Abstract
Extraintestinal pathogenic E. coli (ExPEC) present a major clinical problem that has emerged in the past years. Most of the infections are hospital or community-acquired and involve patients with a compromised immune system. The infective agents belong to a large number of strains of different serotypes that do not cross react. The seriousness of the infection is due to the fact that most of the infecting bacteria are highly antibiotic resistant. Here, we discuss the bacterial factors responsible for pathogenesis and potential means to combat the infections.
Access provided by CONRICYT-eBooks. Download chapter PDF
Similar content being viewed by others
Keywords
- Extraintestinal Pathogenic E. Coli (ExPEC)
- ExPEC Strains
- Avian Pathogenic E. Coli (APEC)
- Type Three Secretion System (TTSS)
- ColV Plasmid
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
1 Introduction
Although most strains of Escherichia coli are commensals and abundant, many strains are virulent. In addition to the well-established role of E. coli as the causative agent of intestinal infections, many virulent strains cause extraintestinal infections.
The importance of ExPEC is increasing rapidly because they are abundant and are highly resistant to antibiotics. Many of the ExPEC infections are associated with immunodeficiency due to very young age (neonatal), old age, chemotherapy, or diseases that weaken the immune system, such as HIV. Thus, as a human pathogen, ExPEC are the leading causative agents in hospital- and community-acquired infections (healthcare-associated infections). According to the WHO (Healthcare-associated infections FACT SHEET), “hundreds of millions of patients are affected by health care-associated infections worldwide each year, leading to significant mortality and financial losses for health systems. Of every 100 hospitalized patients at any given time, 7 in developed and 10 in developing countries will acquire at least one health care-associated infection.” The estimated cost of treating healthcare-associated infections is about 20 billion US$ a year.
ExPEC bacteria are involved in infections of humans and farm animals. They are often classified as APEC (avian pathogenic E. coli), UPEC (E. coli causing urinary tract infections = UTI), NMEC (neonatal meningitis-causing E. coli), or septicemic. However, although this classification is sometimes convenient, it is actually meaningless because there is much overlap between the groups (Ron 2006). Several examples include APEC strains, such as E. coli serotype O2 which are a frequent cause of UTI; E. coli serotype O18 that is involved in avian colisepticemia and human newborn meningitis (Ewers et al. 2007; Krishnan et al. 2015; Nicholson et al. 2016; Tivendale et al. 2010) and UPEC strains often become septicemic. The similarities between the human and animal strains can also be characterized at the genomic level (Bauchart et al. 2010; Maluta et al. 2014; Zhu Ge et al. 2014) and multilocus sequence typing (MLST) of E. coli O78 strains indicate that several isolates from newborn meningitis cluster with avian septicemic isolates (Adiri et al. 2003). The similarity between ExPEC strains involved in animal infections and human infections raises the possibility of zoonosis. This possibility is difficult to prove, but it should certainly be considered especially for the transfer of antimicrobial-resistant ExPEC through contaminated food (Manges 2016).
In a few cases where host specificity was documented, it appears to involve specificity of adherence. Such specificity can be shown in clinical isolates of E. coli serogroup O78—human intestinal strains produce the human-specific adherence fimbria CFA/I that bind specifically to intestinal epithelia (Buhler et al. 1991; Cheney and Boedeker 1983), isolates from septicaemia of lambs produce the P, S, and F1C adhesins (Dozois et al. 1997) or the K99 fimbriae (E. Z. Ron. Unpublished), and some O78 isolates from avian colispeticemia code for avian-specific fimbriae (AC/I pili, belonging to the group of S-fimbriae) (Babai et al. 1997, 2000; Dobrindt et al. 2001; Yerushalmi et al. 1990).
Here, we will discuss ExPEC strains and the genetic and physiological factors that promote the virulence.
2 Infections Involving ExPEC
2.1 Avian Colisepticemia
This is an important disease in poultry leading to losses of millions each year to the poultry industry. This disease is characteristic for birds under stress—high temperature, high humidity, or mild viral infections, even due to vaccinations. The disease starts from the upper respiratory tract and the bacteria enter the bloodstream, are dispersed in the body and infect vital organs. This infection involves high morbidity and mortality. The majority of infections (about 80%) are caused by E. coli serotypes O1, O2, and O78 but many additional serotypes were shown to be involved (Cordoni et al. 2016; Dho-Moulin and Fairbrother 1999; Dziva et al. 2013; Huja et al. 2015; Mangiamele et al. 2013; Mellata et al. 2009; Nicholson et al. 2016; Rodriguez-Siek et al. 2005; Sola-Gines et al. 2015).
