MICROBIOLOGY


set the stage for recognising STEC as a unique group of pathogenic E. coli. The first recorded outbreak was in 1982 in the United States where undercooked hamburgers were linked to haemorrhagic colitis. The implicated strain, later designated as O157:H7, produced Shiga toxins and caused severe clinical manifestations including HUS.6


This


outbreak prompted extensive research into STEC’s epidemiology, virulence factors, and prevention.


n Advances in molecular biology and genomic characterisation The complete sequencing of the O157:H7 genome in 2001 provided critical insights into STEC pathogenicity. Scientists identified bacteriophage- encoded Shiga toxin genes (stx1 and stx2), and the locus of enterocyte effacement (LEE), which encodes a type III secretion system (T3SS) essential for intimate adherence to intestinal cells.7 Although the O157:H7 serotype


remains the classical strain for STEC infections, advanced molecular and immunologic diagnostic methods have since uncovered a broad diversity of non-O157 STEC strains, the most common of these – often referred to as ‘the big six’ – are strains O26, O45, O103, O111, O121, and O145, now recognised as significant contributors to the global STEC disease burden.8


Pathogenicity of STEC Clinically, STEC infections typically begin as gastrointestinal disturbances characterised by watery diarrhoea, abdominal pain, and vomiting. As the infection progresses, many patients develop bloody diarrhoea. In severe disease states that may be life threatening, HUS can emerge. This is characterised by acute kidney injury, thrombocytopenia, and microangiopathic haemolytic anaemia. HUS is most commonly seen in young children, the elderly, and the immunocompromised. Although less common, there can be neurotoxic effects of Shiga toxins which may lead to encephalopathy, seizures, and long-term cognitive deficits. Evidence suggests that the Shiga toxins may cross the blood-brain barrier.9 STEC’s virulence is determined by a sophisticated array of factors that facilitate host colonisation, disrupt cellular processes, and subvert immune defences. The Shiga toxins are the main characteristic of virulence. Classified as an AB₅ toxin, these molecules consist of one enzymatically active A subunit and five B subunits that bind to the host cell glycolipid receptors, globotriaosylceramide (Gb3).10


Once 40


Year Location 1996 Scotland


2005 Wales


Confirmed cases Deaths Source 279


17 157


2009 Godstone Farm, 93 England


2016 Nationwide 2022 Nationwide 165 259 Table 1. Major UK E. coli O157 Outbreaks.


internalised, the A subunit inactivates the 60S ribosomal subunit by removing a specific adenine from the 28S rRNA, thereby halting protein synthesis and inducing cell death.11


Among the two


primary toxins, stx2 is usually more virulent than stx1. Moreover, specific subtypes stx2a and stx2c have been strongly associated with the development of HUS. This variability in toxin potency is a key determinant of clinical outcomes. The high expression of Gb3 on renal endothelial and neural tissues explains STEC’s tendency for causing kidney injury and, in some instances, neurological complications. The combination of endothelial damage and a significant inflammatory response predispose for the onset of the microangiopathic haemolytic anaemia and thrombocytopenia characteristic of HUS.12 The locus of enterocyte effacement (LEE) is another significant virulence factor. This pathogenicity island encodes a type III secretion system (T3SS) that injects effector proteins directly into the host cells. These effectors disrupt cytoskeletal architecture and manipulate host signalling pathways, leading to the formation of attaching and effacing (A/E) lesions. These lesions not only promote bacterial adhesion but also compromise the intestinal barrier, thereby facilitating the systemic spread of Shiga toxins and other virulence factors.13


In addition to these mechanisms, several adhesins and colonisation factors contribute to STEC’s pathogenicity. The outer membrane adhesin intimin, encoded by the eae gene, interacts with the translocated intimin receptor (Tir) which is inserted into the host cell’s membrane via the T3SS.14


Other factors,


such as the STEC autoagglutinating adhesin (Saa), promote bacterial aggregation and persistence, and in some strains, biofilm formation enhances environmental resistance, complicating efforts to control STEC in food processing and clinical settings.


STEC also employs several strategies


to evade immune detection and clearance. Some strains produce factors that inhibit complement activation, reduce neutrophil-mediated phagocytosis, or modulate cytokine responses.15


While the inflammatory


response aims to clear the pathogen, an excessive response can contribute to tissue damage, particularly in the kidneys, worsening the clinical severity of HUS.


Epidemiology of STEC A thorough understanding of STEC epidemiology requires an examination of its transmission pathways, outbreak dynamics, and regional variability. Globally, contaminated food products, particularly undercooked meats, unpasteurised dairy, and fresh produce serve as the primary infection routes for STEC transmission. Cross-contamination during food processing further heightens the risk. In addition, agricultural run-off and inadequate water treatment can disseminate STEC via contaminated water sources. Direct contact with wildlife and in particular cattle (or their faeces) remains a significant transmission route. Person-to- person spread is also observed, especially in closed settings seen in some daycare centres and care homes where hygiene practices may be suboptimal. STEC was recognised as a human pathogen in 1982 in the US when two different outbreaks of haemorrhagic colitis were seen. The causative organism in both outbreaks was the O157:H7 strain and its association with HUS was identified in 1983.16


Since then, STEC has


been identified in epidemiological studies around the globe as a significant cause of bloody diarrhoea and HUS, primarily in children, but also in the elderly, and immunocompromised individuals.


STEC O157 epidemiology There have been a number of outbreaks causing morbidity and mortality associated with STEC O157:H7 with each having a subsequent impact on


APRIL 2025 WWW.PATHOLOGYINPRACTICE.COM 1 0 2 0 Key outcomes


Contaminated meat


Contaminated cooked meats


Petting farm animals


Various foods implicated


Contaminated lettuce


Led to greater food safety awareness


Stricter food


hygiene regulations Improved hygiene


measures at petting farms Enhanced monitoring in


catering and care homes Stricter agricultural


safety measures


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56