The use of antibiotics disrupts the gut microbiota, potentially leading to long-term health issues and the spread of resistance. To investigate the impact of antibiotics on phage populations, we followed 22 healthy individuals two weeks before and up to six months after a three-day course of 3rd-generation cephalosporins. The populations of phages encoded very rarely antibiotic resistance genes and were mostly temperate including many phage-plasmids. Moreover, gut phages remained individual-specific even after microbiome perturbation by antibiotics. Yet, we found a 20% decline in phage diversity and abundance, which took 30 days to recover, and a few (mostly virulent) phages burst the day after treatment. We suggest they contribute to the recovery of gut bacterial diversity, since several targeted Parabacteroides distasonis, a bacterium thriving after cephalosporin treatment, which only proliferated in the absence of these phages. Our findings point out that phages play a crucial role in the gut microbiota's response to antibiotics by restoring microbial balance and diversity. ### Competing Interest Statement The authors have declared no competing interest.

Antibiotic use disrupts the gut microbiota, posing risks of long-term health issues and resistance. To study its impact on gut phages, we followed 22 healthy individuals 2 weeks before and up to 6 months after a 3-day course of 3rd-generation cephalosporins. Our results show that gut phages rarely encode antibiotic resistance genes and are mostly temperate, including many phage plasmids. Furthermore, phage populations remain individual-specific even after microbiome perturbation. Yet, we report a 20% decline in phage diversity the day after treatment, alongside blooms of a few, mostly virulent, phages. We suggest that some of these phages contribute to the recovery of bacterial diversity via "kill-the-winner" dynamics. This is supported by (temporarily) dominant phages targeting Parabacteroides distasonis, a bacterium that thrives post-treatment only in the absence of these phages. Our findings suggest gut phages are crucial to the microbiome response to antibiotics, aiding the restoration of balance and diversity.

Escherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary commensal niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli isolates from 22 stools sampled during a 20-year period from a healthy man (ED) living in Paris, France. All phylogroups, except C, were represented, with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty-five clones were identified based on their haplogroup and pairwise genomic single nucleotide polymorphism distance and classified in three phenotypes according to their abundance and residence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four over five dominant/resident clones belonged to B2 and closely related F phylogroups, whereas sub-dominant/transient clones belonged mainly to B1, A and D phylogroups. The long residence times of B2 clones seemed to be counterbalanced by lower colonization abilities. Clones with larger within-host frequency persisted for longer. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, we identified ED-specific genomic properties including an enrichment in genes involved in a metabolic pathway (mhp cluster) and the presence of a very rare antiviral defense island. The E. coli colonization within the gut microbiota was shaped by both the intrinsic properties of the strain lineages, in particular longer residence of phylogroup B2, and the environmental constraints such as diet or phages.

Escherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli natural isolates from 22 stools sampled during a 20-year period in a healthy man (ED) living in France, who did not take any antibiotics. All the phylogroups, except the C, were represented with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty five clones were identified and classified in three phenotypes according to their abundance and persistence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four out of the five dominant/resident clones belonged to B2 phylogroup [sequence types (STs)131 and 452] and F-ST59, whereas sub-dominant/transient clones belonged mainly to numerous distinct B1, A and D phylogroup STs. The long residence time of B2 phylogroup clones was counterbalanced by lower colonization ability. Residence time and within-host frequency were positively correlated. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, enriched/specific ED strain genome traits were identified including a metabolic pathway ( mhp cluster) and a very rarely reported antiviral defense island encompassing dGTPase and/or Detocs systems. SNP analysis of clonal diversity showed neutral evolution. The normal E. coli gut microbiota is shaped by both the intrinsic properties of the strain lineages and the environmental constraints. ### Competing Interest Statement The authors have declared no competing interest.

Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon.