2.2 Veterinary Infections
ExPEC are the cause of several diseases of calves and lambs. The bacteria infect the newborns and cause a lethal septicemia (Ansari et al. 1978; Duff and Hunt, 1989; Kjelstrup et al. 2013). Apparently, these diseases are not of major veterinary impact.
2.3 Neonatal Meningitis
NMEC (Neonatal meningitis-causing E. coli) are the major Gram-negative pathogens associated with meningitis in newborn infants (Czirok et al. 1977; Milch et al. 1977; Wijetunge et al. 2015a, b). This group includes several serotypes such as O1, O18 (Wijetunge et al. 2015a, b), and O78 (Czirok et al. 1977; Milch et al. 1977). Although quite rare (1 per 1000 births in developing countries and 1 per 10,000 in developed countries) it is severe, as it involves a very high mortality rate.
2.4 Urinary Tract Infections (UTI)
UTI is the most common ExPEC infection (Ejrnaes 2011; Ena et al. 2006; Foxman 2010, 2014; Jacobsen et al. 2008; Marrs et al. 2005; Zhang and Foxman 2003). In 2007, there were in the US about 10 million ambulatory visits and about 2 million admissions to hospital emergency departments (Foxman 2010, 2014). It is very common in young women, where the infection can become recurrent, and in older patients following catheterization. UTIs can get complicated and cause kidney failure and quite often, especially in the elderly, lead to bloodstream infections such as sepsis.
2.5 Blood Stream Infections/Septicemia/Sepsis
This ExPEC infection is the most serious one in terms of severity as well as an economic burden. Every year there are more than a million cases of sepsis in the US and the estimate is that about 30% of them die. This number is higher than deaths in the US due to prostate cancer, breast cancer, and HIV combined (Sepsis Fact Sheet, CDC, 2016). In 2011, the US spent $20.3 on hospital care for sepsis patients—about 55 million US$ a day and the cost per patient can be as high as 56,000 US$. Sepsis is clearly an emerging disease as the number of cases per year increases rapidly. There are several reasons for this escalation such as the increased longevity of people, the broader use of invasive procedures, immunosuppressors, and chemotherapy. But probably the most important reason for the current situation is the fast spread of antibiotic-resistant E. coli, the major cause of sepsis.
3 Virulence Factors
A general feature of ExPEC is that production of exotoxins is not a major factor in their virulence, in contrast to many intestinal strains. There is evidence for production of cytotoxin by ExPEC, but it is not clear if they are important for pathogenicity (De Rycke and Oswald 2001; Peres et al. 1997; Taieb et al. 2016). The virulence of ExPEC strains appears to depend on their ability to survive in host tissues, especially in serum. Many of the genes involved in virulence are present on large plasmids, most frequently on a ColV plasmid (Huja et al. 2015; Milch et al. 1984; Waters and Crosa, 1991; Wijetunge et al. 2014). The ColV plasmids are a family of related plasmids that encode a broad spectrum of iron uptake systems and genes for increased serum survival.
In general, there is an extensive variability in virulence-associated genes of ExPEC (Mokady et al. 2005a, b; Ron 2006, 2010). There appears to be a large “pool” of such genes and much overlap between them. For example—there are several genetic systems for iron acquisition and an ExPEC strain can carry one or more of them, the same for genes coding for fimbriae or adherence factors, etc. It is clear that many of the virulence factors were obtained by lateral gene transfer, such as the gene coding for Yersiniabactin, the Yersinia iron uptake system (Gophna et al. 2001; Huja et al. 2015). However, all the ExPEC strains carry at least one adherence system and septicemic strains carry at least one efficient iron-binding system and genes for serum survival (ISS—increased serum survival).
3.1 Adherence
Adherence to host cells is the initial step of an E. coli infection and is essential for invasion and infection. Adherence also influences host specificity and even tissue specificity. Thus, intestinal pathogens adhere preferentially to gut epithelium while bacteria involved in UTI adhere to bladder epithelium (Kalita et al. 2014).
