Genome-Based Characterization of Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains Isolated in South Korea, 2016–2020

Lee, Woojung; Kim, Min-Hee; Sung, Soo-Hyun; Kim, Eiseul; An, Eun Sook; Kim, Seunghwan; Kim, Soon Han; Kim, Hae Yeong

doi:10.3390/microorganisms11051285

Cited by 12 publications

(5 citation statements)

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“…STEC and ETEC are significant contributors to diarrhea in both humans and animals globally. Recent reports from diverse geographical regions, including Finland, Bangladesh, Sweden, and South Korea, have revealed the existence of hybrids resulting from the combination of STEC and ETEC strains, categorized as STEC/ETEC hybrids ( 7 , 8 , 52 – 54 ). Genome-wide phylogenetic analyses have shown a strong association between these hybrids and specific strains of ETEC and STEC, suggesting potential acquisition of Stx-phage and/or ETEC virulence genes during the evolution of STEC/ETEC hybrids ( 1 , 10 – 12 ).…”

Section: Discussionmentioning

confidence: 99%

ArcA positively regulates the expression of virulence genes and contributes to virulence of porcine Shiga toxin-producing enterotoxigenic Escherichia coli

Jiang,

Yang,

Mao

et al. 2023

Microbiol Spectr

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Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhea in humans and animals. These bacteria encode two major classes of virulence factors, adhesins that promote colonization of the small intestine and enterotoxins that induce fluid secretion and thus diarrhea. Oxygen and redox sensors are regulators of virulence expression in multiple bacterial pathogens. In this study, we show that microaerobic conditions enhance the expression of virulence factors in a porcine Shiga toxin-producing ETEC (STEC/ETEC) strain. We then investigated the role of the aerobic respiration control regulator ArcA in the pathogenicity and virulence regulation in STEC/ETEC. In a mouse model, deletion of arcA caused less severe pathology, and the arcA mutant displayed lower levels of colonization and obvious weight gain of the mice compared to the wild type (WT). In a cell culture model, a lack of arcA reduced the adherence of STEC/ETEC to porcine intestinal epithelial cells. Furthermore, ArcA positively regulated the expression of several key virulence factors, including F18 fimbriae ( fed ), heat-labile ( eltA ) and heat-stable ( estB ) toxins, Shiga toxin 2e ( stx2e ), and hemolysin ( hlyC ), under microaerobic conditions and in vivo conditions. We then found that ArcA positively regulated the expression of eltA , estB , and hlyC by competing with a global repressor H-NS (histone-like nucleoid structuring). Mechanistically, we show that ArcA protein directly binds to the promoters of target genes, displaces H-NS silencing from the promoter and counteracts H-NS’s repression. Collectively, our data established a key role for ArcA in the pathogenicity and virulence expression of porcine STEC/ETEC. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhea in humans and animals, leading to death and huge economic loss worldwide. Thus, elucidation of ETEC’s pathogenic mechanisms will provide powerful data for the discovery of drugs serving as prevention or therapeutics against ETEC-caused diarrheal diseases. Here, we report that ArcA plays an essential role in the pathogenicity and virulence regulation in ETEC by positively regulating the expression of several key virulence factors including F18 fimbriae, heat-labile and heat-stable toxins, Shiga toxin 2e, and hemolysin, under microaerobic conditions and in vivo . Moreover, we found that positive regulation of several virulence genes by ArcA requires a global repressor H-NS (histone-like nucleoid structuring), implying that ArcA may exert positive effects by antagonizing H-NS. Collectively, our data established a key role for ArcA in the pathogenicity of porcine ETEC and ETEC strains isolated from human infections. Moreover, our work reveals another layer of regulation in relation to oxygen control of virulence factors in ETEC.

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Section: Discussionmentioning

confidence: 99%

ArcA positively regulates the expression of virulence genes and contributes to virulence of porcine Shiga toxin-producing enterotoxigenic Escherichia coli

Jiang,

Yang,

Mao

et al. 2023

Microbiol Spectr

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“…Real-time PCR was performed using a PowerCheckTM 20/15 Pathogen Multiplex Real-time PCR kit (Kogen Biotech Co., Ltd., Seoul, Republic of Korea) to detect virulence genes in different DEC pathogens, including VT1 and VT2 (STEC); bfpA and eaeA (EPEC); LT , STh and STp (ETEC); aggR (EAEC); ipaH (EIEC) ( Lee et al, 2023a , b ).…”

Section: Methodsmentioning

confidence: 99%

“…We conducted a comparative genomic analysis of 32 hybrid STEC/aEPEC strains isolated in South Korea and 187 other pathogenic E. coli strains ( Lee et al, 2023a , b ). To analyze the pan-genome, we used the bacterial pan-genome analysis (BPGA) tool (v1.3) with default parameters.…”

Section: Methodsmentioning

confidence: 99%

“…Diarrheal disease outbreaks associated with various DEC pathotypes occurred in Germany in 2011 ( Buchholz et al, 2011 ), Japan in 2016 ( Furukawa et al, 2018 ) and 2020 ( Kashima et al, 2021 ), Nottingham, UK in 2014 ( Newitt et al, 2016 ), South Korea in 2018 ( Lim et al, 2020 ), and the United Kingdom in 2020 ( Mulchandani et al, 2021 ). Hybrid strains are characterized by the presence of virulence genes unique to multiple E. coli pathotypes, typically detected via PCR or comprehensive whole-genome sequencing (WGS) ( Jesser and Levy, 2020 ; Lee et al, 2023a , b ). Cell-based assays have also been used to assess the virulence potential of hybrid strains ( Valiatti et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Genetic and virulence characteristics of hybrid Shiga toxin-producing and atypical enteropathogenic Escherichia coli strains isolated in South Korea

Lee,

Ha,

Choi

et al. 2024

Front. Microbiol.

