Biology subjects

Mallet, L.

Publications and source records attributed to Mallet, L..

4 recordsLinked to original sources

bioRxiv2021

Intracellular Salmonella Paratyphi A is motile and differs in the expression of flagella-chemotaxis, SPI-1 and carbon utilization pathways in comparison to Intracellular S. Typhimurium

Although Salmonella Typhimurium (STM) and Salmonella Paratyphi A (SPA) belong to the same phylogenetic species, share large portion of their genome and express many common virulence factors, they differ vastly in their host specificity, the immune response they elicit, and the clinical manifestations they cause. In this work, we compared for the first time their intracellular trascriptomic architecture and cellular phenotypes during epithelial cell infection. While transcription induction of many metal transport systems, purines, biotin, PhoPQ and SPI-2 regulons was common in both intracellular SPA and STM, we identified 234 differentially expressed genes that showed distinct expression patterns in intracellular SPA vs. STM. Surprisingly, clear expression differences were found in SPI-1, motility and chemotaxis, and carbon (mainly citrate, galactonate and ethanolamine) utilization pathways, indicating that these pathways are regulated and possibly function differently, during their intracellular phase. Moreover, we show that the induction of flagella genes by intracellular SPA leads to cytosolic motility, a conserved trait specific to SPA. To the best of our knowledge, this is the first report of a flagellum-dependent intracellular motility of any Salmonella serovar in living host cells. Importantly, we demonstrate that the elevated expression of SPI-1 and motility genes by intracellular SPA results in increased invasiveness of SPA, following exit from host cells. We propose that such changes prime SPA towards new cycles of host cell infection and contribute to the ability of SPA to disseminate beyond the intestinal lamina propria of the human host, during enteric fever. IMPORTANCESalmonella enterica is a ubiquitous, facultative intracellular animal and human pathogen. Although non-typhoidal Salmonella (NTS) and typhoidal Salmonella serovars belong to the same phylogenetic species and share many virulence factors, the disease they cause in humans is very different. While the underlying mechanisms for these differences are not fully understood, one possible reason expected to contribute to their different pathogenicity is a distinct expression pattern of genes involved in host-pathogen interactions. Here, we compared the global gene expression and the intracellular behavior, during epithelial cell infection of S. Paratyphi A (SPA) and S. Typhimurium (STM), as prototypical serovars of typhoidal and NTS, respectively. Interestingly, we identified different expression patterns in key virulence and metabolic pathways, together with intracellular motility and increased invasiveness of SPA, following exit from infected cells. We hypothesize that these differences are pivotal to the invasive and systemic disease developed following SPA infection in humans.

microbiology↗

bioRxiv2020

The Sapap3-knockout mouse model manifests a spectrum of repetitive behaviours

Symptom comorbidity is present amongst neuropsychiatric disorders with repetitive behaviours, complicating clinical diagnosis and impeding appropriate treatments. This is of particular importance for obsessive-compulsive disorder (OCD) and Tourette syndrome. Here, we meticulously analysed the behaviour of Sapap3 knockout mice, the recent rodent model predominantly used to study compulsive-like behaviours, and found that its behaviour is more complex than originally and persistently described. Indeed, we detected previously unreported elements of distinct pathologically repetitive behaviours, which do not form part of rodent syntactic cephalo-caudal self-grooming. These repetitive behaviours include sudden, rapid body and head twitches, resembling tic-like movements. We also observed that another type of repetitive behaviours, aberrant hindpaw scratching, is responsible for the flagship-like skin lesions of this mouse model, rather than originally suspected self-grooming. In order to characterize the symptomatological nature of observed repetitive behaviours, we pharmacologically challenged these phenotypes by systemic aripiprazole administration, a first-line treatment for tic-like symptoms in Tourette Syndrome and trichotillomania. A single treatment of aripiprazole significantly reduced the number of tic-like movements but not syntactic grooming events. These observations are in line with the high comorbidity of tic- and compulsive-like symptoms in Tourette, OCD and trichotillomania patients as well as with the hypothesis of shared neurobiological mechanisms.

neuroscience↗

bioRxiv2019

A cross-species assessment of cognitive flexibility in compulsive disorders

BackgroundCompulsive behaviors, one of the core symptoms of Obsessive-Compulsive Disorder (OCD), are defined as repetitive behaviors performed through rigid rituals. The lack of behavioral flexibility has been as being one of the primary causes of compulsions, but studies exploring this dimension have shown inconsistencies in different tasks performed in human and animal models of compulsive behavior. The aim of this study was so to assess the involvement of behavioral flexibility in compulsion, with a similar approach across different species sharing a common symptom of compulsivity.\n\nMethods40 OCD patients, 40 healthy individually matched control subjects, 26 C57BL/6J Sapap3 KO mice and 26 matched wildtype littermates were included in this study. A similar reversal learning task was designed to assess behavioral flexibility in parallel in these two species.\n\nResultsWhen considered as homogeneous groups, OCD patients and KO mice expressing compulsive behaviors did not significantly differ from their controls regarding behavioral flexibility. When clinical subtypes were considered, only patients exhibiting checking compulsions were impaired with more trials needed to reach the reversal criterion. In KO mice, a similarly impaired subgroup was identified. For both species, this impairment did not result in a greater perseveration after reversal, but in a greater lability in their responses in the reversal condition. Moreover, this impairment did not correlate with the severity of compulsive behaviors.\n\nConclusionsIn our cross-species study, we found no consistent link between compulsive behaviors and a lack of behavioral flexibility. However, we showed in both species that the compulsive group was heterogeneous in term of performance in our reversal learning task. Among the compulsive subjects, we identified a subgroup with impaired performance not due to perseverative and rigid behaviors as commonly hypothesized, but rather to an increase in response lability.

neuroscience↗

bioRxiv2017

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the first, 2GB genome of a cockroach, Blattella germanica, and the 1.3GB genome of the drywood termite, Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

evolutionary biology↗