Adherence depends mainly by specific organelles—pili, or fimbriae—that recognize specific ligands on the epithel. Infections of mammalian farm animals (cattle, sheep, pigs, etc.) begin by intestinal colonization of newborn and often involve K99 and K88 pili and AC/I pili were found only in APEC and show specificity to chicken tracheal epithelium (Babai et al. 2000; Yerushalmi et al. 1990). The most common fimbriae in strains involved in UTI/sepsis are the P-fimbriae that bind glycolipids containing a-D-Gal-1,4-b-D-Gal (Korhonen et al. 1982; Lane and Mobley 2007; Lund et al. 1988; Stromberg et al. 1990), F1C fimbriae, which bind b-GalNac-1,4-bGal (Khan et al. 2000; van Die et al. 1991) and fimbriae of the S-family. The S-family includes the SfaI, SfaII, Foc, and AC/I fimbriae. The Sfa fimbrial adhesins are produced by strains involved in sepsis and newborn meningitis and interact with glycoproteins containing sialic acid (Babai et al. 2000; Bauchart et al. 2010; Dobrindt et al. 2001; Hacker et al. 1985; Moch et al. 1987; Parkkinen et al. 1986). The group of S-fimbriae is interesting as there is evidence for horizontal gene transfer and combinatorial gene shuffling resulting in pili with different adherence specificities that are related to the clinical symptoms or the host. Thus, the sfaAII gens (from a NBM strain) is homologous to the facA gene of AC/I pili (APEC) while the sfaIIS gene—coding for the adhesion—is homologous to this of the sfaI cluster from a human sepsis strain (Babai et al. 2000). The combinatorial shuffling of fimbrial genes is probably of ecological and functional importance as it increases the fimrial diversity to improve adaptation to different hosts and resistance to the immune system of the host. Moreover, many of the ExPEC strains express more than one type of fimbriae and the expression of fimbrial genes appears to be coordinated, also important for diversity and increase the probability of survival under changing environmental conditions (Holden and Gally 2004).
3.2 Type Three Secretion Systems (TTSS)
Type three secretion systems are needle-like structures used to secrete effector proteins into host cells. The TTSS of intestinal pathogenic E. coli, especially the LEE system, have been well characterized. ExPEC strains do not have an LEE system but do have a homologous gene cluster—ETT2 = E. coli Type Three secretion system 2, similar to the SPI1 pathogenicity island of Salmonella. It is present in the majority of ExPEC strain from humans and animal farms (Cheng et al. 2012; Hartleib et al. 2003; Ren et al. 2004; Wang et al. 2016b). However, the ETT2 gene clusters carry a large number of mutations and deletions and it is not even clear how many of the strains express the ETT2 genes (Ideses et al. 2005; Ren et al. 2004). So far, there is no evidence that the ETT2 system is a secretion system, as no secreted proteins have been detected (Hu et al. 2017). Yet, in E. coli O157:H7 it encodes regulators that affect expression of genes in the LEE gene cluster (Zhang et al. 2004), and in avian E. coli O78, the ETT2 system affects motility (Wang et al. 2016a). The ETT2 system of E. coli O78-9 is degenerate, as it carries a large deletion and several point mutations. Yet, it is critical for virulence and for serum resistance (Huja et al. 2015; Ideses et al. 2005; Wang et al. 2016a). Recently it was shown that ETT2 has a global effect on the cells surface and is involved in secretion of flagella and fimbriae, in production of outer membrane vesicles and multicellular behaviour (Shulman et al. 2018).
4 Avoiding the Immune Response
ExPEC strains are characterized by high resistance to serum, which contains antibodies and complement. The complement complex mediates direct killing by the formation of pores in the cell membrane. Pathogens evolved outer surface features that inhibit complement-dependent killing, such as lipopolysaccharides and capsules, which are the important factors involved in serum resistance (Phan et al. 2013)
4.1 Lipopolysaccharides—LPS
Complete lipopolysaccharides are essential for serum survival and pathogenicity of ExPEC (Hammond 1992; Kusecek et al. 1984). However, because a very large number of LPS serotypes are involved in septicemia, there does not appear to be an advantage for specific serotypes. An important factor is the length of the O-antigen chain, which also influences the level of serum resistance (Grozdanov et al. 2002)
4.2 Capsules
The capsules produced by E. coli strains are divided into four groups according to their composition and biosynthesis (Whitfield and Roberts 1999). Capsules of group 1, 2, and 3 have been extensively studied, they are acidic polysaccharides composed of oligosaccharide repeating units and their role in virulence is well established. (Buckles et al. 2009; Goller and Seed 2010; Hafez et al. 2009; Kim et al. 2003; Sarkar et al. 2014). Capsules belonging to group 4—also called “O-antigen capsules” have only recently been studied and shown to contribute to enteropathogenic E. coli resistance to human alpha-defensin 5 (Thomassin et al. 2013) to shield intimin and the type three secretion system of intestinal pathogenic E. coli (Shifrin et al. 2008) and to facilitate spreading of Shigella sonnei to peripheral organs (Caboni et al. 2015). Its essential role for virulence was shown in avian ExPEC strain serotype O78 when a transposition that abolished capsule synthesis resulted in reduced virulence (Dziva et al. 2013). Moreover, a precise deletion of the etp gene involved in the biosynthesis of the group 4 capsule resulted in serum sensitivity (Biran and Ron 2017). Thus, it is clear that O-antigen/group 4 capsule is also a critical virulence factor for the spread of bacteria in the bloodstream and for septicemia.
