Biology subjects

Decousser, J.-W.

Publications and source records attributed to Decousser, J.-W..

3 recordsLinked to original sources

bioRxiv2021

Chlorhexidine reduced susceptibility associated to tetracycline resistance in clinical isolates of Escherichia coli

Chlorhexidine is a widely used antiseptic in hospital and community healthcare. Decreased susceptibility to this compound has been recently described in Klebsiella pneumoniae and Pseudomonas aeruginosa, together with cross-resistance to colistin. Surprisingly, few data are available for Escherichia coli, the main species responsible for community and healthcare-associated infections. In order to decipher chlorhexidine resistance mechanisms in E. coli, we studied both in vitro derived and clinical isolates through whole-genome sequence analysis. Comparison of strains grown in vitro under chlorhexidine pressure identified mutations in the gene mlaA coding for a phospholipid transport system. Phenotypic analyses of single-gene mutant from the Keio collection confirmed the role of this mutation in the decreased susceptibility to chlorhexidine. However, mutations in mlaA were not found in isolates from large clinical collections. In contrast, genome wide association studies (GWAS) showed that, in clinical strains, chlorhexidine reduced susceptibility was associated with the presence of tetA genes of class B coding for efflux pumps and located in a Tn10 transposon. Construction of recombinant strains in E. coli K-12 confirmed the role of tetA determinant in acquired resistance to both chlorhexidine and tetracycline. Our results reveal two different evolutionary paths leading to chlorhexidine decreased susceptibility: one restricted to in vitro evolution conditions and involving a retrograde phospholipid transport system; the other observed in clinical isolates associated with efflux pump TetA. None of these mechanisms provides cross-resistance to colistin or to the cationic surfactant octenidine. This work demonstrates the GWAS power to identify new resistance mechanisms in bacterial species.

microbiology↗

bioRxiv2021

The population genomics of increased virulence and antibiotic resistance in human commensal Escherichia coli over 30 years in France

Escherichia coli is a commensal species of the lower intestine, but also a major pathogen causing intestinal and extra-intestinal infections, increasingly prevalent and resistant to antibiotics. Most studies on genomic evolution of E. coli used isolates from infections. Here instead, we whole-genome sequenced a collection of 403 commensal E. coli isolated from fecal samples of healthy adult volunteers in France (1980-2010). These isolates were distributed mainly in phylogroups A and B2 (30% each) and belonged to 152 sequence types (STs), the five most frequent being ST10 (phylogroup A) (16.3%), ST73 and ST95 (phylogroup B2) (6.3 and 5.0%, respectively), ST69 (phylogroup D) (4.2%) and ST59 (phylogroup F) (3.9%), and 224 O:H serotypes. ST and serotype diversity increased over time. The O1, O2, O6 and O25-groups used in bioconjugate O-antigen vaccine against extra-intestinal infections were found in 23% of the strains of our collection. The increase in frequency of virulence-associated genes and antibiotic resistances was driven by two evolutionary mechanisms. Evolution of virulence gene frequency was driven by both clonal expansion of STs with more virulence genes ("ST-driven") and increases in gene frequency within STs independently of changes in ST frequencies ("gene-driven"). In contrast, the evolution of resistance was dominated by increases in frequency within STs ("gene-driven"). This study provides a unique picture of the phylogenomic evolution of E. coli in its human commensal habitat over 30 years and will have implications for the development of preventive strategies. IMPORTANCEEscherichia coli is an opportunistic pathogen with the greatest burden of antibiotic resistance, one of the main causes of bacterial infections and an increasing concern in an ageing population. Deciphering the evolutionary dynamics of virulence and antibiotic resistance in commensal E. coli is important to understand adaptation and anticipate future changes. The gut of vertebrates is the primary habitat of E. coli and probably where selection for virulence and resistance take place. Unfortunately, most whole-genome sequenced strains are isolated from pathogenic conditions. Here, we whole genome sequenced 403 E. coli commensals isolated from healthy French subjects on a 30-year period. Virulence genes increased in frequency by both clonal expansion of clones carrying them and increases in frequency within clones whereas resistance genes increased by within clone increased frequency. Prospective studies of E. coli commensals should be performed worldwide to have a broader picture of evolution and adaptation of this species.

genomics↗

bioRxiv2018

PlaScope: a targeted approach to assess the plasmidome of Escherichia coli strains

Plasmid prediction may be of great interest when studying bacteria such as Enterobacteriaceae. Indeed many resistance and virulence genes are located on such replicons and can have major impact in terms of pathogenicity and spreading capacities. Beyond strains outbreak, plasmids outbreaks have been reported especially for some extended-spectrum beta-lactamase or carbapenemase producing Enterobacteriaceae. Several tools are now available to explore the \"plasmidome\" from whole-genome sequence data, with many interesting and various approaches. However recent benchmarks have highlighted that none of them succeed to combine high sensitivity and specificity. With this in mind we developed PlaScope, a targeted approach to recover plasmidic sequences in Escherichia coli. Based on Centrifuge, a metagenomic classifier, and a custom database containing complete sequences of chromosomes and plasmids from various curated databases, it performs a classification of contigs from an assembly according to their predicted location. Compared to other plasmid classifiers, Plasflow and cBar, it achieves better recall (0.87), specificity (0.99), precision (0.96) and accuracy (0.98) on a dataset of 70 genomes containing plasmids. Finally we tested our method on a dataset of E. coli strains exhibiting an elevated rate of extended-spectrum beta-lactamase coding gene chromosomal integration, and we were able to identify 20/21 of these events. Moreover virulence genes and operons predicted locations were also in agreement with the literature. Similar approaches could also be developed for other well-characterized bacteria such as Klebsiella pneumoniae.\n\nData summaryO_LIAll the genomes were downloaded from the National Center for Biotechnology Information Sequence Read Archive and Genome database (Supplementary table 1 and 2).\nC_LIO_LIThe source code of PlaScope is available on Github (https://github.com/GuilhemRoyer/PlaScope).\nC_LI\n\nImportancePlasmid exploration could be of great interest since these replicons are pivotal in the adaptation of bacteria to their environment. They are involved in the exchange of many genes within and between species, with a significant impact on antibiotic resistance and virulence in particular. However, plasmid characterization has been a laborious task for many years, requiring complex conjugation or electroporation manipulations for example. With the advent of whole genome sequencing techniques, access to these sequences is now potentially easier provided that appropriate tools are available. Many softwares have been developed to explore the plasmidome of a large variety of bacteria, but they rarely managed to combine sensitivity and specificity. Here, we focus on a single species, E. coli, and we use the many data available to overcome this problem. With our tool called PlaScope, we achieve high performance compared with two other classifiers, Plasflow and cBar, and we demonstrate the utility of such an approach to determine the location of virulence or resistance genes. We think that PlaScope could be very useful in the analysis of specific and well-known bacteria.

bioinformatics↗