Dual nature of
Abstract
This introductory chapter provides a comprehensive overview of
Keywords
- intestinal flora
- nonpathogenic strain
- pathogenic microorganism
- drug resistance
- novel therapeutics
1. Introduction
Since E.
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
In summary,
The application prospects of
2. Nonpathogenic E. coli : Biology and applications
2.1 Role in gut microbiota and gastrointestinal colonization
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
2.2 Applications as a model organism
Due to diverse growth phenotypes and adaptability of
As a widely used host for recombinant protein production, engineered
In medical application, genetically engineered
Recently, an engineered probiotic
2.3 Industrial applications
Industrially, engineered
Collectively, nonpathogenic
3. Pathogenic E. coli : Prevalence and challenges
3.1 Overview of important strains
Pathogenic E.
3.1.1 EHEC
EHEC is a type of pathogenic
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
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
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.
Pathogenic E.
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.
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
Evaluating how to use vaccines to control
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
Resistance genes like
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].
Carbapenem-resistant
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
4.3 Innovative therapies and strategies
A recent study in Chinese neonatal intensive care units has revealed that
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
Broad-spectrum antibiotics disrupt the normal gut microbiota, predisposing individuals to colonization by carbapenem-resistant
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
5. Conclusion
As a model organism of microbiology research,
The environmental adaptability of
In the future, research regarding
To sum up, the dual characteristics of
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 pathogen | Intestinal or extraintestinal infection |
Urinary tract infection | |
Severe complications such as hus |
Table 1.
Acknowledgments
We thank the financial support by the Research Program of Qilu Institute of Technology (Grant No. QIT25TP001).
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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