4.3 ISS—Increased Serum Survival
Studies in avian pathogenic E. coli indicated that a gene present in the ColV plasmid confers serum resistance (Binns et al. 1979). This gene—called iss for increased serum survival—encodes a small membrane protein (Binns et al. 1982; Horne et al. 2000; Nolan et al. 2002, 2003). This gene is homologous to the bor gene of E. coli K-12 that originated from bacteriophage λ (Johnson et al. 2008; Lynne et al. 2007). It is clear that the iss gene is a major factor in serum survival (Binns et al. 1982; Huja et al. 2015; Nolan et al. 2002, 2003). Yet, the molecular basis for its role in serum survival is not clear. Moreover, a deletion of the iss gene from the ColV plasmid results in serum sensitivity and is not complemented by the chromosomal iss (bor) gene (Huja et al. 2015). This finding is difficult to explain, as the chromosomal gene codes for the homologous protein as the plasmid gene.
5 Avoiding Metabolic Immunity
As already noted, to survive in serum, bacteria must overcome the innate immunity of the host, mainly the effect of the complement system. However, another obstacle is the nutritional immunity of the serum caused by the fact that nutrients are bound in storage molecules and are unavailable to the bacteria (Weinberg 2009). Most significant is the limitation in iron, which is bound in the blood to human proteins (such as ferritin, hemosiderin) Therefore, most of the ExPEC strains contain genes involved in iron sequestering and it is clear that iron acquisition systems and receptors play a pivotal role in the virulence of septicemic pathogens. Indeed, systems-wide analyses of the response of septicemic bacteria to serum show an induction of the genes involved in iron metabolism and controlled by the iron homeostasis regulator Fur (Huja et al. 2014). It appears that the presence of multiple iron acquisition systems is essential, but just as important is their precise regulation upon exposure to serum. Thus, the nonpathogenic E. coli K-12 grows poorly even in serum in which the complement system has been heat inactivated, and its iron metabolism is not induced upon exposure to serum (Otto et al. 2016). Furthermore, these bacteria grow much better in the presence of serum (inactivate) upon introduction of the fur gene from septicemic strains (Otto et al. 2016).
Functional genomic analyses indicate that exposure to serum changes the expression of a large number of genes, most of which are induced even in the absence of active complement (Huja et al. 2014). Therefore, it is clear that overcoming the nutritional immunity is an essential step for surviving serum and establishing a bloodstream infection.
6 Concluding remarks and future perspectives
ExPEC—Extraintestinal Pathogenic E. coli constitute a clinical problem of increasing importance. Yet, our understanding of the pathogenesis of these bacteria is quite limited. As they do not appear to produce potent secreted toxins, their ability to cause infection depends on their ability to survive and multiply in the host. In order to overcome hostile environments, such as the urinary tract or even blood where they are exposed to innate immunity and nutritional immunity, a whole series of functions and regulatory mechanisms were evolved. The role of most of these functions and regulations in infection is not clear yet, but it is evident that the majority of these is important for overcoming the nutritional immunity and not only the innate immunity.
Why are ExPEC strains so difficult to combat? There are several major reasons, which are as follows:
-
1.
The extraintestinal infections involve a very large number of serotypes that do not cross react. Therefore, simple vaccines comprising several strains are not feasible. In addition, if there is a vaccine—who should be vaccinated? As in most cases, the infection is opportunistic, often following a medical intervention, it is difficult to define the population at risk.
-
2.
ExPEC carry a variety of genes coding for drug resistance, which are often on conjugative plasmids that easily spread in the whole bacterial population. Moreover, ExPEC are present in large number in the intestine, where they encounter bacteria, such as Klebsiella and Acinetobacter from which they can get resistance genes by horizontal gene transfer.
