Biology subjects

Cabanel, N.

Publications and source records attributed to Cabanel, N..

6 recordsLinked to original sources

bioRxiv2026

Spatiotemporal dynamics of β-lactam-resistant E. coli in young diseased calves in Wallonia, Belgium

Calves are one of the most common carriers of antibiotic-resistant bacteria among farm animals. However, the impact of antibiotic usage on resistance mechanisms, transmission routes between farms, and the transmission of resistant bacteria to humans remain largely unknown. Here we analyzed the population of {beta}-lactam resistant E. coli isolated over five calving seasons on 444 farms scattered throughout Wallonia, Belgium. Restrictions on critical antibiotics usage led to a reduction of resistance to 3rd generation cephalosporins but has no impact on population structure and {beta}-lactamase genes indicating a resilient population. The correlation between short genetic distances and geographic proximity suggests indirect transmission between farms by fomites with differences between regions east and west of the river Meuse. Phylogenetic analysis of calf isolates with isolates from public databases indicates transitions from bovine to human adaptation. These findings provide new means to further model the spread of E. coli in livestock farming.

microbiology↗

bioRxiv2024

In-host evolution of Yersinia enterocolitica during a chronic human infection

Following a pacemaker implantation, a 75-years-old patient suffered from five successive bacteremia episodes between in 1999 and 2013 despite long-term antibiotic treatment, with intermittent vegetation apparition on the device atrial lead. Four blood isolates, identified as Yersinia enterocolitica bioserotype 4/O:3, were further genetically and phenotypically characterized. Phylogenetic reconstruction showed that the patient was chronically infected by the same strain, which evolved within the host for 14 years. Single-nucleotide polymorphism (SNP) analysis indicates that the last two isolates evolved in parallel and formed two independent lineages within the host. Pan-genome analysis and genome comparison showed that their common evolution was characterized by 41 small insertion/deletion events, loss of three large DNA fragments and mutations in 140 genes. A phylogenetic analysis by maximum likelihood identified two genes presenting a positive selection signal, suggesting that these mutations provided a survival advantage to bacteria during chronic infection. Quinolone resistance in the last two isolates was acquired through a so far undescribed deletion in the gyrA gene. Mass-spectrometry analysis revealed a strong proteome remodeling in the last two isolates which was correlated with a truncation in the stringent response regulator DksA. A reduced carbon, energy and purine metabolism supports their severe growth defects in vitro. 3rd-generation cephalosporin resistance of the last isolate was correlated with a truncation of OmpF, the main porin translocating antibiotics through the outer-membrane, as well as an increased production of BlaA and AmpC {beta}-lactamases. This is the first report of genetic and phenotypic changes associated to within-host adaptation of a pathogenic Yersinia species under antibiotic pressure.

microbiology↗

bioRxiv2022

Carbapenem heteroresistance of KPC-producing Klebsiella pneumoniae results from tolerance, persistence and resistance.

Carbapenemase-producing Klebsiella pneumoniae (CPKp) have disseminated globally and represent a major threat in hospitals with few therapeutic options and high mortality rates. Isolates producing the carbapenemase KPC (KPC-Kp) might be classified as susceptible according to clinical breakpoints by antibiotic susceptibility testing (AST), allowing the use of imipenem or meropenem for treatment of infections. However, some KPC-Kp show heteroresistance (HR) to carbapenems, with colonies growing in the inhibition halo of agar-based AST. HR KPC-Kp have been associated with a higher risk of treatment failure. Here, we characterized the diversity of mechanisms behind HR to imipenem of these isolates. By analyzing a diverse collection of CPKp, we showed that HR is frequent among KPC-Kp. By monitoring single HR colony appearance using the ScanLag setup, we discriminated surviving cells in two subpopulations leading to a Gaussian-like distribution of early-appearing colonies, with a delayed emergence compared to colonies arising in the absence of antibiotics, and a long tail of late-appearing colonies. A subset of colonies showed a reduced growth rate. Characterization of surviving populations by AST and whole-genome sequencing of 333 colonies revealed a majority of parental genotypes and a broad landscape of genetic alterations in 28% of the colonies, including gene loss, DNA amplification and point mutations. This unveils the complexity of imipenem HR among KPC-Kp isolates, which involves tolerant and persistent cells, but also resistant bacteria. These observations contribute to a better understanding of reasons behind carbapenem treatment failure of KPC-Kp isolates. IMPORTANCEThe ability of a bacterium to defeat antibiotics not only depends upon resistance, but also on tolerance and persistence, which allow a bacterial population to temporarily survive high drug doses. Carbapenems are antibiotics of last resort and Klebsiella pneumoniae isolates producing the carbapenemase KPC are a threat to hospitals, although they might remain susceptible to carbapenems. However, seemingly homogeneous populations of KPC-K. pneumoniae isolates frequently show varying degrees of susceptibility to carbapenem, i.e., a phenomenon called heteroresistance. We characterized bacteria surviving a high dose of imipenem, progressively degraded by the released carbapenemase, by monitoring the growth of the resulting colonies using the ScanLag system, their genome sequence and carbapenem susceptibility. We show that the observed phenotypic diversity combines tolerance, persistence and resistance making the treatment with high doses of carbapenems frequently inefficient.

microbiology↗

bioRxiv2021

Specificities and commonalities of carbapenemase producing Escherichia coli isolated in France from 2012 to 2015.

