Synergy between Group 2 capsules and lipopolysaccharide underpins serum resistance in extra-intestinal pathogenic Escherichia coli
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ABSTRACT:
SUBMITTER: McGarry N
PROVIDER: S-EPMC11342863 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Extra-intestinal pathogenic Escherichia coli (ExPEC) represent an emerging pathogen, with pandemic strains increasingly involved in cases of urinary tract infections (UTIs), bacteremia, and meningitis. In addition to affecting humans, the avian pathotype of ExPEC, avian pathogenic E. coli (APEC), causes severe economic losses to the poultry industry. Several studies have revealed overlapping characteristics between APEC and human ExPEC, leading to the hypothesis of a zoonotic potential of poultry strains. However, the description of certain important pandemic clones, such as Sequence Type 73 (ST73), has not been reported in food sources. We characterized 27 temporally matched APEC strains from diverse poultry farms in Brazil belonging to the O6 serogroup because this serogroup is frequently described as a causal factor in UTI and septicemia in humans in Brazil and worldwide. The isolates were genotypically characterized by identifying ExPEC virulence factors, phylogenetically tested by phylogrouping and multilocus sequence type (MLST) analysis, and compared to determine their similarity employing the pulsed field gel electrophoresis (PFGE) technique. The strains harbored a large number of virulence determinants that are commonly described in uropathogenic E. coli (UPEC) and sepsis associated E. coli (SEPEC) strains and, to a lesser extent in neonatal meningitis associated E. coli (NMEC), such as pap (85%), sfa (100%), usp (100%), cnf1 (22%), kpsMTII (66%), hlyA (52%), and ibeA (4%). These isolates also yielded a low prevalence of some genes that are frequently described in APEC, such as iss (37%), tsh, ompT, and hlyF (8% each), and cvi/cva (0%). All strains were classified as part of the B2 phylogroup and sequence type 73 (ST73), with a cluster of 25 strains showing a clonal profile by PFGE. These results further suggest the zoonotic potential of some APEC clonal lineages and their possible role in the epidemiology of human ExPEC, in addition to providing the first description of the O6-B2-ST73 clonal group in poultry.
| S-EPMC5464619 | biostudies-literature
Project description:In this study the transcriptional response of an ExPEC E. coli strain (CFT073) to human serum was investigated. In response, CFT073 up-regulated expression of iron and manganese acquisition systems and induced expression of iron regulated genes. High osmolarity of serum induced the osmotic shock response genes, promoting uptake of osmoprotectants by CFT073. Resistance of CFT073 to the bactericidal properties of serum involved increased expression of envelope stress regulators including CpxR, ?E and RcsB. Many of the up-regulated genes induced by active serum were regulated by the Rcs two component system. This system is triggered by envelope stress such as changes to cell wall integrity. RcsB-mediated serum resistance was conferred through induction of the exopolysaccharide colanic acid. Production of this exopolysaccharide may be protective while cell wall damage caused by serum components is repaired. Experimental Design: Two experiments are reported: 1) . The transcriptome of E. coli CFT073 exposed to LB supplemented with 50 % normal human serum was compared to that of bacteria grown in LB alone for 45 min, and 2) The transcriptome of CFT073 in response to normal healthy serum and heat inactivated serum (which has no bactericidal activity). Four biological replicates were performed per experiment with Dye swaps performed on sample replicates to eliminate any dye bias
2013-10-20 | E-MTAB-1985 | biostudies-arrayexpress
Project description:Extra-intestinal pathogenic Escherichia coli (ExPEC) strains cause many diseases in humans and animals. While remaining asymptomatic, they can colonize the intestine for subsequent extra-intestinal infection and dissemination in the environment. We have previously identified the fos locus, a gene cluster within a pathogenicity island of the avian ExPEC strain BEN2908, involved in the metabolism of short-chain fructooligosaccharides (scFOS). It is assumed that these sugars are metabolized by the probiotic bacteria of the microbiota present in the intestine, leading to a decrease in the pathogenic bacterial population. However, we have previously shown that scFOS metabolism helps BEN2908 to colonize the intestine, its reservoir. As the fos locus is located on a pathogenicity island, one aim of this study was to investigate a possible role of this locus in the virulence of the strain for chicken. We thus analysed fos gene expression in extracts of target organs of avian colibacillosis and performed a virulence assay in chickens. Moreover, in order to understand the involvement of the fos locus in intestinal colonization, we monitored the expression of fos genes and their implication in the growth ability of the strain in intestinal extracts of chicken. We also performed intestinal colonization assays in axenic and Specific Pathogen-Free (SPF) chickens. We demonstrated that the fos locus is not involved in the virulence of BEN2908 for chickens and is strongly involved in axenic chicken cecal colonization both in vitro and in vivo. However, even if the presence of a microbiota does not inhibit the growth advantage of BEN2908 in ceca in vitro, overall, growth of the strain is not favoured in the ceca of SPF chickens. These findings indicate that scFOS metabolism by an ExPEC strain can contribute to its fitness in ceca but this benefit is fully dependent on the bacteria present in the microbiota.
