Open access peer-reviewed chapter - ONLINE FIRST

Dual Nature of Escherichia coli: Useful Biological Tool versus Notorious Pathogen

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Hui Chen, Yaqi Zhao, Zixuan Yan, Tianran Zhao, Yuge Liu, Lanxi Zhang and Ping Zeng

Submitted: 28 April 2025 Reviewed: 28 July 2025 Published: 25 August 2025

DOI: 10.5772/intechopen.1012282

<em>Escherichia coli</em> - From Normal Intestinal Bacteria to Lethal Microbes IntechOpen
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Abstract

This introductory chapter provides a comprehensive overview of Escherichia coli (E. coli), highlighting its dual nature as both a nonpathogenic and pathogenic microorganism. Nonpathogenic strains are crucial components of the intestinal microbiota. Moreover, as a model species in modern biology, E. coli plays a central role in diverse biomedical fields, such as genetic and molecular research, recombinant protein expression, and metabolic engineering. In addition to its significance in the health sector, E. coli possesses substantial biotechnological potential, with diverse applications spanning industrial synthesis, energy production, and environmental remediation, including power generation and wastewater treatment. On the contrary, by investigating the epidemiological and clinical implications of pathogenic strains, this chapter also underscores the significant public health threat posed by these strains and highlights the urgent need to develop innovative therapeutic strategies to combat resistance mechanisms, including drug-resistant plasmids. Overall, this chapter elucidates the dual nature of E. coli and underscores its significance in advancing our understanding of bacteriology, as well as in tackling global health and sustainability challenges.

Keywords

  • intestinal flora
  • nonpathogenic strain
  • pathogenic microorganism
  • drug resistance
  • novel therapeutics

1. Introduction

E. coli is an important model organism in modern biology, offering a range of advantages and widespread applications [1]. As a gram-negative bacterium, E. coli has a simple cellular structure and a rapid reproduction rate. Its small genome, which been completely sequenced and annotated, facilitates genetic and physiological research [2]. E. coli is widely used in the study of gene expression regulation, translation processes, protein folding and modification, and can also help in the study of microbial metabolic pathways and their regulation [3]. E. coli is a commonly used host bacterium, capable of introducing foreign genes to produce therapeutic proteins or industrial enzymes [4]. The composition of the culture medium for E. coli is simple and inexpensive, and the culture and experimental techniques are easy to master, with high safety of the experimental strains. With these advantages, E. coli is indispensable in various fields of modern biology and has effectively promoted the progress of life sciences [5].

E. coli has a dual nature, including nonpathogenic and pathogenic aspects. Nonpathogenic strains are members of normal flora of the human and animal intestines, which can maintain the balance of intestinal microecology, participate in the digestion and absorption of food, and synthesize vitamins [6]. For instance, vitamin K and some B vitamins produced by E. coli are essential for normal physiological functions. Vitamin K participates in the blood coagulation process, and B vitamins play an important role in energy metabolism and nervous system function. Furthermore, nonpathogenic strains enhance intestinal immune function, thus preventing pathogenic bacteria from colonization [7].

E. coli is a commonly host bacterium in genetic engineering and is a gene engineering vector. Its genome is relatively small, which would be easy to perform genetic manipulations and introduce foreign genes into E. coli, facilitating the expression of required proteins, such as insulin, growth hormone, interferon, and other biopharmaceuticals [8]. Moreover, E. coli cells are able to synthesize target proteins quickly in large quantities. By optimizing expression system, it can achieve the expression of different types of proteins, providing strong support for structure and function research and vaccine development [9]. These could provide important means for the treatment of diseases.

Since E. coli exists in large quantities in the intestines of humans and animals and has a relatively short survival time in the environment, it is often used as an indicator bacterium for fecal contamination of water bodies and soil. By detecting the number of E. coli in environmental samples, we can indirectly analyze whether the environment has been contaminated by feces and the extent of pollution, thereby providing a basis for environmental quality monitoring and public health protection [10].