BACKGROUND:Escherichia coli is frequently responsible for bloodstream infections (BSIs). Among digestive BSIs, biliary infections appear to be less severe. Respective roles of host factors, bacterial determinants (phylogroups, virulence, and antibiotic resistance), and portal of entry on outcome are unknown. METHODS:Clinical characteristics and prognosis of 770 episodes of E coli BSI were analyzed and isolates sequenced (Illumina technology) comparing phylogroups, multilocus sequence type, virulence, and resistance gene content. BSI isolates were compared with 362 commensal E coli from healthy subjects. RESULTS:Among 770 episodes, 135 were biliary, 156 nonbiliary digestive, and 479 urinary. Compared to urinary infections, BSIs of digestive origin occurred significantly more in men, comorbid, and immunocompromised patients. Digestive portal of entry was significantly associated with septic shock and death. Among digestive infections, patients with biliary infections were less likely to die (P = .032), despite comparable initial severity. Biliary E coli resembled commensals (phylogroup distribution, sequence type, and few virulence-associated genes) whereas nonbiliary digestive and urinary strains carried many virulence-associated genes. CONCLUSIONS:Escherichia coli strains responsible for biliary infections exhibit commensal characteristics and are associated with lower mortality rates, despite similar initial severity, than other digestive BSIs. Biliary drainage in addition to antibiotics in the management of biliary infections may explain improved outcome.

Escherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary commensal niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli isolates from 22 stools sampled during a 20-year period from a healthy man (ED) living in Paris, France. All phylogroups, except C, were represented, with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty-five clones were identified based on their haplogroup and pairwise genomic single nucleotide polymorphism distance and classified in three phenotypes according to their abundance and residence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four over five dominant/resident clones belonged to B2 and closely related F phylogroups, whereas sub-dominant/transient clones belonged mainly to B1, A and D phylogroups. The long residence times of B2 clones seemed to be counterbalanced by lower colonization abilities. Clones with larger within-host frequency persisted for longer in the host. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, we identified ED-specific genomic properties including a set of genes involved in a metabolic pathway (mhp cluster) and a very rare antiviral defense island. The E. coli colonization within the gut microbiota was shaped by both the intrinsic properties of the strain lineages, in particular longer residence of phylogroup B2, and the environmental constraints such as diet or phages.

It has been shown that an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions contributes to global plasmid fitness. As conjugative IncC plasmids are important for the spread of multidrug resistance (MDR), in a broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two multidrug-resistant IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome deletions after conjugation in three diverse natural Escherichia coli clinical strains, varying from null to high number depending on the plasmid, all occurring in the MDR region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR region, with deletions appearing to have no impact. Besides, we observed an increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, using a second set of conjugation experiments, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment in E. coli K-12, by correlating the transfer rates of deleted or non-deleted IncC plasmids and their costs on the recipient strain. Plasmid deletions strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes. In a broader view, they suggest that the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.

Objective Whole genome sequencing (WGS) of extended-spectrum β-lactamase-producing Escherichia coli (ESBL- E. coli ) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL- E. coli faecal isolates in rural Southern Niger.Methods Stools of 383 healthy participants were collected among which 92.4% were ESBL- E. coli carriers; 90 of these ESBL- E. coli containing stools (109 ESBL- E. coli isolates) were further analysed by WGS, using short- and long-reads.Results Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The bla CTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, bla CTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of bla CTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.Conclusions Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of bla CTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.### Competing Interest StatementThe authors have declared no competing interest.

Objective: Whole genome sequencing (WGS) of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger. Methods: Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads. Results: Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The bla(CTX-M-15) gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, bla(CTX-M-15) was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of bla(CTX-M-15) in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome. Conclusions: Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of bla(CTX-M-15). Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage. (c) 2023 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

AbstractEscherichia coliis both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostics, prevention and treatment is still lacking. We used a collection of 1282 BSI and commensalE. coliisolates collected in France over a 17-year period (2000-2017) and we compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity increased steadily from 23% in 1980 to 46% in 2010. Together our findings imply thatE. coliexhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.

The intrinsic virulence of extra-intestinal pathogenic Escherichia coli is associated with numerous chromosomal and/or plasmid-borne genes, encoding diverse functions such as adhesins, toxins, and iron capture systems. However, the respective contribution to virulence of those genes seems to depend on the genetic background and is poorly understood. Here, we analyze genomes of 232 strains of sequence type complex STc58 and show that virulence (quantified in a mouse model of sepsis) emerged in a sub-group of STc58 due to the presence of the siderophore-encoding high-pathogenicity island (HPI). When extending our genome-wide association study to 370 Escherichia strains, we show that full virulence is associated with the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their co-occurrence and their genomic location depend on strain phylogeny. Thus, selection of lineage-dependent specific associations of virulence-associated genes argues for strong epistatic interactions shaping the emergence of virulence in E. coli .

