Genomic evolution of antimicrobial resistance in Escherichia coli.
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ABSTRACT:
SUBMITTER: Leekitcharoenphon P
PROVIDER: S-EPMC8302606 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:aEPEC are associated with persistent diarrhea, and diarrheal outbreaks in both humans and animals worldwide. They are differentiated from typical EPEC by the lack of bundle-forming pili, and from EHEC by the lack of phage-mediated stx toxins. However, phylogenetic analyses often associate aEPEC with EHEC, promoting the hypothesis that aEPEC are the progenitors of EHEC, which is supported by aEPEC conversion to EHEC by stx-carrying phages. While aEPEC can cause disease outright, the potential to acquire stx, one of the most potent bacterial toxins known, merits close monitoring. Escherichia coli ST302 (O108:H9, O182:H9, O45:H9) are aEPEC that have been isolated from diarrheic human, pig and rabbit hosts, as well as in healthy pigs, however, no study to date has focused on E. coli ST302 strains. Through WGS and hybrid assembly we present the first closed chromosome, and two circularized plasmids of an ST302 strain - F2_18C, isolated from a healthy pig in Australia. A phylogenetic analysis placed E. coli ST302 strains in proximity to EHEC ST32 (O145:H28) strains. Public databases were interrogated for WGSs of E. coli ST302 strains and short-read gene screens were used to compare their virulence-associated gene (VAG) and antimicrobial resistance gene (ARG) cargo. E. coli ST302 strains carry diverse VAGs, including those that typically associated with extraintestinal pathogenic E. coli (ExPEC). Plasmid comparisons showed that pF2_18C_FIB shared homology with EHEC virulence plasmids such as pO103 while pF2_18C_HI2 is a large multidrug resistance IncHI2:ST3 plasmid. A comparison of 33 HI2:ST3 plasmids demonstrated that those of Australian origin have not acquired resistances to extended-spectrum beta-lactams, colistin, fosfomycin or rifampicin, unlike those originating from Asia. F2_18C was shown to carry two additional pathogenicity islands - ETT2, and the STEC-associated PAI CL 3, plasmid-associated heavy metal resistance genes, as well as several unoccupied stx-phage attachment sites. This study sheds light on the virulence and AMR potential of E. coli ST302 strains and informs AMR genomic surveillance.
| S-EPMC6985150 | biostudies-literature
Project description:BackgroundEscherichia coli is a leading cause of bloodstream infections. Developing interventions to reduce E coli infections requires an understanding of the frequency of nosocomial transmission, but the available evidence is scarce. We aimed to detect and characterise transmission of E coli and associated plasmids in a hospital setting.MethodsIn this prospective observational cohort study, patients were admitted to two adult haematology wards at the Cambridge University Hospitals NHS Foundation Trust in England. Patients aged 16 years and older who were treated for haematological malignancies were included. Stool samples were collected from study participants on admission, once per week, and at discharge. We sequenced multiple E coli isolates (both extended spectrum β-lactamase [ESBL]-producing and non-ESBL-producing) from each stool sample. A genetic threshold to infer E coli transmission was defined by maximum within-host single nucleotide polymorphism (SNP) diversity and the probability of drawing observed pairs of between-patient isolates at different SNP thresholds. Putative transmission clusters were identified when sequences were less than the genetic threshold. Epidemiological links for each transmission event were investigated. We sequenced all E coli positive blood samples from the two adult haematology wards.FindingsWe recruited 174 (51%) of 338 adult patients admitted to the wards between May 13 and Nov 13, 2015. We obtained and cultured 376 stool samples from 149 patients, of which 152 samples from 97 (65%) patients grew E coli. Whole-genome sequencing was done on 970 isolates. We identified extensive diversity in the bacterial population (90 sequence types) and mixed E coli sequence type carriage. 24 (26%) patients carried two sequence types, 12 (13%) carried three, and six (6%) patients carried four or more sequence types. Using a 17 SNP cutoff we identified ten clusters in 20 patients. The largest cluster contained seven patients, whereas four patients were included in multiple clusters. Strong epidemiological links were found between patients in seven clusters. 17 (11%) of 149 patients had stool samples positive for ESBL-producing E coli, the most common of which was associated with bla CTX-M-15 (12 [71%] of 17). Long-read sequencing revealed that bla CTX-M-15 was often integrated into the chromosome, with little evidence for plasmid transmission. Seven patients developed E coli bloodstream infection, four with identical strains to those in their stool; two of these had documented nosocomial acquisition.InterpretationWe provide evidence of bacterial transmission and endogenous infection during routine care by integrating genomic and epidemiological data and by determining a genetic cutoff informed by within-host diversity in the studied population. Our findings challenge single colony-based investigations, and the widely accepted notion of plasmid spread.FundingUK Department of Health, Wellcome Trust, UK National Institute for Health Research.