-
3.
The search for new anti-ExPEC targets is a real challenge, as many of the genes involved in pathogenesis have overlapping activities, and inhibiting one of them will probably be insufficient to prevent the infection. For example—in order to overcome the deprivation of iron in serum, ExPEC strains code for several efficient iron binding systems, most of which were obtained by horizontal gene transfer. In order to prevent ExPEC from resisting serum, it should probably be necessary to inhibit all of these iron acquisition systems.
-
4.
Once the bacteria enter the bloodstream the infections progress very quickly, with the bacteria getting to the vital organs and reaching high numbers. As E. coli contains the endotoxic cell envelope of lipopolysaccharides, the patients are exposed to critical danger even only from the endotoxin of dead bacteria.
In conclusion—it is essential to identify new targets for developing drugs or vaccines and, in parallel, to develop means that can constitute early warning systems, especially in hospital and community institutions.
References
Adiri RS, Gophna U, Ron EZ (2003) Multilocus sequence typing (MLST) of Escherichia coli O78 strains. FEMS Microbiol Lett 222:199–203
Ansari MM, Renshaw HW, Gates NL (1978) Colibacillosis in neonatal lambs: onset of diarrheal disease and isolation and characterization of enterotoxigenic Escherichia coli from enteric and septicemic forms of the disease. Am J Vet Res 39:11–14
Babai R, Blum-Oehler G, Stern BE, Hacker J, Ron EZ (1997) Virulence patterns from septicemic Escherichia coli O78 strains. FEMS Microbiol Lett 149:99–105
Babai R, Stern BE, Hacker J, Ron EZ (2000) New fimbrial gene cluster of S-fimbrial adhesin family. Infect Immun 68:5901–5907
Bauchart P, Germon P, Bree A, Oswald E, Hacker J, Dobrindt U (2010) Pathogenomic comparison of human extraintestinal and avian pathogenic Escherichia coli–search for factors involved in host specificity or zoonotic potential. Microb Pathog 49:105–115
Binns MM, Davies DL, Hardy KG (1979) Cloned fragments of the plasmid ColV, I-K94 specifying virulence and serum resistance. Nature 279:778–781
Binns MM, Mayden J, Levine RP (1982) Further characterization of complement resistance conferred on Escherichia coli by the plasmid genes traT of R100 and iss of ColV, I-K94. Infect Immun 35:654–659
Biran D and Ron EZ (2017) Unpublished results
Buckles EL, Wang X, Lane MC, Lockatell CV, Johnson DE, Rasko DA, Mobley HL, Donnenberg MS (2009) Role of the K2 capsule in Escherichia coli urinary tract infection and serum resistance. J Infect Dis 199:1689–1697
Buhler T, Hoschutzky H, Jann K (1991) Analysis of colonization factor antigen I, an adhesin of enterotoxigenic Escherichia coli O78:H11: fimbrial morphology and location of the receptor-binding site. Infect Immun 59:3876–3882
Caboni M, Pedron T, Rossi O, Goulding D, Pickard D, Citiulo F, MacLennan CA, Dougan G, Thomson NR, Saul A et al (2015) An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei. PLoS Pathog 11:e1004749
Cheney CP, Boedeker EC (1983) Adherence of an enterotoxigenic Escherichia coli strain, serotype O78:H11, to purified human intestinal brush borders. Infect Immun 39:1280–1284
Cheng D, Zhu S, Su Z, Zuo W, Lu H (2012) Prevalence and isoforms of the pathogenicity island ETT2 among Escherichia coli isolates from colibacillosis in pigs and mastitis in cows. Curr Microbiol 64:43–49
Cordoni G, Woodward MJ, Wu H, Alanazi M, Wallis T, La Ragione RM (2016) Comparative genomics of European avian pathogenic E. coli (APEC). BMC Genom 17:960
Czirok E, Milch H, Madar J, Semjen G (1977) Characterization of Escherichia coli serogroups causing meningitis, sepsis and enteritis. I. Serological properties and animal pathogenicity of O18, O78 and O83 isolates. Acta Microbiol Acad Scientiarum Hung 24:115–126