Multiresistance plasmids belonging to the IncI incompatibility group have become one of the most pervasive plasmid types in extended-spectrum beta-lactamase-producing Escherichia coli of animal origin. The extent of the burden imposed on the bacterial cell by these plasmids seems to modulate the emergence of "epidemic" plasmids. However, in vivo data in the natural environment of the strains are scarce. Here, we investigated the cost of a blaCTX-M-1-IncI1 epidemic plasmid in a commensal E. coli animal strain, UB12-RC, before and after oral inoculation of 15 6- to 8-week- old specific-pathogen-free pigs. Growth rate in rich medium was determined on (i) UB12-RC and derivatives, with or without plasmid, in vivo and/or in vitro evolved, and (ii) strains that acquired the plasmid in the gut during the experiment. Although blaCTX-M-1-IncI1 plasmid imposed no measurable burden on the recipient strain after conjugation and during the longitudinal carriage in the pig's gut, we observed a significant difference in the bacterial growth rate between IncI1 plasmid-carrying and plasmid-free isolates collected during in vivo carriage. Only a few mutations on the chromosome of the UB12-RC derivatives were detected by whole-genome sequencing. RNA-Seq analysis of a selected set of these strains showed that transcriptional responses to the blaCTX-M-1-IncI1 acquisition were limited, affecting metabolism, stress response, and motility functions. Our data suggest that the effect of IncI plasmid on host cells is limited, fitness cost being insufficient to act as a barrier to IncI plasmid spread among natural population of E. coli in the gut niche.

Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostic, prevention and treatment is still lacking. We used a collection of 912 BSI and 370 commensal E. coli isolates collected in France over a 17-year period (2000-2017). We compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity continuously increased through 1980, 2000, to 2010. Together our findings imply that E. coli exhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.

Abstract Background Antibiotics notoriously perturb the gut microbiota. We used untargeted and targeted phenotypic and genotypic approaches to study faecal samples collected up to 90 days following a 3-day course of intravenous β-lactam antibiotics in 22 healthy volunteers. We studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. Results While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the taxonomic composition of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The richness of the resistome was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. Conclusions In healthy adults, antibiotics perturb all the components of the microbiota, which mostly return to its baseline state within 30 days. These data suggest an important role of endogenous β-lactamases producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon.

AbstractThe intrinsic virulence of extra-intestinal pathogenicEscherichia coliis attributed to numerous chromosome and/or plasmid-borne virulence associated genes (VAGs), encoding diverse functions as adhesins, toxins, protectins and iron capture systems, which occur in specific genetic backgrounds. Little is however known on their respective contribution to virulence. Here, by analyzing genomes of 232 sequence type complex (STc) 58 strains, we show that virulence quantified in a mouse model of sepsis emerged in a sub-group of STc58 due to the presence of the siderophore encoding high-pathogenicity island (HPI). When extending our analysis to 370Escherichiastrains we show that full virulence is associated with the presence of theaerorsitoperons, in addition to the HPI. The prevalence of these operons, their co-occurrence and genomic location depend on the strain phylogeny. Selection of lineage-dependent specific associations of VAGs argues for strong epistatic interactions shaping the emergence of virulence inE. coli.