On the contrary, pathogenic strains have special virulence factors, such as producing toxins or having structures such as flagella, which can help them colonize, reproduce, and cause disease in the host body [11]. Pathogenic strains can be divided into enterohaemorrhagic, enteropathogenic, enteroinvasive, and other types, leading to various diseases. In severe cases, it can result in dehydration, electrolyte disturbances, and even life-threatening conditions [12]. Additionally, pathogenic E. coli strains can also cause extraintestinal infections, such as urinary tract, sepsis, meningitis, especially in people with weakened immune systems [13].

In summary, E. coli plays a crucial role in modern biological research. The study of E. coli has been instrumental in elucidating fundamental principles of bacterial physiology and gene regulation. For instance, E. coli research has provided a framework for understanding bacterial gene regulation through operons, allostery, and environmental sensing, while also shedding light on physiological adaptations in metabolism, stress response, and host interactions. With the continuous deepening of future life science research, the functions of E. coli will be further explored through synthetic biology and multi-omics technologies. For example, engineered metabolic pathways allow E. coli to produce non-native high-value compounds, and comparative multi-omics quantifies strain-specific variations to match phenotypes with industrial needs.

The application prospects of E. coli in various fields will be broader, and the research and utilization of E. coli will continue to promote the development of human health and biotechnology industries, bringing more innovation to medical treatment, green manufacturing, and other fields.

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2. Nonpathogenic E. coli: Biology and applications

2.1 Role in gut microbiota and gastrointestinal colonization

E. coli is widely distributed in the intestinal tracts of humans and animals and can be classified into pathogenic and nonpathogenic strains based on its virulence. Nonpathogenic E. coli was once overlooked, but in recent years, it has emerged as a research hot spot due to its critical functions and potential in multiple fields [14]. In-depth exploration of nonpathogenic E. coli contributes to a better understanding of gut microbiota ecology, genetic and molecular mechanisms, and the development of industrial applications.

The gut microbiota is a complex microbial community that symbiotically inhabits the human intestinal tract and plays a crucial role in host health. As a key component of the normal microbiota, nonpathogenic E. coli helps suppress harmful microorganisms and maintains the dominance of beneficial bacteria [15]. Adhesion factors, like fimbriae on the bacterial surface, could facilitate its attachment to intestinal epithelial cells, thus enabling colonization. Once established, it forms a biological barrier against pathogen invasion while its metabolic activities stimulate intestinal epithelial development and enhance mucosal immunity [16]. Studies indicated that nonpathogenic E. coli can induce epithelial cells to secrete antimicrobial peptides and cytokines, thereby strengthening immune defenses [17].

2.2 Applications as a model organism

Due to diverse growth phenotypes and adaptability of E. coli, it serves as an ideal biological model for studying responses to varying growth conditions and ecological niches. The genome of nonpathogenic E. coli is compact with well-characterized regulatory mechanisms, facilitating genetic manipulation. Its simple culture requirements, rapid reproduction (doubling time ~ 20 minutes), and well-established genetic tools, like gene knockout systems, make it a powerful platform for functional genomics research [18].

As a widely used host for recombinant protein production, engineered E. coli can efficiently synthesize biopharmaceuticals such as insulin. Strategies including codon optimization and chaperone co-expression enhance protein yield and solubility [19]. Additionally, genetic editing redirects metabolic fluxes to synthesize high-value compounds like biodiesel from fatty acid metabolism and food-grade amino acids [20]. As a biocatalyst, E. coli enables sustainable synthesis of natural products under mild conditions, reducing reliance on hazardous chemical processes.

In medical application, genetically engineered E. coli is designed for targeted delivery of anticancer drugs. Such kind of “bacterial robot” can accurately gather in the tumor hypoxia area to release therapeutic agents [21]. There are also studies that use E. coli as a living diagnosis system to generate color signals by sensing specific metabolic markers, so as to realize early non-invasive diagnosis of diseases [22].

Recently, an engineered probiotic E. coli was reported to deliver an αPD-L1-PE38 fusion toxin directly to tumors [23]. Another work designed an E. coli-quantum dots biohybrid system for direct converting glycerol to H2 production with a high rate [24]. These advancements demonstrate the wide-ranging application of E. coli in various fields.