| S-EPMC8410606 | biostudies-literature
Project description:To combat antimicrobial resistance (AMR), policymakers need an overview of evolution and trends of AMR in relevant animal reservoirs, and livestock is monitored by susceptibility testing of sentinel organisms such as commensal E. coli. Such monitoring data are often vast and complex and generates a need for outcome indicators that summarize AMR for multiple antimicrobial classes. Model-based clustering is a data-driven approach that can help to objectively summarize AMR in animal reservoirs. In this study, a model-based cluster analysis was carried out on a dataset of minimum inhibitory concentrations (MIC), recoded to binary variables, for 10 antimicrobials of commensal E. coli isolates (N = 12,986) derived from four animal species (broilers, pigs, veal calves and dairy cows) in Dutch AMR monitoring, 2007-2018. This analysis revealed four clusters in commensal E. coli in livestock containing 201 unique resistance combinations. The prevalence of these combinations and clusters differs between animal species. Our results indicate that to monitor different animal populations, more than one indicator for multidrug resistance seems necessary. We show how these clusters summarize multidrug resistance and have potential as monitoring outcome indicators to benchmark and prioritize AMR problems in livestock.
| S-EPMC8048968 | biostudies-literature
Project description:Background and Objectives:Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties. Methodology:Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance. Results:By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC ?/? yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ?; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD ?/? entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF ?/? yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance. Conclusions:This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to an atom that mimics an essential micronutrient and shows the pleiotropic consequences associated with this adaptation. Lay summary:We utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance.
| S-EPMC6928379 | biostudies-literature
Project description:Escherichia coli (E. coli) are typically present as commensal bacteria in the gastro-intestinal tract of most animals including poultry species, but some avian pathogenic E. coli (APEC) strains can cause localized and even systematic infections in domestic poultry. Emergence and re-emergence of antimicrobial resistant isolates (AMR) constrain antibiotics usage in poultry production, and development of an effective vaccination program remains one of the primary options in E. coli disease prevention and control for domestic poultry. Thus, understanding genetic and pathogenic diversity of the enzootic E. coli isolates, particularly APEC, in poultry farms is the key to designing an optimal vaccine candidate and to developing an effective vaccination program. This study explored the genomic and pathogenic diversity among E. coli isolates in southern United States poultry. A total of nine isolates were recovered from sick broilers from Mississippi, and one from Georgia, with epidemiological variations among clinical signs, type of housing, and bird age. The genomes of these isolates were sequenced by using both Illumina short-reads and Oxford Nanopore long-reads, and our comparative analyses suggested data from both platforms were highly consistent. The 16 s rRNA based phylogenetic analyses showed that the 10 bacteria strains are genetically closer to each other than those in the public database. However, whole genome analyses showed that these 10 isolates encoded a diverse set of reported virulence and AMR genes, belonging to at least nine O:H serotypes, and are genetically clustered with at least five different groups of E. coli isolates reported by other states in the United States. Despite the small sample size, this study suggested that there was a large extent of genomic and serological diversity among E. coli isolates in southern United States poultry. A large-scale comprehensive study is needed to understand the overall genomic diversity and the associated virulence, and such a study will be important to develop a broadly protective E. coli vaccine.