Background: Data on extended-spectrum β--lactamase-producing Escherichia coli (ESBL- E. coli) carriage in community settings, especially in developing countries, are scarce. Here, we describe the population structure and molecular characteristics of resistance of ESBL- E. coli faecal isolates in a rural African population.Methods: Between April and May 2017, stools of 383 healthy participants were collected from 20 villages in rural Southern Niger during a clinical trial on ciprofloxacin prophylaxis carried out during a meningococcal meningitis outbreak. Of 383 individuals, 354 (92.4%) were carriers of ESBL- E. coli before any ciprofloxacin intake. A subset of 90 of these ESBL- E. coli containing stools were selected for further analysis, from which 109 different ESBL- E. coli were recovered and whole genome sequenced by short-(Illumina) and long-(Nanopore) reads.FindingsMost belonged to the commensal-adapted phylogroup A (91, 83.5%), with high clonal diversity (57 distinct clones). One-quarter harboured the high pathogenicity island previously associated with a longer duration of faecal carriage.The bla CTX-M-15 gene was the major ESBL determinant (107, 98.1%). It was chromosome-integrated in approximately half of the cases (48, 44.9%), at multiple integration sites in diverse chromosomal genetic backgrounds. When plasmid-borne, blaCTX-M-15 was found in a large diversity of incompatibility groups. A single genetic background was found for 20 distinct plasmids, whereas very closely related plasmids were found in different genetic backgrounds in six cases, suggesting plasmid spread among strains. No geographical or social links to resistance patterns were observed.Interpretation: Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger without apparent antibiotic selective pressure. E. coli were highly diverse, well adapted commensal strains, with chromosomal integration of CTX-M-15 encoding gene in almost half of the cases. Evidence of clonal and plasmid spread suggest a risk of sustainable implementation in community faecal carriage.Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT02724046).Funding Information: This work was partially supported by a grant from the “Fondation pour la Recherche Médicale” (Equipe FRM 2016, grant number DEQ20161136698). The parent study was funded by Médecins Sans Frontières. Declaration of Interests: None.Ethics Approval Statement: The parent study protocol, which included this sub-study, was reviewed and approved by the National Consultative Ethics Committee of Niger (Ref: 003/2016/CCNE) and the Ethics Review Board of Médecins Sans Frontières (Ref: 1603). Written informed consent was obtained from individual participants.

Escherichia coli is an important cause of bloodstream infections (BSI), which is of concern given its high mortality and increasing worldwide prevalence. Finding bacterial genetic variants that might contribute to patient death is of interest to better understand infection progression and implement diagnostic methods that specifically look for those factors. E. coli samples isolated from patients with BSI are an ideal dataset to systematically search for those variants, as long as the influence of host factors such as comorbidities are taken into account. Here we performed a genome-wide association study (GWAS) using data from 912 patients with E. coli BSI from hospitals in Paris, France. We looked for associations between bacterial genetic variants and three patient outcomes (death at 28 days, septic shock and admission to intensive care unit), as well as two portals of entry (urinary and digestive tract), using various clinical variables from each patient to account for host factors. We did not find any association between genetic variants and patient outcomes, potentially confirming the strong influence of host factors in influencing the course of BSI; we however found a strong association between the papGII operon and entrance of E. coli through the urinary tract, which demonstrates the power of bacterial GWAS when applied to actual clinical data. Despite the lack of associations between E. coli genetic variants and patient outcomes, we estimate that increasing the sample size by one order of magnitude could lead to the discovery of some putative causal variants. Given the wide adoption of bacterial genome sequencing of clinical isolates, such sample sizes may be soon available.

SummaryObjectiveWhole genome sequencing (WGS) of extended-spectrum β-lactamase-producingEscherichia coli(ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. colifaecal isolates in rural Southern Niger.MethodsStools of 383 healthy participants were collected among which 92.4% were ESBL-E. colicarriers; 90 of these ESBL-E. colicontaining stools (109 ESBL-E. coliisolates) were further analysed by WGS, using short- and long-reads.ResultsMost isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. TheblaCTX-M-15gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne,blaCTX-M-15was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis ofblaCTX-M-15in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.ConclusionsMassive prevalence of community faecal carriage of CTX-M-15-producingE. coliwas observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration ofblaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.

To the Editor—We read with great interest the paper by Lipworth et al [1] published in the January 2021 issue of Clinical Infectious Diseases. O-antigen targeted vaccines against Escherichia coli may be useful in reducing morbidity, mortality, and antimicrobial resistance [2]. E. coli serotyping studies to guide vaccine target selection are limited. In their epidemiological report of more than 3000 E. coli strains responsible for bloodstream infections (BSIs) in Oxford, England, the authors found that the ExPEC4V and ExPEC10V vaccines under investigation would cover 45.7% and 72% of isolates, respectively [1]. However, as stated by the authors, the main limitation of their study is that it is from a single region and may therefore not be extrapolated to other regions of the world. We therefore would like to share our data from the Paris region in France. In 2 previous prospective...