2.3 Industrial applications

Industrially, engineered E. coli produces diverse compounds, such as human milk oligosaccharides including 2′-fucosyllactose, 3′-sialyllactose, and 6′-sialyllactose, with scalable and automatable fermentation processes [25]. Under anaerobic conditions, E. coli oxidizes organic matter to generate electrons and protons, producing electric current. Optimizing strains and reactor designs improves power output [26]. In the field of biohydrogen production, genetic modifications enhance hydrogen yield and substrate utilization efficiency, supporting scalable clean energy generation [27].

E. coli can be also applied to environmental remediation, including degrading organic pollutants in wastewater by reducing the ratio of chemical oxygen demand and biochemical oxygen demand (COD/BOD) and absorbing nitrogen and phosphorus to mitigate eutrophication. In addition, for soil remediation, modulating microbial communities to degrade organic pollutants and immobilizing heavy metals by E. coli will be beneficial for improving fertility and structure. Engineered strains show improved degradation of recalcitrant contaminants [28].

Collectively, nonpathogenic E. coli holds immense value in gut ecology, molecular research, and industrial biotechnology. However, challenges such as unclear microbial interactions in the gut and suboptimal production efficiency in industrial settings remain unsolved. Future research should integrate advanced technologies like multi-omics and synthetic biology to expand its applications, offering solutions for health, energy, and environmental sustainability.

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3. Pathogenic E. coli: Prevalence and challenges

3.1 Overview of important strains

Pathogenic E. coli is capable of causing various diseases in humans and animals. Certain pathogenic strains carrying specific virulence factors may cause intestinal or extraintestinal infections through different mechanisms [29]. Based on their pathogenic mechanisms, clinical manifestations, and epidemiological characteristics, pathogenic E. coli in the gut can be primarily categorized into six types: enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enterohemorrhagic E. coli (EHEC), enteroaggregative E. coli (EAEC), and diffuse adherent E. coli (DAEC). Extraintestinal infections are mainly caused by uropathogenic E. coli (UPEC) and neonatal meningitis-causing E. coli (NMEC) [30]. These pathogens spread through contaminated water sources, food, or human-to-human contact, causing mild diarrhea to severe complications such as hemolytic uremic syndrome (HUS). In recent years, the emergence of drug-resistant pathogenic E. coli has further exacerbated public health challenges. This section will systematically explore the virulence factors, pathogenic mechanisms, epidemiological characteristics, and clinical challenges of three most iconic pathogenic E. coli strains, EHEC, ETEC, and UPEC.

3.1.1 EHEC

EHEC is a type of pathogenic E. coli that produces Shiga toxin (Stx), primarily causing hemorrhagic colitis and HUS. The most representative serotype is O157:H7, which has been the most common serotype responsible for human disease both domestically and internationally in recent years [31]. However, other serotypes such as O26:H11, O104:H4, O45:H2, O103:H2, O111:H8, and O121:H2 can also cause disease.

Stx, as a protein toxin and also an exotoxin, possesses enterotoxicity, cytotoxicity, and neurotoxicity. It is one of the most potent toxins known today and plays a crucial role in the pathogenesis of EHEC [32]. The toxin can be divided into two categories: Stx1, which can be neutralized by anti-Stx, and Stx2, which cannot be neutralized by anti-Stx. Among them, Stx2 has a much higher cytotoxicity to human glomerular microvascular endothelial cells than Stx1, with its half lethal dose (LD50) being only 1/400 that of Stx1. In the development of hemorrhagic enteritis and hemolytic uremic syndrome, the role of Stx2 is even more critical [33]. Stx-induced cytotoxicity begins with ribosomal inactivation and free A-subunit toxicity, progressing to endothelial damage in the gut and kidneys [34].

Due to the close association between Stx and EHEC pathogenesis, in scientific literature, when discussing related strains, the terms Shiga toxin-producing E. coli (STEC) and EHEC are frequently used interchangeably [35]. However, although they appear similar, there are fundamental differences between the two. According to the authoritative definition by the Food and Agriculture Organization of the United Nations, STEC refers to strains containing the Stx gene (one or more) encoding Stx but not necessarily carrying other virulence genes. EHEC, on the other hand, is defined as strains that contain both the Stx gene and an adhesion factor [36]. In most cases, once the human body ingests EHEC strains, it will trigger a series of symptoms. When the condition is mild, it manifests as bloody diarrhea and hemorrhagic colitis. If the condition worsens, it can even develop into a potentially fatal HUS [37].

