Biology subjects

PERRIN, A.

Publications and source records attributed to PERRIN, A..

5 recordsLinked to original sources

bioRxiv2023

Comparative genomics of carbapenemase-producing Morganella spp.

BackgroundMorganella are opportunistic pathogens involved in various infections. In Morganella, intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. MethodsFrom 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A. FindingsMorganella could be separated into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii included two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius. Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five high-risk clones of M. morganii subsp. morganii. A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDR Morganella spp. isolates of our collection (including 145 CP) except for metallo-{beta}-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A. InterpretationThis global characterization of the widest collection of XDR Morganella spp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons. FundingNone RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSOn January 28th 2022, we have searched for the terms "Morganella" and "carbapenemase" in all published reports available in PubMed with no language restriction. We identified a total of 43 articles and most of them (41/43) corresponded to a report of a single isolate of carbapenemase-producing Morganella morganii. Only one article aimed to decipher the antimicrobial susceptibility on a collection of Proteus, Providencia and Morganella isolated from global hospitalized patients with intra-abdominal and urinary tract infections. However, this collection only included 7 M. morganii isolates. On March 2021, when we finished the inclusions in our collection, only 104 genomes of Morganella spp. were available in the NCBI database. Since September 2021, very few reports were published on carbapenemase-producing Morganella with the exception of a study from Xiang G et al. reported 40 multi-drug resistant M. morganii isolates recovered from three hospitals in China from 2014 to 2020. Unfortunately, this collection included only two carbapenemase-producing M. morganii isolates (one OXA-48 and one IMP-1). A report of KPC-producing M. morganii in Japan and a longitudinal study of carbapemase-producing Enterobactrales in Taiwan that did not focused on Morganella. We also searched in PubMed for the terms Morganella sibonii" or "Morganella psychrotolerans" in all published reports with no language restrictions. Our search identified a total of 20 articles. None of them was related to antimicrobial resistance and no study deciphered the Morganella spp. epidemiology on clinical isolates. Added values of this studyThis global characterization involved the widest collection of Morganella spp. isolates ever reported (barely doubling the number of Morganella spp. genomes in Genbank). In addition, 145 isolates of this worldwide collection made of 172 multidrug resistant Morganella spp. were carbapenemase producers for which therapeutic alternatives are scarce due to intrinsic resistance to last resort molecules, such as polymyxin. First, we found that cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards XDR Morganella spp. isolates except for metallo-{beta}-lactamase-producers. Then, we observed that carbapenemase-encoding genes were present in different Morganella species highlighting necessary changes in the taxonomy. Morganella genus could be divided into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii includes two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius. We demonstrated that this refined taxonomy correlated with the intrinsic resistance to tetracycline, which was found only in M. sibonii, as well as several metabolic pathways (e.g. trehalose assimilation, type III (T3SS) and type IV secretion system (T6SS), etc....). In addition, we highlighted five "high-risk" clones of carbapenemase-producing M. morganii subsp. morganii that have already disseminated worldwide. Combining whole genome sequencing (WGS) data with epidemiological investigations, we demonstrated that a cut-off of 100 single nucleotide polymorphisms (SNPs) could be used to discriminate clonally-related from sporadic independent isolates. This information is of the utmost importance since WGS is now considered as the reference method to identify and follow outbreaks. The intrinsic resistance of Morganella spp. to polymyxins was well-known but the underlying mechanism was unclear. Here, we demonstrated that the addition of L-Ara4N on the lipid A of Morganella is involved. Implications of all the available evidenceThe identification of "high-risk" clones among highly-drug resistant Morganella spp. paves the way of future investigations to better understand and hopefully limit the spread of these bugs. Additionally, our results identified new components and virulence factors of some Morganella species (e.g. T6SS and T3SS in M. sibonii) that deserve further investigation since they might be implicated in the bacterial lifestyle of this genus.

