, and virus, and may cause severe or even lethal diseases.
We study multiple facets of tick biology and their associated pathogens. These include screening and surveillance of tick-borne pathogens in several tick species and geographic areas, using conventional and innovative (e.g. microfluidic PCR) approaches, (phylo)genetic and genomic investigations on the tick and the pathogens, as well as on the role and evolution of symbiotic bacteria for the tick physiology.
Our current research on this topic is focused on genome-wide population genetic investigations on the main tick European tick vector Ixodes ricinus, and on the bacterium Borrelia burgdorferi sensu lato, causing the Lyme disease.
Selected published research:
- Sequence of a Coxiella Endosymbiont of the Tick Amblyomma nuttalli Suggests a Pattern of Convergent Genome Reduction in the Coxiella Genus
- Tissue tropism and metabolic pathways of Midichloria mitochondrii suggest tissue-specific functions in the symbiosis with Ixodes ricinus
- A dual endosymbiosis supports nutritional adaptation to hematophagy in the invasive tick Hyalomma marginatum
- High-throughput screening of pathogens in Ixodes ricinus removed from hosts in Lombardy, northern Italy
- Multi‐country investigation of the diversity and associated microorganisms isolated from tick species from domestic animals, wildlife and vegetation in selected african countries
- Tick-Borne Encephalitis, Lombardy, Italy
Genomic epidemiology
Genomics can be used to characterize high numbers of isolates of pathogenic bacteria and eukaryotes, using the techniques of genomic epidemiology. By analyzing hundreds and even thousands of genomes, we can reconstruct the epidemiological and evolutionary patterns of these pathogens, reconstructing outbreaks and detailing the evolutionary patterns that led to the emergence of impactful strains. We can in parallel determine the repertoire of genes of interest, such as those responsible for resistance to antimicrobials and for enhanced virulence.
We are currently conducting research on nosocomial pathogenic bacteria (Klebsiella and Acinetobacter) and fungi (Candida), as well as on the widespread protozoal diarrhoeal agent Cryptosporidium.
Selected published research:
- Comparative genomics of Cryptosporidium parvum reveals the emergence of an outbreak-associated population in Europe and its spread to the United States
- Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study
- A large-scale genomic snapshot of Klebsiella spp. isolates in Northern Italy
Development of bioinformatic tools
Bioinformatic approaches and techniques are at the core of genomics and other omic sciences, which are paramount in current biological and biomedical research. Our research group has a strong attitude towards bioinformatics, which we often employ while addressing different research topics and questions (described above).
In this context, we are also targeting the development of bioinformatic methods and tools to allow us and other scientists to address relevant research needs, including availability rapid, user-friendly, and computationally feasible pipelines. As such, we have developed and made available tools for addressing reconstruction of epidemiological outbreaks, of bacterial genomic plasticity, and for screening of predicted protein-protein interactions
Pdor
Publication: P-DOR, an easy-to-use pipeline to reconstruct bacterial outbreaks using genomics
Pippi
Publication: Accelerating protein–protein interaction screens with reduced AlphaFold-Multimer sampling
Fogs – an index to measure bacterial genome plasticity
Publication: How to measure bacterial genome plasticity? A novel time-integrated index helps gather insights on pathogens