3.1.2 ETEC

ETEC is one of the most common causes of diarrhea. It frequently occurs in the colon of both domestic and wild animals, even humans, leading to the death of newborn calves and piglets due to severe neonatal diarrhea, meanwhile posing a significant health threat to people in low-income and middle-income countries [38].

ETEC produces various adhesins, such as CFA/I and CFA/II, which are flagellum-like structures. These adhesins can specifically recognize and bind to receptors on the surface of small intestinal epithelial cells, allowing bacteria to adhere tightly to the intestinal mucosa [39]. This process helps ETEC resist the flushing action of intestinal peristalsis and digestive fluids, enabling it to colonize the small intestine and create conditions for subsequent pathogenic processes.

Exotoxins are crucial for the ability of ETEC to proliferate within the host and spread to other potential hosts. Different ETEC strains have multiple combinations of exotoxins, which determine their overall virulence, with the most significant being heat-labile toxins and heat-stable toxins [40]. Heat-labile toxins bind to receptors on the surface of small intestinal epithelial cells, activating adenylate cyclase, increasing intracellular cyclic adenosine monophosphate levels, inhibiting the absorption of sodium, chloride, and water by the intestinal mucosa, promoting secretion of intestinal fluid, and causing diarrhea. Heat-stable toxins bind to guanylate cyclase receptors on small intestinal epithelial cells, increasing intracellular 3′-5′-cyclic guanosine monophosphate levels, affecting ion transport, promoting secretion of intestinal fluid, and triggering diarrhea [41].

3.1.3 UPEC

UPEC belongs to the extraintestinal pathogenic E. coli, rather than the traditional intestinal pathogenic E. coli. UPEC is generally recognized as the primary pathogen causing urinary tract infections [42].

The pili of UPEC assists in adhering to epithelial cells, allowing the bacteria to firmly attach to urinary tract tissues and avoid being washed away by urine, thus achieving colonization in the urinary system. Subsequently, periodic morphological changes occur, such as filamentation. This process not only helps evade the body’s immune system but can also lead to false-negative test results, playing a crucial role in the development of urinary tract infections [43]. Additionally, UPEC has the ability to secrete extracellular polysaccharides and other substances, which can aggregate to form a biofilm that tightly encapsulates the bacteria. The microenvironment created by the biofilm provides excellent protection for the bacteria, enhancing their resistance to the host’s immune defense system, making it difficult for immune cells to approach and eliminate them. On the other hand, the biofilm can impede antibiotic penetration, preventing the complete eradication of bacteria, ultimately leading to chronic infections with frequent recurrence, significantly increasing the difficulty of treatment [44].

The virulence factors of UPEC mainly include α-hemolysin and cytotoxin-associated protein. The α-hemolysin is encoded by the hlyA gene and secreted outside the cell via the Type I secretion system. It acts as a pore-forming toxin by recognizing and binding to host cell membrane receptors. It then inserts into the cell membrane to form transmembrane pores, cause the leakage of intracellular ions and small molecules, disrupt the ion and osmotic balance within the cell, and finally lead to cell swelling and rupture [45].

Cytotoxin-associated protein consists of three subunits: CdtA, CdtB, and CdtC. Among these, CdtB is the active subunit with nuclease activity. After binding to surface receptors on the host cell, it enters the cell through endocytosis, and CdtB is transported to the nucleus where it cleaves host DNA, inducing double-strand breaks in DNA, activating signaling pathways that lead to cell cycle arrest and apoptosis. It also disrupts the urinary tract mucosal barrier, interferes with immune cell function, and facilitates the survival and proliferation of UPEC within the host [46].

3.2 Epidemiology and health effects of pathogenic E. coli

Pathogenic E. coli is widely prevalent globally, with its primary sources of infection being carriers and patients. These individuals excrete large amounts of bacteria through their feces, contaminating water sources, food, and everyday items. Foodborne transmission is the most common route. For instance, consuming undercooked contaminated meat, eggs, dairy products, and other items can easily lead to infection [47]. Additionally, close contact between people or touching contaminated objects also facilitates the spread of pathogenic E. coli. Children, the elderly, and individuals with weakened immune systems, are more susceptible and at higher risk of infection [48]. Some strains may also be more likely to infect certain genders. For example, UPEC, due to anatomical factors such as a shorter urethra which facilitates bacterial entry into the bladder, women have a significantly higher risk of urinary tract infections [49].