De Rycke J, Oswald E (2001) Cytolethal distending toxin (CDT): a bacterial weapon to control host cell proliferation? FEMS Microbiol Lett 203:141–148
Dho-Moulin M, Fairbrother JM (1999) Avian pathogenic Escherichia coli (APEC). Vet Res 30:299–316
Dobrindt U, Blum-Oehler G, Hartsch T, Gottschalk G, Ron EZ, Funfstuck R, Hacker J (2001) S-Fimbria-encoding determinant sfa(I) is located on pathogenicity island III(536) of uropathogenic Escherichia coli strain 536. Infect Immun 69:4248–4256
Dozois CM, Clement S, Desautels C, Oswald E, Fairbrother JM (1997) Expression of P, S, and F1C adhesins by cytotoxic necrotizing factor 1-producing Escherichia coli from septicemic and diarrheic pigs. FEMS Microbiol Lett 152:307–312
Duff JP, Hunt BW (1989) Lambs die from porcine E coli. Vet Rec 125:404
Dziva F, Hauser H, Connor TR, van Diemen PM, Prescott G, Langridge GC, Eckert S, Chaudhuri RR, Ewers C, Mellata M et al (2013) Sequencing and functional annotation of avian pathogenic Escherichia coli serogroup O78 strains reveal the evolution of E. coli lineages pathogenic for poultry via distinct mechanisms. Infect Immun 81:838–849
Ejrnaes K (2011) Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull 58:B4187
Ena J, Arjona F, Martinez-Peinado C, Lopez-Perezagua Mdel M, Amador C (2006) Epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Urology 68:1169–1174
Ewers C, Li G, Wilking H, Kiessling S, Alt K, Antao EM, Laturnus C, Diehl I, Glodde S, Homeier T et al (2007) Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they? Int J Med Microbiol: IJMM 297:163–176
Foxman B (2010) The epidemiology of urinary tract infection. Nat Rev. Urol 7:653–660
Foxman B (2014) Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 28:1–13
Goller CC, Seed PC (2010) Revisiting the Escherichia coli polysaccharide capsule as a virulence factor during urinary tract infection: contribution to intracellular biofilm development. Virulence 1:333–337
Gophna U, Oelschlaeger TA, Hacker J, Ron EZ (2001) Yersinia HPI in septicemic Escherichia coli strains isolated from diverse hosts. FEMS Microbiol Lett 196:57–60
Grozdanov L, Zahringer U, Blum-Oehler G, Brade L, Henne A, Knirel YA, Schombel U, Schulze J, Sonnenborn U, Gottschalk G et al (2002) A single nucleotide exchange in the wzy gene is responsible for the semirough O6 lipopolysaccharide phenotype and serum sensitivity of Escherichia coli strain Nissle 1917. J Bacteriol 184:5912–5925
Hacker J, Schmidt G, Hughes C, Knapp S, Marget M, Goebel W (1985) Cloning and characterization of genes involved in production of mannose-resistant, neuraminidase-susceptible (X) fimbriae from a uropathogenic O6:K15:H31 Escherichia coli strain. Infect Immun 47:434–440
Hafez M, Hayes K, Goldrick M, Warhurst G, Grencis R, Roberts IS (2009) The K5 capsule of Escherichia coli strain Nissle 1917 is important in mediating interactions with intestinal epithelial cells and chemokine induction. Infect Immun 77:2995–3003
Hammond SM (1992) Inhibitors of lipopolysaccharide biosynthesis impair the virulence potential of Escherichia coli. FEMS Microbiol Lett 100:293–297
Hartleib S, Prager R, Hedenstrom I, Lofdahl S, Tschape H (2003) Prevalence of the new, SPI1-like, pathogenicity island ETT2 among Escherichia coli. Int J Med Microbiol: IJMM 292:487–493
Holden NJ, Gally DL (2004) Switches, cross-talk and memory in Escherichia coli adherence. J Med Microbiol 53:585–593
Horne SM, Pfaff-McDonough SJ, Giddings CW, Nolan LK (2000) Cloning and sequencing of the iss gene from a virulent avian Escherichia coli. Avian Dis 44:179–184
Hu Y, Huang H, Cheng X, Shu X, White AP, Stavrinides J, Koster W, Zhu G, Zhao Z, Wang Y (2017) A global survey of bacterial type III secretion systems and their effectors. Environ Microbiol
