Escherichia coli (E. coli)

Overview

Escherichia coli (E. coli) is a facultative anaerobic, Gram-negative bacterium commonly found in the intestines of humans and animals. Escherichia coli (E. coli) is a versatile and widely studied bacterium, recognized for its role as both a harmless gut commensal and a prominent pathogen. Among its pathogenic strains, various types exhibit distinct virulence factors, mechanisms, and associated clinical conditions, which underscore the significance of E. coli in public health and microbiology. The study of E. coli’s virulence factors and metal acquisition systems is crucial for developing effective strategies to prevent and manage infections caused by this ubiquitous bacterium. Understanding these elements not only provides insights into the pathogenicity of E. coli but also highlights the potential for discovering new microbiome-targeted interventions (MBTIs).

What are the pathogenic and commensal E. coli?

Pathogenic E. coli
Notably, Uropathogenic E. coli (UPEC) is a leading cause of urinary tract infections, while Enterohemorrhagic E. coli (EHEC) strains, including the infamous O157:H7 serotype, are linked to severe gastrointestinal diseases and outbreaks, emphasizing the diversity and potential severity of infections caused by pathogenic E. coli. ^[1][2]

Pathogenic Type	Description
Enteropathogenic E. coli (EPEC)	Forms “attaching and effacing” (A/E) lesions in the intestinal epithelium, leading to diarrhea, particularly in infants and young children. [3]
Enterohemorrhagic E. coli (EHEC)	Includes serotype O157:H7, produces Shiga toxin, and is linked to hemorrhagic colitis and hemolytic uremic syndrome (HUS).[4]
Enterotoxigenic E. coli (ETEC)	Common cause of traveler’s diarrhea, produces heat-stable (ST) and heat-labile (LT) enterotoxins.[5]
Enteroinvasive E. coli (EIEC)	Causes dysentery by invading intestinal epithelial cells, leading to inflammation and ulceration.[6]
Enteroaggregative E. coli (EAEC)	Adheres to the intestinal mucosa in a stacked-brick pattern, contributing to persistent diarrhea. [7]
Diffusely Adherent E. coli (DAEC)	Associated with diarrhea in children, characterized by a diffuse adherence pattern to epithelial cells. [8]
Uropathogenic E. coli (UPEC)	Responsible for most urinary tract infections (UTIs), with virulence factors that facilitate urinary tract colonization. [9]
Neonatal Meningitis E. coli (NMEC)	Causes neonatal meningitis, with virulence factors that enable blood-brain barrier penetration.[10]
Extraintestinal Pathogenic E. coli (ExPEC)	Includes multiple pathotypes (e.g., UPEC, APEC) and causes infections outside the gastrointestinal tract, including sepsis and pneumonia.[11]
Endometrial pathogenic E. coli (EnPEC)	A poorly characterized and studied pathotype belonging to the ExPEC group that may cause endometriosis in humans and animals. [12]

Commensal & Beneficial E. coli

Strain Name	Role & Characteristics
Escherichia coli Nissle 1917 (EcN)	A well-studied probiotic strain with anti-inflammatory properties, used in treating IBD and IBS. Competes with pathogens and enhances gut barrier integrity.
Escherichia coli HS	A non-pathogenic commensal strain isolated from healthy human intestines, often used in microbiome research.
Escherichia coli K-12	A model laboratory strain derived from a gut commensal; does not colonize the human gut but is widely used in research.
Escherichia coli MG1655	A genetically sequenced derivative of K-12, often used in genetic and microbiome studies.
Escherichia coli SE15	A gut commensal strain with probiotic-like properties, shown to outcompete pathogens and support immune regulation.

Virulence Factors

The virulence of pathogenic E. coli is largely attributed to an array of specialized factors, including adhesins, toxins, and iron acquisition systems such as siderophores. These elements enable the bacteria to effectively colonize host tissues, evade immune responses, and inflict damage, thereby enhancing their pathogenicity.^[13] Siderophores, in particular, are critical for iron acquisition, a vital process for E. coli’s survival and growth, especially in iron-limited environments. ^[14][15]

What are the specific virulence factors associated with E. coli?