Pathogenic E. coli is a type of intestinal bacterium that poses a serious threat to human health. Based on their pathogenic mechanisms, they can be categorized into several types, each causing varying degrees of health issues. In addition to the three strains highlighted earlier, there are many other pathogenic E. coli strains. For example, EIEC can invade the intestinal mucosal epithelial cells, proliferate extensively within the cells, and destroy them, triggering inflammatory responses. Patients may experience fever, tenesmus, abdominal pain, bloody stools, and other symptoms similar to those of bacterial dysentery, severely affecting normal intestinal function [50]. EAEC grows in clusters within the intestine, producing toxins and invasive proteins that damage the microvilli structure of the intestine. They could impact nutrient absorption and cause persistent diarrhea, vomiting, dehydration, and long-term infection that can lead to delayed growth and development in children [51]. DAEC can adhere to intestinal epithelial cells in a diffuse manner, potentially associated with chronic diarrhea and urinary tract infections. Some strains may also cause bacteremia, affecting the entire body [52].

Such infections exhibit significant differences across regions. In developing countries, ETEC, EPEC, and EAEC strains often cause severe diarrhea in infants and young children, which can be fatal without timely medical intervention, whereas cases in developed countries typically have milder symptoms and are easier to manage [53]. Notably, recent trends show a new distribution of infection types, with EHEC and EAEC gradually becoming the primary pathogenic strains. Infections caused by these pathogens are significantly associated with foodborne disease outbreaks in industrialized nations [54].

3.3 Clinical challenges of pathogenic E. coli

Pathogenic E. coli presents numerous challenging issues in clinical practice. In terms of diagnosis, due to the varied pathogenic mechanisms and clinical manifestations of different types of pathogenic E. coli, watery diarrhea caused by enterotoxigenic E. coli can resemble symptoms of other viral infections. Hemorrhagic diarrhea caused by enterohemorrhagic E. coli is also easily confused with other intestinal diseases [55].

Moreover, some strains grow slowly or are difficult to culture under routine conditions, making rapid and accurate diagnosis extremely challenging. In treatment, antibiotics were once the primary means of therapy, but in recent years, the problem of antibiotic resistance has become increasingly severe, especially with the emergence of extended-spectrum β-lactamase (ESBL) and carbapenemase, which render common antibiotics ineffective [56]. The misuse of antibiotics may also induce enterohemorrhagic E. coli to release more toxins, increasing the risk of severe complications such as hemolytic uremic syndrome. Once cross-infection occurs in public places like hospitals, it can spread rapidly. Additionally, some patients carry the bacteria for extended periods without showing symptoms, making asymptomatic carriers difficult to detect, all of which pose significant challenges in controlling the source of infection [57].

Evaluating how to use vaccines to control E. coli would not be an easy task. Specific toxins and colonization factors may lead to ineffective prevention [58]. Accurately identifying enterotoxins and colonization factors is hard to achieve mainly due to the extensive antigenic diversity of pathogenic strains and host-specific variations, which complicate broad-spectrum protection [59].

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4. Emergence of drug-resistant E. coli

4.1 Global threat of carbapenem-resistant E. coli

Carbapenem antibiotics, such as imipenem and meropenem, are crucial in treating infections caused by multidrug-resistant Gram-negative bacteria, which were often considered the “last line of defense” due to their broad-spectrum activity [60]. However, the global dissemination of carbapenem-resistant Enterobacteriaceae began following the initial detection of New Delhi metallo-β-lactamase (NDM)-producing bacteria in India in 2009. The rapid spread of the NDM gene via mobile genetic elements, such as plasmids, has led to a surge in resistant strains within healthcare settings [61]. The proliferation of carbapenem-resistant E. coli has compelled clinicians to increasingly rely on alternative agents, including polymyxins and tigecycline. However, resistance to these drugs is also escalating, potentially leading to a “no-drug-available” scenario [62].