Huja S, Oren Y, Biran D, Meyer S, Dobrindt U, Bernhard J, Becher D, Hecker M, Sorek R, Ron EZ (2014). Fur is the master regulator of the extraintestinal pathogenic Escherichia coli response to serum. MBio 5
Huja S, Oren Y, Trost E, Brzuszkiewicz E, Biran D, Blom J, Goesmann A, Gottschalk G, Hacker J, Ron EZ et al (2015) Genomic avenue to avian colisepticemia. MBio 6
Ideses D, Gophna U, Paitan Y, Chaudhuri RR, Pallen MJ, Ron EZ (2005) A degenerate type III secretion system from septicemic Escherichia coli contributes to pathogenesis. J Bacteriol 187:8164–8171
Jacobsen SM, Stickler DJ, Mobley HL, Shirtliff ME (2008) Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis. Clin Microbiol Rev 21:26–59
Johnson TJ, Wannemuehler YM, Nolan LK (2008) Evolution of the iss gene in Escherichia coli. Appl Environ Microbiol 74:2360–2369
Kalita A, Hu J, Torres AG (2014) Recent advances in adherence and invasion of pathogenic Escherichia coli. Curr Opin Infect Dis 27:459–464
Khan AS, Kniep B, Oelschlaeger TA, Van Die I, Korhonen T, Hacker J (2000) Receptor structure for F1C fimbriae of uropathogenic Escherichia coli. Infect Immun 68:3541–3547
Kim KJ, Elliott SJ, Di Cello F, Stins MF, Kim KS (2003) The K1 capsule modulates trafficking of E. coli-containing vacuoles and enhances intracellular bacterial survival in human brain microvascular endothelial cells. Cell Microbiol 5:245–252
Kjelstrup CK, Arnesen LP, Granquist EG, L’Abee-Lund TM (2013) Characterization of Escherichia coli O78 from an outbreak of septicemia in lambs in Norway. Vet Microbiol 166:276–280
Korhonen TK, Vaisanen V, Saxen H, Hultberg H, Svenson SB (1982) P-antigen-recognizing fimbriae from human uropathogenic Escherichia coli strains. Infect Immun 37:286–291
Krishnan S, Chang AC, Hodges J, Couraud PO, Romero IA, Weksler B, Nicholson BA, Nolan LK, Prasadarao NV (2015) Serotype O18 avian pathogenic and neonatal meningitis Escherichia coli strains employ similar pathogenic strategies for the onset of meningitis. Virulence 6:777–786
Kusecek B, Wloch H, Mercer A, Vaisanen V, Pluschke G, Korhonen T, Achtman M (1984) Lipopolysaccharide, capsule, and fimbriae as virulence factors among O1, O7, O16, O18, or O75 and K1, K5, or K100 Escherichia coli. Infect Immun 43:368–379
Lane MC, Mobley HL (2007) Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney Int 72:19–25
Lund B, Marklund BI, Stromberg N, Lindberg F, Karlsson KA, Normark S (1988) Uropathogenic Escherichia coli can express serologically identical pili of different receptor binding specificities. Mol Microbiol 2:255–263
Lynne AM, Skyberg JA, Logue CM, Nolan LK (2007) Detection of Iss and Bor on the surface of Escherichia coli. J Appl Microbiol 102:660–666
Maluta RP, Logue CM, Casas MR, Meng T, Guastalli EA, Rojas TC, Montelli AC, Sadatsune T, de Carvalho Ramos M, Nolan LK et al (2014) Overlapped sequence types (STs) and serogroups of avian pathogenic (APEC) and human extra-intestinal pathogenic (ExPEC) Escherichia coli isolated in Brazil. PLoS ONE 9:e105016
Manges AR (2016) Escherichia coli and urinary tract infections: the role of poultry-meat. Clin Microbiol Infect: the Official Publ Eur Soc Clin Microbiol Infect Dis 22:122–129
Mangiamele P, Nicholson B, Wannemuehler Y, Seemann T, Logue CM, Li G, Tivendale KA, Nolan LK (2013) Complete genome sequence of the avian pathogenic Escherichia coli strain APEC O78. Genome Announcements 1:e0002613
Marrs CF, Zhang L, Foxman B (2005) Escherichia coli mediated urinary tract infections: are there distinct uropathogenic E. coli (UPEC) pathotypes? FEMS Microbiol Lett 252:183–190
Mellata M, Touchman JW, Curtiss R (2009) Full sequence and comparative analysis of the plasmid pAPEC-1 of avian pathogenic E. coli chi7122 (O78:K80:H9). PLoS ONE 4:e4232