Virulence Factor	Mechanism & Role in Host Competition
Siderophores (Enterobactin, Yersiniabactin, Salmochelin)	Allow E. coli to scavenge iron, outcompeting host iron-sequestering proteins like lactoferrin and transferrin. [16][17][18]
Capsular Polysaccharides	Provide protection against host immune responses and complement-mediated lysis. [19]
Type 1 Pili & Fimbriae	Facilitate adherence to gut epithelium, critical for pathogenicity in UTIs and IBD-associated strains. [20]
Lipopolysaccharide (LPS)	Activates Toll-like receptor 4 (TLR4), triggering inflammation and immune system activation. [21]
Colibactin	A genotoxin linked to DNA damage and tumorigenesis in colorectal cancer. [22]
Toxins (STX, LT, ST)	Shiga toxin (STX) and heat-labile (LT)/heat-stable (ST) enterotoxins contribute to diarrheal diseases and systemic effects. [23]

Microbial Metallomics

Microbial metallomics plays a pivotal role in understanding E. coli’s functionality, as it investigates how metal ions contribute to biological processes and the bacterium’s adaptation to varying environmental conditions. ^[24] E. coli’s metal ion homeostasis mechanisms have been shown to be crucial for maintaining cellular stability and functionality, particularly during pathogenic interactions.^[25] The metallomics of E. coli reveals a complex network of metal acquisition, homeostasis, and virulence mechanisms that allow it to thrive in diverse environments, including the human gut, urinary tract, and contaminated food sources. Understanding E. coli‘s metal metabolism is critical for developing new antimicrobial strategies that exploit its dependency on essential metals.

Nutritional Immunity

Recent research has revealed that E. coli employs sophisticated mechanisms to overcome host nutritional immunity, illustrating the intricate evolutionary dynamics between bacterial pathogens and their hosts. ^[31]Host nutritional immunity restricts iron availability to control microbial proliferation, but E. coli circumvents this by producing high-affinity siderophores that outcompete host iron-binding proteins like lactoferrin and transferrin. This metallomic competition enhances E. coli’s survival, particularly in inflamed environments where iron sequestration is a primary host defense mechanism.

Associated Conditions

Associated Conditions	Relevance
Endometriosis	Major Microbial Association MMA

Is all E. coli dangerous?

No, most E. coli strains are harmless and even beneficial, residing in the intestines where they aid digestion, synthesize vitamins (such as vitamin K), and outcompete harmful bacteria. However, pathogenic strains, such as Enterohemorrhagic E. coli (EHEC) and Uropathogenic E. coli (UPEC), can cause severe diseases, including bloody diarrhea, hemolytic uremic syndrome (HUS), and urinary tract infections.

How does E. coli acquire iron when the human body restricts it?

E. coli has evolved sophisticated iron-scavenging mechanisms to counteract the host’s nutritional immunity. It produces siderophores, high-affinity iron-chelating molecules, that steal iron from host proteins like transferrin and lactoferrin. Some E. coli strains even pirate siderophores from other bacteria, giving them a competitive advantage.

Can E. coli become antibiotic-resistant?

Yes, and it’s a growing public health concern. Some E. coli strains, especially in hospitals, carry extended-spectrum beta-lactamases (ESBLs), making them resistant to penicillins and cephalosporins. Others, like New Delhi metallo-beta-lactamase (NDM-1) producing strains, are resistant to nearly all available antibiotics, making infections extremely difficult to treat.