Carbapenemase-producing Escherichia coli (CP-Ec) represent a major public health threat with a risk of dissemination in the community as it has occurred for lineages producing extended spectrum {beta}-lactamases. To characterize the extend of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Centre laboratory (F-NRC) for carbapenemase-producing Enterobacterales were investigated. Six hundred and ninety one CP-Ec isolates collected between 2012 and 2015 and 22 before were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex (CC) 23 (ST 410) and CC10 (ST10, ST167) and sporadic isolates including rare ST131 isolates (n=17). However, the most represented ST was ST38 (n=92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n=457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast blaOXA-181 or blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC. IMPORTANCECarbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as minimal inhibitory concentrations can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast carbapenemase gene transfer may also occur in multi-drug resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.

microbiology↗

bioRxiv2021

Evolution of VIM-1 producing Klebsiella pneumoniae isolates from a hospital outbreak reveals the genetic bases of the loss of the urease-positive identification character

Outbreaks of carbapenemase producing Klebsiella pneumoniae (CPKp) represent a major threat for hospitals. We molecularly characterized the first outbreak of VIM-1 producing K. pneumoniae in Spain, that raised fears about the spread of this strain or of the plasmid carrying blaVIM-1. Through in-depth genomic analysis of 18 isolates recovered between October 2005 and September 2007, we show that 17 ST39 isolates were clonal, whereas the last isolate had acquired the VIM-1 plasmid from the epidemic clone. The index isolate carried 31 antibiotic resistance genes (ARGs) and was resistant to almost all antibiotics tested. Later isolates further gained mutations in efflux pumps regulators ramR and opxR, deletion of mgrB (colistin resistance) and frameshift mutations in ompK36 ({beta}-lactam resistance) likely selected by antibiotic usage. Comparison with publicly available genome sequences and literature review revealed no sign of dissemination of this CPKp strain. However, the VIM-1 plasmid was found in diverse Enterobacterales species, although restricted to Spain. One isolate became urease negative following IS5075 transposition into ureC. Analysis of 9755 K. pneumoniae genomes showed the same ureC::IS5075 insertion in 14.1% of the isolates and explained why urease activity is a variable identification trait for K pneumoniae. Transposition into ureC results from the similarity of its 3-end and the terminal inverted repeats of Tn21 like transposons, the targets of IS5075 and related ISs. As these transposons frequently carry ARGs, this might explain the frequent chromosomal invasion by these ISs and ureC inactivation in multidrug resistant isolates. IMPORTANCEEvolution of multidrug resistant bacterial pathogens occurs at multiple scales, in the patient, locally in the hospital or more globally. Some mutations or gene acquisitions, for instance in response to antibiotic treatment, may be restricted to a single patient due to their high fitness cost. However, some events are more general. By analyzing the evolution of a hospital acquired multidrug resistant K. pneumoniae strain producing the carbapenemase VIM-1, we showed a likely environmental source in the hospital and identified mutations contributing to a further decrease in antibiotic susceptibility. By combining the genomic analysis of this outbreak with literature data and genome sequences available in databases, we showed that the VIM-1 plasmid has been acquired by different Enterobacterales but is only endemic in Spain. We also discovered that urease loss in K. pneumoniae results from the specific transposition of an IS element into the ureC gene and was more frequent in fluoroquinolone resistant isolates and carrying a carbapenemase gene.

evolutionary biology↗

bioRxiv2018

Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli

Carbapenem-resistant Enterobacteriaceae are considered by WHO as \"critical\" priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producing Escherichia coli (CP-Ec) in the community is a major public health concern. However, the global molecular epidemiology of CP-Ec isolates, as well as the genetic bases for the emergence and global dissemination of specific lineages, remain largely unknown. Here, by combining a thorough genomic and evolutionary analysis of Ec ST410 isolates with a broad analysis of 12,584 E. coli and Shigella genomes, we showed that the fixation of carbapenemase genes depends largely on a combination of mutations in ftsI encoding the penicillin binding protein 3 and in the porin genes ompC and ompF. Mutated ftsI genes and a specific ompC allele inducing reduced susceptibility to diverse {beta}-lactams spread across the species by recombination. The selection of CP-Ec lineages able to disseminate is more complex than the mere acquisition of carbapenemase genes.

microbiology↗