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IntroductionThe predominant hybrid pathogenic E. coli, enterohemorrhagic E. coli (EHEC), combines characteristics of Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC), contributing to global outbreaks with severe symptoms including fatal consequences. Since EHEC infection was designated as a notifiable disease in 2000 in South Korea, around 2000 cases have been reported, averaging approximately 90 cases annually.AimIn this work, genome-based characteristic analysis and cell-based assay of hybrid STEC/aEPEC strains isolated from livestock feces, animal source foods, and water in South Korea was performed.MethodsTo identify the virulence and antimicrobial resistance genes, determining the phylogenetic position of hybrid STEC/aEPEC strains isolated in South Korea, a combination of real-time PCR and whole-genome sequencing (WGS) was used. Additionally, to assess the virulence of the hybrid strains and compare them with genomic characterization, we performed a cell cytotoxicity and invasion assays.ResultsThe hybrid STEC/aEPEC strains harbored stx and eae genes, encoding Shiga toxins and E. coli attachment/effacement related protein of STEC and EPEC, respectively. Furthermore, all hybrid strains harbored plasmid-carried enterohemolysin(ehxCABD), a key virulence factor in prevalent pathogenic E. coli infections, such as diarrheal disease and hemolytic-uremic syndrome (HUS). Genome-wide phylogenetic analysis revealed a close association between all hybrid strains and specific EPEC strains, suggesting the potential acquisition of Stx phages during STEC/aEPEC hybrid formation. Some hybrid strains showed cytotoxic activity against HeLa cells and invasive properties against epithelial cells. Notably, all STEC/aEPEC hybrids with sequence type (ST) 1,034 (n = 11) exhibited higher invasiveness than those with E2348/69. This highlights the importance of investigating potential correlations between STs and virulence characteristics of E. coli hybrid strains.ConclusionThrough genome-based characterization, we confirmed that the hybrid STEC/aEPEC strains are likely EPEC strains that have acquired STEC virulence genes via phage. Furthermore, our results emphasize the potential increased danger to humans posed by hybrid STEC/aEPEC strains isolated in South Korea, containing both stx and eaeA, compared to STEC or EPEC alone.

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“…Shiga toxin-producing Escherichia coli (STEC) strains are globally recognized as significant causes of diarrhea in both humans and animals ( Lee et al, 2023 ). These strains are known for their ability to produce one or two distinct types of Shiga toxin (Stx), which serve as the primary virulence factor.…”

Section: Introductionmentioning

confidence: 99%

Genomic traits of multidrug resistant enterotoxigenic Escherichia coli isolates from diarrheic pigs

Jiang-hong

Huang

et al. 2023

Front. Microbiol.

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Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) infections poses a significant challenge in global pig farming. To address this issue, the study was conducted to identify and characterize 19 ETEC isolates from fecal samples of diarrheic pigs sourced from large-scale farms in Sichuan Province, China. Whole-genome sequencing and bioinformatic analysis were utilized for identification and characterization. The isolates exhibited substantial resistance to cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, gentamicin, ampicillin, tetracycline, florfenicol, and sulfadiazine, but were highly susceptible to amikacin, imipenem, and cefoxitin. Genetic diversity among the isolates was observed, with serotypes O22:H10, O163orOX21:H4, and O105:H8 being dominant. Further analysis revealed 53 resistance genes and 13 categories of 195 virulence factors. Of concern was the presence of tet(X4) in some isolates, indicating potential public health risks. The ETEC isolates demonstrated the ability to produce either heat-stable enterotoxin (ST) alone or both heat-labile enterotoxin (LT) and ST simultaneously, involving various virulence genes. Notably, STa were linked to human disease. Additionally, the presence of 4 hybrid ETEC/STEC isolates harboring Shiga-like toxin-related virulence factors, namely stx2a, stx2b, and stx2e-ONT-2771, was identified. IncF plasmids carrying multiple antimicrobial resistance genes were prevalent, and a hybrid ETEC/STEC plasmid was detected, highlighting the role of plasmids in hybrid pathotype emergence. These findings emphasized the multidrug resistance and pathogenicity of porcine-origin ETEC strains and the potential risk of epidemics through horizontal transmission of drug resistance, which is crucial for effective control strategies and interventions to mitigate the impact on animal and human health.

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Genome-Based Characterization of Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains Isolated in South Korea, 2016–2020

Cited by 12 publications

References 56 publications

ArcA positively regulates the expression of virulence genes and contributes to virulence of porcine Shiga toxin-producing enterotoxigenic Escherichia coli

ArcA positively regulates the expression of virulence genes and contributes to virulence of porcine Shiga toxin-producing enterotoxigenic Escherichia coli

Genetic and virulence characteristics of hybrid Shiga toxin-producing and atypical enteropathogenic Escherichia coli strains isolated in South Korea

Genomic traits of multidrug resistant enterotoxigenic Escherichia coli isolates from diarrheic pigs

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