Resistance genes like blaNDM and blaOXA-48 are typically located on transferable plasmids which spread to different bacterial species through direct bacterial contact. NDM requires zinc ions for activity and rapidly degrades the structure of carbapenems, penicillins, and other drugs, rendering them ineffective [63]. These genes can even be transmitted from animals to humans via environmental vectors such as flies and sewage. Furthermore, NDM genes are constantly mutating (blaNDM-1 to blaNDM-9 for instance), making bacteria more resistant to newly developed antibiotics and increasing the difficulty of treatment [64].

Within hospital settings, intensive care units and surgical wards represent high-risk areas. The transmission of antimicrobial-resistant bacteria occurs through medical devices, hand contact by healthcare personnel, or patient transfer [65]. E. coli cells readily accumulate multiple resistance genes, serving as a primary transmission vector [66]. Currently, variants of the NDM gene have been identified in many countries worldwide, and international travel, medical activities, and food trade accelerate the transnational spread of resistant bacteria, posing a threat to both human and animal health [67].

Carbapenem-resistant E. coli infections lead to prolonged hospital stays and increased treatment costs. To address these challenges, a global antimicrobial resistance gene surveillance system should be established to track transmission pathways using genomic sequencing technologies [68]. In addition, developing inhibitors which target NDM enzymes [69] or utilize novel therapies like phage, antibacterial peptides would also be alternative strategies [70].

4.2 Mechanisms of antimicrobial resistance

The primary mechanism of bacterial resistance to carbapenem antibiotics involves the production of carbapenemases. These enzymes are categorized into three main types. Type 1 enzymes (KPC, IMI) exhibit resistance to inhibition by clavulanic acid or tazobactam, but are susceptible to novel inhibitors such as boronic acid derivatives. These enzymes are prevalent in the United States, Europe, and China. Type 2 enzymes are metallo-β-lactamases (NDM, VIM, IMP) that require zinc ions for activity. They hydrolyze carbapenems but do not affect aztreonam. For instance, NDM-1 has spread extensively in India and Southeast Asia, while VIM is common in several European countries. Type 3 enzymes, exemplified by OXA-48, are predominantly found in Turkey and the Middle East. These enzymes demonstrate robust activity against penicillins and are generally insensitive to most inhibitors [71].

Antimicrobial resistance (AMR) genes are horizontally transferred between bacterial species via mobile genetic elements. For instance, plasmids, such as IncF and IncP1 types, carrying genes like blaKPC-2 and blaNDM-1, facilitate direct bacterial conjugation [72]. Global surveillance indicates that NDM-producing strains have disseminated through international travel and healthcare activities.

4.3 Innovative therapies and strategies

A recent study in Chinese neonatal intensive care units has revealed that E. coli exhibits an uppermost 56.36% resistance rate to β-lactam antibiotics, primarily due to the widespread dissemination of blaCTX-M and blaTEM genes [73]. Consequently, stringent restrictions on the overuse of carbapenems are warranted, alongside the promotion of antimicrobial stewardship programs.

Researchers are actively developing adjunctive therapies to augment the efficacy of existing antibiotics. For example, nitazoxanide enhances the bactericidal effect of polymyxin B against resistant E. coli through the inhibition of bacterial fimbriae formation [74]. Furthermore, novel β-lactamase inhibitors, such as ebselen derivates, in combination with meropenem, significantly improve the clearance of NDM-1- producing Enterobacteriaceae strains [75]. New strategies such as antimicrobial peptides, fecal transplantation, and CRISPR-Cas system-mediated drug-resistant gene knockout have also entered the preclinical research stage [76].

Broad-spectrum antibiotics disrupt the normal gut microbiota, predisposing individuals to colonization by carbapenem-resistant Enterobacteriaceae. Research indicates that probiotic supplementation or modulation of gut microbiota may mitigate resistant E. coli proliferation [77]. Probiotics were believed to increase short-chain fatty acids, thereby inhibiting E. coli replication. Animal studies suggest that microbiome therapy is able to reduce the abundance of antibiotic-resistant bacteria in the gut, offering novel strategies for infection prevention [78].