microbiology↗

bioRxiv2023

BioConvert: a comprehensive format converter for life sciences

AO_SCPLOWBSTRACTC_SCPLOWBioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiated BioConvert, a collaborative project to facilitate the conversion of life science data from one format to another. BioConvert aggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently, BioConvert supports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users, BioConvert can also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface to BioConvert, hence allowing direct use for the community.

bioinformatics↗

bioRxiv2022

IntegronFinder 2.0: identification and analysis of integrons across Bacteria, with a focus on antibiotic resistance in Klebsiella

Integrons are mobile genetic elements that contain multiple cassettes encoding accessory genes whose order is shuffled by a specific integrase. Integrons within mobile genetic elements often contain multiple antibiotic resistance genes that they spread among nosocomial pathogens and contribute to the current antibiotic resistance crisis. However, most integrons are presumably sedentary and encode a much broader diversity of functions. IntegronFinder is a widely used software to identify novel integrons in bacterial genomes, but has aged and lacks some useful functionalities to handle very large datasets of draft genomes or metagenomes. Here, we present IntegronFinder version 2. We have updated the code, improved its efficiency and usability, adapted the output to incomplete genome data, and added a few novel functions. We describe these changes and illustrate the relevance of the program by analyzing the distribution of integrons across more than 20,000 fully sequenced genomes. We also take full advantage of its novel capabilities to analyze close to 4 thousand Klebsiella pneumoniae genomes for the presence of integrons and antibiotic resistance genes within them. Our data shows that K. pneumoniae has a large diversity of integrons and the largest mobile integron in our database of plasmids. The pangenome of these integrons contains a total of 165 different gene families with most of the largest families being related with resistance to numerous types of antibiotics. IntegronFinder is a free and open-source software available at https://github.com/gem-pasteur/Integron_Finder.

bioinformatics↗

bioRxiv2020

PanACoTA: A modular tool for massive microbial comparative genomics

The study of the gene repertoires of microbial species, their pangenomes, has become a key topic of study in microbial evolution and genomics. Yet, the increasing number of genomes available complicates the establishment of the basic building blocks of comparative genomics. Here, we present PanACoTA (https://github.com/gem-pasteur/PanACoTA), a tool that allows to download all genomes of a species, build a database with those passing quality and redundancy controls, uniformly annotate, and then build their pangenome, several variants of core genomes, their alignments, and a rapid but accurate phylogenetic tree. While many programs building pangenomes have become available in the last few years, we have focused on a modular method, that tackles all the key steps of the process, from download to phylogenetic inference. While all steps are integrated, they can also be run separately and multiple times to allow rapid and extensive exploration of the parameters of interest. The software is built in Python3 and includes features to facilitate its future development. We believe PanACoTa is an interesting addition to the current set of comparative genomics tools, since it will accelerate and standardize the more routine parts of the work, allowing microbial genomicists to more quickly tackle their specific questions.

bioinformatics↗

bioRxiv2020

Mosquito densoviruses: the revival of a biological control agent against urban Aedes vectors of arboviruses

Urban Aedes mosquitoes are vectors of many viruses affecting human health such as Dengue, Chikungunya and Zika viruses. Insecticide resistance and environmental toxicity risks hamper the effectiveness of chemical control against these mosquito vectors. Alternative control methods, such as the use of mosquito-specific entomopathogenic viruses should be explored. Numerous studies have focused on evaluating the potential of different densoviruses species as biological control agent. However, knowledge on the extent of inter- and intra-specific variations in the susceptibility of Aedes mosquitoes to infection by different densoviruses remains insufficient. In this study, we compared infection and mortality rates induced by the Aedes albopictus densovirus 2 in different strains of Aedes albopictus and Aedes aegypti mosquitoes. The two Aedes species were different in terms of susceptibility to viral infection. Under laboratory conditions, Aedes albopictus densovirus 2 appeared more virulent for the different strains of Aedes aegypti tested than for those of Aedes albopictus. In addition, we also found significant intra-specific variation in infection and mortality rates. Thus, although even if Aedes albopictus densoviruses could be powerful biocontrol agents used in the management of urban Aedes populations, our results also call into question the use of single viral isolate as biocontrol agents.

microbiology↗