| S-EPMC3325963 | biostudies-literature
Project description:Extra-intestinal pathogenic Escherichia coli (ExPEC) ST1193, a globally emergent fluoroquinolone-resistant clone, has become an important cause of bloodstream infections (BSIs) associated with significant morbidity and mortality. Previous studies have reported the emergence of fluoroquinolone-resistant ExPEC ST1193 in Vietnam; however, limited data exist regarding the genetic structure, antimicrobial resistance (AMR) determinants and transmission dynamics of this pandemic clone. Here, we performed genomic and phylogenetic analyses of 46 ST1193 isolates obtained from BSIs and healthy individuals in Ho Chi Minh City, Vietnam, to investigate the pathogen population structure, molecular mechanisms of AMR and potential transmission patterns. We further examined the phylogenetic structure of ST1193 isolates in a global context. We found that the endemic E. coli ST1193 population was heterogeneous and highly dynamic, largely driven by multiple strain importations. Several well-supported phylogenetic clusters (C1-C6) were identified and associated with distinct blaCTX-M variants, including blaCTXM-27 (C1-C3, C5), blaCTXM-55 (C4) and blaCTXM-15 (C6). Most ST1193 isolates were multidrug-resistant and carried an extensive array of AMR genes. ST1193 isolates also exhibited the ability to acquire further resistance while circulating in Vietnam. There were phylogenetic links between ST1193 isolates from BSIs and healthy individuals, suggesting these organisms may both establish long-term colonization in the human intestinal tract and induce infections. Our study uncovers factors shaping the population structure and transmission dynamics of multidrug-resistant ST1193 in Vietnam, and highlights the urgent need for local One Health genomic surveillance to capture new emerging ExPEC clones and to better understand the origins and transmission patterns of these pathogens.
| S-EPMC8767341 | biostudies-literature
Project description:Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics.
| S-EPMC9236248 | biostudies-literature
Project description:Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some "zoonotic-related" STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.
| S-EPMC4130637 | biostudies-literature
Project description:Label-free quantitative proteomic analysis of Extra-intestinal Pathogenic Escherichia coli (ExPEC) Extracellular Vesicles (EVs)
2022-10-12 | PXD020207 |
Project description:Escherichia coli is a ubiquitous commensal and pathogen that has also been recognized as a multi-sectoral indicator of antimicrobial resistance (AMR). Given that latter focus, such as on resistances to extended-spectrum cephalosporins (ESC) and carbapenems, the reported population structure of E. coli is generally biased toward resistant isolates, with sequence type (ST)131 being widely reported in humans, and ST410 and ST648 being reported in animals. In this study, we characterized 618 non-duplicate E. coli isolates collected throughout France independently of their resistance phenotype. The B2 phylogroup was over-represented (79.6%) and positively associated with the presence of numerous virulence factors (VFs), including those defining the extra-intestinal pathogenic E. coli isolates (presence of ≥2 VFs: papA, sfaS, focG, afaD, iutA, and kpsMTII) and those more specifically related to uropathogenic E. coli (cnf1, hlyD). The major STs associated with clinical isolates from dogs were by far the dog-associated ST372 (20.7%) and ST73 (20.1%), a lineage that had commonly been considered until now as human-associated. Resistance to ESC was found in 33 isolates (5.3%), along with one carbapenemase-producing isolate, and was mostly restricted to non-B2 isolates. In conclusion, the presence of virulent E. coli lineages may be the issue, rather than the presence of ESC-resistant isolates, and the risk of transmission of such virulent isolates to humans needs to be further studied.
| S-EPMC7186358 | biostudies-literature
Project description:Extra-intestinal pathogenic Escherichia coli (ExPEC) are a significant cause of urinary tract infections and bacteraemia worldwide. Currently no single virulence factor or ExPEC lineage has been identified as the sole contributor to severe extra-intestinal infection and/or urosepsis. Galleria mellonella has recently been established as a simple model for studying the comparative virulence of ExPEC. In this study we investigated the virulence of 40 well-characterized ExPEC strains, in G. mellonella, by measuring mortality (larvae survival), immune recognition/response (melanin production) and cell damage (lactate dehydrogenase production). Although mortality was similar between urinary and bloodstream isolates, it was heightened for community-associated infections, complicated UTIs and urinary-source bacteraemia. Isolates of ST131 and those possessing afa/dra, ompT and serogroup O6 were also associated with heightened virulence.
| S-EPMC4601332 | biostudies-literature
Project description:It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.
| S-EPMC8739286 | biostudies-literature