Finally, enhanced surveillance and stewardship are crucial for controlling the dissemination of antimicrobial resistance. Whole-genome sequencing (WGS) can track the transmission pathways of resistance genes. During the outbreak of EHEC O104:H4 in Germany in 2011, WGS technology determined the source of the epidemic in a short time, which provided a key basis for the formulation of prevention and control measures [79]. The concept of “One Health” emphasizes the coordinated intervention of human beings, animals, and the environment, which is particularly important for controlling the spread of drug-resistant E. coli.

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5. Conclusion

As a model organism of microbiology research, E. coli shows unique dual characteristics in nature and host. In the intestines of healthy mammals, symbiotic E. coli plays an indispensable ecological function. These strains participate in the biosynthesis of various vitamins, competitively inhibit the colonization of pathogenic microorganisms, and promote the development and maturity of the host immune system through continuous antigen stimulation [80]. They also participate in the energy metabolism process of the host, helping to decompose complex polysaccharides and produce beneficial metabolites such as short-chain fatty acids [81]. In the field of biotechnology, E. coli maintains the status of “microbial workhorse”. After decades of optimization, its protein expression system has become the preferred platform for industrial production of recombinant proteins. In recent years, more complex proteins such as antibody fragment, vaccine antigen, and enzyme preparation have also been industrialized [82]. Additionally, by introducing exogenous metabolic pathways, engineered strains can produce high value-added compounds like amorphadiene, greatly reducing the production cost of this antimalarial drug [83].

The environmental adaptability of E. coli is an important basis for its dual characteristics. It can survive in a variety of environmental conditions, and this metabolic flexibility makes it an ideal model for studying bacterial environmental adaptation [84]. On the other hand, this adaptability has also brought severe public health challenges. Pathogenic E. coli strains with specific virulence factors can lead to serious infectious diseases. Among them, EHEC O157:H7 and UPEC are of greatest concern, because of their high prevalence rate and mortality rate. The emergence and spread of resistant E. coli strains has become a global health threat [85]. Through horizontal gene transfer, E. coli can quickly acquire new characters. The evolution of EHEC is a typical example, whose virulence genes mainly come from phage and virulence plasmid. This genomic plasticity not only explains its pathogenic variation, but also makes it an ideal platform for genetic engineering and synthetic biology research [86].

In the future, research regarding E. coli will focus on in-depth analysis of pathogenic mechanism with the help of single-cell sequencing and spatial transcriptomics, and the development of safer tools for gene manipulation. By leveraging cutting-edge technologies, research can transition to dynamic, spatially resolved, and single-cell mechanistic maps of E. coli pathogenesis, accelerating precision antimicrobials and host-directed therapies. Particularly, protein design assisted by artificial intelligence will optimize enzyme activity produced by E. coli. Moreover, engineered E. coli may become a “living drug”, which colonize the intestine and continuously secrete therapeutic proteins [87].

To sum up, the dual characteristics of E. coli bring both challenges and opportunities. Global cooperation is needed to monitor drug resistance. While we should also continue to tap its potential in biotechnology. Interdisciplinary integration will promote its greater contribution in the fields of environment, health, and industry (Table 1).

Useful biological toolA key component of the normal microbiota
Biological model for studying responses to varying growth conditions and ecological niches
Biopharmaceuticals synthesis
Biocatalyst for biodiesel production
Targeted delivery of drugs
Environmental remediation
Notorious pathogenIntestinal or extraintestinal infection
Urinary tract infection
Severe complications such as hus

Table 1.

Dual nature of E. coli.

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Acknowledgments

We thank the financial support by the Research Program of Qilu Institute of Technology (Grant No. QIT25TP001).

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Conflict of interest

The authors declare no conflict of interest.

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CRediT authorship contribution statement

Hui Chen: conceptualization and supervision. Yaqi Zhao: writing—original draft of Section 4. Zixuan Yan: writing—original draft of Section 3. Tianran Zhao: writing—original draft of Section 1. Yuge Liu: writing—original draft of Section 5. Lanxi Zhang: writing—original draft of Section 2. Ping Zeng: conceptualization, writing—review & editing, supervision, and funding acquisition.

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Written By

Hui Chen, Yaqi Zhao, Zixuan Yan, Tianran Zhao, Yuge Liu, Lanxi Zhang and Ping Zeng

Submitted: 28 April 2025 Reviewed: 28 July 2025 Published: 25 August 2025