| S-EPMC9841705 | biostudies-literature
Project description:Extended-Spectrum-Cephalosporin (ESC)-resistant Enterobacteriaceae have widely spread in all settings worldwide. In animals, Extended-Spectrum Beta-Lactamase (ESBL) producers have been frequently identified in veal calves. The objectives of this study were to investigate the trends in the ESBL load and antimicrobial resistance (AMR) proportions, and antimicrobial usages (AMU) in veal calves during the fattening process. Ten fattening farms were selected and 50 animals per farm were sampled. AMR was assessed in bacteria from the dominant flora (collected on non-selective MacConckey agar) and in ESBL/AmpC-carrying bacteria from the subdominant flora (selected on ChromID ESBL selective plates) upon arrival and 5-6 months later before slaughter. The number and types of treatments during fattening were also collected. Rates of ESBL-producing E. coli from the subdominant flora significantly decreased in all farms (arrival: 67.7%; departure: 20.4%) whereas rates of multidrug-resistant E. coli from the dominant flora have significantly increased (arrival: 60.2%; departure: 67.2%; p = 0.025). CTX-M-1 was the most frequently identified ESBL enzyme (arrival: 59.3%; departure: 52.0%). The plasmid-mediated mcr-1 gene was also identified occasionally. In parallel, levels of resistances to non-critically important antimicrobials were already high upon arrival but have still further increased over time until slaughter. Our study also highlighted that if only ESBL-producing isolates were monitored, it might have led to a partial (and partly false) picture of AMR rates globally decreasing during the fattening period. The mean number of antimicrobial treatments per calf (NTPC) was 8.75 but no association between AMU and AMR was evidenced. Most ESBL producers were clonally unrelated suggesting multiple sources and not cross-contaminations among calves during transportation. Feeding milk containing antimicrobial residues to veal calves is hypothesized to explain the high ESBL loads in animals at the entrance on farms.
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Project description:Escherichia coli is the most common cause of human and canine urinary tract infection (UTI). Clonal groups, often with high levels of antimicrobial resistance, are a major component of the E. coli population that causes human UTI. While little is known about the population structure of E. coli that causes UTI in dogs, there is evidence that dogs and humans can share fecal strains of E. coli and that human-associated strains can cause disease in dogs. In order to better characterize the E. coli strains that cause canine UTI, we analyzed 295 E. coli isolates obtained from canine urine samples from five veterinary diagnostic laboratories and analyzed their multilocus sequence types, phenotypic and genotypic antimicrobial resistance profiles, and virulence-associated gene repertoires. Sequence type 372 (ST372), an infrequent human pathogen, was the predominant sequence type in dogs at all locations. Extended-spectrum β-lactamase-producing isolates with blaCTX-M genes were uncommon in canine isolates but when present were often associated with sequence types that have been described in human infections. This provides support for occasional cross-host-species sharing of strains that cause extraintestinal disease and highlights the importance of understanding the role of companion animals in the overall transmission patterns of extraintestinal pathogenic E. coli.
| S-EPMC6113483 | biostudies-literature
Project description:We have generated extreme ionizing radiation resistance in a relatively sensitive bacterial species, Escherichia coli, by directed evolution. Four populations of Escherichia coli K-12 were derived independently from strain MG1655, with each specifically adapted to survive exposure to high doses of ionizing radiation. D(37) values for strains isolated from two of the populations approached that exhibited by Deinococcus radiodurans. Complete genomic sequencing was carried out on nine purified strains derived from these populations. Clear mutational patterns were observed that both pointed to key underlying mechanisms and guided further characterization of the strains. In these evolved populations, passive genomic protection is not in evidence. Instead, enhanced recombinational DNA repair makes a prominent but probably not exclusive contribution to genome reconstitution. Multiple genes, multiple alleles of some genes, multiple mechanisms, and multiple evolutionary pathways all play a role in the evolutionary acquisition of extreme radiation resistance. Several mutations in the recA gene and a deletion of the e14 prophage both demonstrably contribute to and partially explain the new phenotype. Mutations in additional components of the bacterial recombinational repair system and the replication restart primosome are also prominent, as are mutations in genes involved in cell division, protein turnover, and glutamate transport. At least some evolutionary pathways to extreme radiation resistance are constrained by the temporally ordered appearance of specific alleles.