References

1. Differences of virulence factors, and antimicrobial susceptibility according to phylogenetic group in uropathogenic Escherichia coli strains isolated from Korean patients.. Hyun, M., Lee, J.Y. & Kim, H.. (Ann Clin Microbiol Antimicrob 20, 77 (2021).)
2. Characterization of siderophores from Escherichia coli strains through genome mining tools: an antiSMASH study.. Cavas, L., Kirkiz, I.. (AMB Expr 12, 74 (2022).)
3. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog, 2024.)
4. Fitness of Escherichia coli during urinary tract infection requires gluconeogenesis and the TCA cycle.. Alteri CJ, Smith SN, Mobley HL.. (PLoS Pathog. 2009)
5. Heat-Stable Enterotoxins of Enterotoxigenic Escherichia coli and Their Impact on Host Immunity.. Wang H, Zhong Z, Luo Y, Cox E, Devriendt B.. (Toxins (Basel). 2019.)
6. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog. 2024.)
7. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog. 2024.)
8. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog. 2024.)
9. Heat-Stable Enterotoxins of Enterotoxigenic Escherichia coli and Their Impact on Host Immunity.. Wang H, Zhong Z, Luo Y, Cox E, Devriendt B.. (Toxins (Basel). 2019.)
10. A Review on Virulence Factors of Escherichia Coli.. Eshetu Shumi Gebisa, Minda Asfaw Gerasu, Diriba Taddese Leggese.. (Anim Vet Sci. 2019.)
11. Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle. Christopher J. Alteri,Sara N. Smith,Harry L. T. Mobley. (PLOS Pathogens. 2009)
12. Insights on the genetic features of endometrial pathogenic Escherichia coli strains from pyometra in companion animals: Improving the knowledge about pathogenesis.. C.E. Lopes, S. De Carli, M.N. Weber, A.C.V. Fonseca, N.J. Tagliari, L. Foresti, S.P. Cibulski, F.Q. Mayer, C.W. Canal, F.M. Siqueira. (Infection, Genetics and Evolution, Volume 85, 2020,)
13. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog 16, 57 (2024).)
14. A Review on Virulence Factors of Escherichia Coli.. Eshetu Shumi Gebisa, Minda Asfaw Gerasu, Diriba Taddese Leggese.. (Anim Vet Sci. 2019.)
15. Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports.. Sarowska, J., Futoma-Koloch, B., Jama-Kmiecik, A. et al.. (Gut Pathog 11, 10 (2019).)
16. Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982–2024) and food safety criteria.. Alhadlaq, M.A., Aljurayyad, O.I., Almansour, A. et al.. (Gut Pathog. 2024.)
17. A Review on Virulence Factors of Escherichia Coli.. Eshetu Shumi Gebisa, Minda Asfaw Gerasu, Diriba Taddese Leggese.. (Anim Vet Sci. 2019.)
18. Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports.. Sarowska, J., Futoma-Koloch, B., Jama-Kmiecik, A. et al.. (Gut Pathog, 2019.)
19. Differences of virulence factors, and antimicrobial susceptibility according to phylogenetic group in uropathogenic Escherichia coli strains isolated from Korean patients. Hyun, M., Lee, J.Y. & Kim, H.. (Ann Clin Microbiol Antimicrob, 2021.)
20. Adherence patterns of Escherichia coli in the intestine and its role in pathogenesis.. Deenadayalan Karaiyagowder Govindarajan, Nandhini Viswalingam, Yogesan Meganathan, Kumaravel Kandaswamy. (Medicine in Microecology, 2020.)
21. Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway and proinflammatory response in human pericytes.. Guijarro-Muñoz I, Compte M, Álvarez-Cienfuegos A, Álvarez-Vallina L, Sanz L.. (J Biol Chem. 2014.)
22. Genotoxins: The Mechanistic Links between Escherichia coli and Colorectal Cancer.. Wang Y, Fu K.. (Cancers (Basel). 2023.)
23. Pathogenic Escherichia coli.. Kaper, J., Nataro, J. & Mobley, H.. (Nat Rev Microbiol. 2004.)
24. Variation in Siderophore Biosynthetic Gene Distribution and Production across Environmental and Faecal Populations of Escherichia coli.. Searle LJ, Guillaume Méric, Porcelli I, Sheppard SK, Lucchini S.. (PLoS ONE. 2015.)
25. A Review on Virulence Factors of Escherichia Coli.. Eshetu Shumi Gebisa, Minda Asfaw Gerasu, Diriba Taddese Leggese.. (Anim Vet Sci. 2019.)
26. Role of Nickel in Microbial Pathogenesis.. Maier RJ, Benoit SL.. (Inorganics. 2019.)
27. Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence.. Porcheron G, Garénaux A, Proulx J, Sabri M, Dozois CM.. (Front Cell Infect Microbiol. 2013)
28. Bacterial resistance to carbapenems.. Livermore DM.. (Adv Exp Med Biol. 1995)
29. Roles of the extraintestinal pathogenic Escherichia coli ZnuACB and ZupT zinc transporters during urinary tract infection.. Sabri M, Houle S, Dozois CM.. (Infect Immun. 2009)
30. High dietary zinc feeding promotes persistence of multi-resistant E. coli in the swine gut.. Ciesinski L, Guenther S, Pieper R, Kalisch M, Bednorz C, Wieler LH.. (PLoS One. 2018.)
31. The impact of species, respiration type, growth phase and genetic inventory on absolute metal content of intact bacterial cells.. Rohit Budhraja, Ding C, Walter P, et al.. (Metallomics, 2019.)