Biology subjects

Junier, T.

Publications and source records attributed to Junier, T..

5 recordsLinked to original sources

bioRxiv2025

Fighting Aspergillus infection using biocontrol bacteria: A proof-of-concept of environmental interference in a translational setting

Aspergillus fungi are opportunistic pathogens that affect millions of people worldwide. Aspergilli produce organic acids to optimize the environmental pH and match the needs of their enzymatic machinery. In this study, we tested the hypothesis that this also occurs during infection. By producing oxalic acid (OA), Aspergillus would manipulate pH during lung infection and thus, interfering with this process could control the pathogen. To test this hypothesis, we assessed in silico the potential for OA production in a wide range of Aspergilli. A genetic marker for AO production was detected in most of the species including prevalent human pathogens. We tested OA production in vitro in four strains of A. niger and A. fumigatus, but only one of the A. niger strains produced OA consistently. For this fungal strain, oxalotrophic bacteria were able to control fungal growth via OA consumption. To translate this observation into a pre-clinical system, increasingly complex experiments were performed. In 3D-cell cultures, A. niger also secreted OA and modified pH and free Ca2+. Co-inoculation of the oxalotrophic bacterium inhibited the development of the fungus. However, biocontrol could not be replicated in Galleria mellonella, which is often used as an infection model. In contrast, the bacterium improved disease score and the absence of oxalate crystals in the lungs in the mouse model. This biocontrol interaction between oxalotrophic bacteria and A. niger represents a paradigm shift in the fight against opportunistic fungal pathogens, where the goal is to render the host environment less permissive to pathogen development One Sentence SummaryDemonstration of biocontrol as a therapeutic concept to combat Aspergillus niger with oxalotrophic bacteria in an animal infection model

microbiology↗

bioRxiv2025

Prevalence of Oxalotrophy in the Human Microbiome

Incomplete degradation of oxalate, a compound commonly found in the diet, can cause disease in humans, particularly of the kidney. Its concentration in the body depends on several factors, one of which is intestinal absorption, which is itself affected by oxalotrophy among enteric bacteria. Oxalotrophy in the human microbiome is poorly known. In this study, we perform a systematic search for the simultaneous presence of the three oxalotrophy genes, namely frc, oxc and oxlT. Thanks to the construction and validation of specific conservation models for all three genes, we were able to search for oxalotrophy in genomes and metagenomes associated with the human digestive tract, oral cavity, and lungs. We report that oxalotrophy - the capacity to use oxalate as a source of energy - is a rare metabolic trait, mostly confined to the gut, and also find evidence that it can be acquired by horizontal gene transfer. By contrast, the capacity for oxalate degradation is more widespread, and two genes responsible for it (frc and oxc) are almost always close together in the genome, suggesting selection pressure.

microbiology↗

bioRxiv2022

The butterfly effect: mutational bias of SARS-CoV-2 affects its pattern of molecular evolution on synonymous and nonsynonymous levels

Evolution is a function of mutagenesis and selection. To analyse the role of mutagenesis on the structure of the SARS-CoV-2 genome, we reconstructed the mutational spectrum, which was highly C>U and G>U biased. This bias forces the SARS-CoV-2 genome to become increasingly U-rich unless selection cancels it. We analysed the consequences of this bias on the composition of the most neutral (four-fold degenerate synonymous substitutions) and the least neutral positions (nonsynonymous substitutions). The neutral nucleotide composition is already highly saturated by U and, according to our model, it is at equilibrium, suggesting that in the future, we dont expect any more increase in U. However, nonsynonymous changes continue slowly evolve towards equilibrium substituting CG-rich amino-acids ("losers") with U-rich ones ("gainers"). This process is universal for all genes of SARS-CoV-2 as well as for other coronaviridae species. In line with the direction mutation pressure hypothesis, we show that viral-specific amino acid content is associated with the viral-specific mutational spectrum due to the accumulation of effectively neutral slightly deleterious variants (losers to gainers) during the molecular evolution. The tuning of a protein space by the mutational process is expected to be typical for species with relaxed purifying selection, suggesting that the purging of slightly-deleterious variants in the SARS-CoV-2 population is not very effective, probably due to the fast expansion of the viral population during the pandemic. Understanding the mutational process can help to design more robust vaccines, based on gainer-rich motifs, close to the mutation-selection equilibrium.

evolutionary biology↗

bioRxiv2020

Cryptosporulation in Kurthia spp. forces a rethinking of asporogenesis in Firmicutes

Sporulation is a complex morphophysiological process resulting in a cellular structure that is more resistant than the vegetative form. In Firmicutes, this structure is produced within the mother cell, and is called an endospore. Endospore formation is thought to have evolved in the common ancestor of Firmicutes. However, sporulation has apparently been lost in some extant lineages that are defined as asporogenic. We isolated strain 11kri321, a representative of the genus Kurthia, from an oligotrophic geothermal reservoir. While Kurthia spp. is considered to comprise only asporogenic species, strain 11kri321 produced spores. Genomic reconstruction of the sporulation pathway shows elements typical of sporulation in Bacilli, including the signaling for sporulation onset. However, key genes were missing, including those involved in engulfment and dipicolinic acid synthesis. Based on the results for strain 11kri321, sporulation was investigated in other Kurthia strains. Genes involved in signaling, cell division and spore coat formation were detected in three available Kurthia genomes. Moreover, endosporulation was clearly visualized in at least two of the four strains tested. These results show that Kurthia is an endospore-forming Firmicute lineage. However, the genetic background of sporulation in this genus deviates from the known sporulation pathway in Firmicutes and even within Bacilli, suggesting that a revision of the minimal set of genes used for genomic detection of sporulation is required. Based on our findings we propose the term cryptosporulant to refer to putative asporogenic Firmicutes for which a detailed genomic and physiological characterization of sporulating is missing. ImportanceEndospore-forming Firmicutes include many environmental and medical relevant bacterial clades. In these microorganisms, the ability to produce endospores is essential for survival in the environment and even for pathogenesis. The minimum core of genes required to produce a viable and resistant spore, the distinction between endospore-forming and asporogenic groups, as well as the evolution of sporulation have been a subject of investigation and debate for decades. Here, we demonstrate endosporulation in the genus Kurthia, considered as asporogenic. Morphological, physiological and genomic analyses were undertaken to demonstrate that sporulation is not lost within this lineage. Based on our results we propose a re-examination of the minimal genetic requirements of sporulation and the use of the term cryptosporulant to describe lineages of Firmicutes that have not previously been observed to sporulate, but for which a detailed analysis is still missing.

microbiology↗

bioRxiv2019

Genomics of Human Respiratory Syncytial Virus Vaccine Attenuation

The human orthopneumovirus (HRSV) is a major cause of lower respiratory tract infection in children worldwide. Despite decades of efforts, no vaccine is available. In this work, we report mutations that are frequent in vaccine candidates and rare in wild-type genomes, taking into account all the publicly available HRSV sequence data. These mutations are different from the ones already known to attenuate the virus, and thus may contribute to the effort towards producing a live attenuated vaccine against HRSV.

genomics↗