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Project description:The recent exponential increase in the use of engineered nanoparticles (eNPs) means both greater intentional and unintentional exposure of eNPs to microbes. Intentional use includes the use of eNPs as biocides. Unintentional exposure results from the fact that eNPs are included in a variety of commercial products (paints, sunscreens, cosmetics). Many of these eNPs are composed of heavy metals or metal oxides such as silver, gold, zinc, titanium dioxide, and zinc oxide. It is thought that since metallic/metallic oxide NPs impact so many aspects of bacterial physiology that it will difficult for bacteria to evolve resistance to them. This study utilized laboratory experimental evolution to evolve silver nanoparticle (AgNP) resistance in the bacterium Escherichia coli (K-12 MG1655), a bacterium that does not harbor any known silver resistance elements. After 225 generations of exposure to the AgNP environment, the treatment populations demonstrated greater fitness vs. control strains as measured by optical density (OD) and colony forming units (CFU) in the presence of varying concentrations of 10 nm citrate-coated silver nanoparticles (AgNP) or silver nitrate (AgNO3). Genomic analysis shows that changes associated with AgNP resistance were already accumulating within the treatment populations by generation 100, and by generation 200 three mutations had swept to high frequency in the AgNP resistance stocks. This study indicates that despite previous claims to the contrary bacteria can easily evolve resistance to AgNPs, and this occurs by relatively simple genomic changes. These results indicate that care should be taken with regards to the use of eNPs as biocides as well as with regards to unintentional exposure of microbial communities to eNPs in waste products.
| S-EPMC4330922 | biostudies-literature
Project description:The adherent invasive Escherichia coli (AIEC) pathotype has been associated with the aetiology of Crohn's disease (CD). Scarce reports have shown the antimicrobial resistance (AMR) profiles of AIEC. Despite antibiotics not being recommended to treat CD, antimicrobial therapy could be useful in stratified patients, such as AIEC carriers. We examined the antimicrobial resistance profiles of AIEC strains to identify which therapies could be effective or confer a risk for such patients. Phenotypic resistance to 30 antimicrobials was tested according to CLSI standards. AIEC (n = 22) and non-pathogenic E. coli (non-AIEC) strains (n = 37) isolated from the gut mucosa of 31 CD patients and 18 controls were studied. De novo genome sequencing was carried out for 39 of the 59 strains, and AMR genes were searched using the DeepARG database in these genomes and 33 additional AIEC publicly available genomes. The strains isolated from CD and controls showed similar phenotypic AMR profiles. The genomic analysis did not reveal an increased prevalence of AMR genes. However, AIEC strains were more frequently resistant to ?-lactams than non-AIEC strains (11 AIEC (50%) and 5 non-AIEC (22%) strains were resistant to at least one ?-lactam; p < 0.042). Two AIEC strains were resistant to expanded-spectrum cephalosporins. One strain carried a plasmid-mediated AmpC ?-lactamase (CMY-69), and the other presented mutations in the promotor of the intrinsic chromosomal AmpC related to the hyperproduction of this enzyme. The rest of the strains were resistant to ?-lactams not including expanded-spectrum cephalosporins. The majority carried TEM-related ?-lactamases. Genomic analysis including external AIEC revealed that the gene sul1 encoding for sulphonamide resistance was more frequent in AIEC strains than non-AIEC strains (34.6% vs. 9.5%, p = 0.030). AMR in AIEC is a matter of concern regarding the putative implication of the pathotype in CD. The high proportion of AIEC resistant to ?-lactams warrants caution about the risk there may be in the use of these antimicrobials in AIEC-colonized CD patients.
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