Milch H, Czirok E, Madar J, Semjen G (1977) Characterization of Escherichia coli serogroups causing meningitis, sepsis and enteritis. II. Classification of Escherichia coli O78 strains by phage sensitivity, colicin type and antibiotic resistance. Acta Microbiol Acad Scientiarum Hung 24:127–137
Milch H, Nikolnikov S, Czirok E (1984) Escherichia coli Col V plasmids and their role in pathogenicity. Acta Microbiol Hung 31:117–125
Moch T, Hoschutzky H, Hacker J, Kroncke KD, Jann K (1987) Isolation and characterization of the alpha-sialyl-beta-2,3-galactosyl-specific adhesin from fimbriated Escherichia coli. Proc Natl Acad Sci USA 84:3462–3466
Mokady D, Gophna U, Ron EZ (2005a) Extensive gene diversity in septicemic Escherichia coli strains. J Clin Microbiol 43:66–73
Mokady D, Gophna U, Ron EZ (2005b) Virulence factors of septicemic Escherichia coli strains. Int J Med Microbiol: IJMM 295:455–462
Nicholson BA, Wannemuehler YM, Logue CM, Li G, Nolan LK (2016) Complete Genome Sequence of the Avian-Pathogenic Escherichia coli Strain APEC O18. Genome Announcements 4
Nolan LK, Giddings CW, Horne SM, Doetkott C, Gibbs PS, Wooley RE, Foley SL (2002) Complement resistance, as determined by viable count and flow cytometric methods, and its association with the presence of iss and the virulence of avian Escherichia coli. Avian Dis 46:386–392
Nolan LK, Horne SM, Giddings CW, Foley SL, Johnson TJ, Lynne AM, Skyberg J (2003) Resistance to serum complement, iss, and virulence of avian Escherichia coli. Vet Res Commun 27:101–110
Otto A, Biran D, Sura T, Becher D, Ron EZ (2016) Proteomics of septicemic Escherichia coli. Proteomics. Clin Appl 10:1020–1024
Parkkinen J, Rogers GN, Korhonen T, Dahr W, Finne J (1986) Identification of the O-linked sialyloligosaccharides of glycophorin A as the erythrocyte receptors for S-fimbriated Escherichia coli. Infect Immun 54:37–42
Peres SY, Marches O, Daigle F, Nougayrede JP, Herault F, Tasca C, De Rycke J, Oswald E (1997) A new cytolethal distending toxin (CDT) from Escherichia coli producing CNF2 blocks HeLa cell division in G2/M phase. Mol Microbiol 24:1095–1107
Phan MD, Peters KM, Sarkar S, Lukowski SW, Allsopp LP, Gomes Moriel D, Achard ME, Totsika M, Marshall VM, Upton M et al (2013) The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone. PLoS Genet 9:e1003834
Ren CP, Chaudhuri RR, Fivian A, Bailey CM, Antonio M, Barnes WM, Pallen MJ (2004) The ETT2 gene cluster, encoding a second type III secretion system from Escherichia coli, is present in the majority of strains but has undergone widespread mutational attrition. J Bacteriol 186:3547–3560
Rodriguez-Siek KE, Giddings CW, Doetkott C, Johnson TJ, Nolan LK (2005) Characterizing the APEC pathotype. Vet Res 36:241–256
Ron EZ (2006) Host specificity of septicemic Escherichia coli: human and avian pathogens. Curr Opin Microbiol 9:28–32
Ron EZ (2010) Distribution and evolution of virulence factors in septicemic Escherichia coli. Int J Med Microbiol: IJMM 300:367–370
Sarkar S, Ulett GC, Totsika M, Phan MD, Schembri MA (2014) Role of capsule and O antigen in the virulence of uropathogenic Escherichia coli. PLoS ONE 9:e94786
Shifrin Y, Peleg A, Ilan O, Nadler C, Kobi S, Baruch K, Yerushalmi G, Berdichevsky T, Altuvia S, Elgrably-Weiss M et al (2008) Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule. J Bacteriol 190:5063–5074
Shulman A, Yair Y, Biran D, Sura T, Otto A, Gophna U, Becher D, Hecker M. Ron EZ (2018) The Escherichia coli type III secretion system 2 has a global effect on cell surface. mBio 01070–18
Sola-Gines M, Cameron-Veas K, Badiola I, Dolz R, Majo N, Dahbi G, Viso S, Mora A, Blanco J, Piedra-Carrasco N et al (2015) Diversity of multi-drug resistant avian pathogenic Escherichia coli (APEC) causing outbreaks of colibacillosis in broilers during 2012 in Spain. PLoS ONE 10:e0143191
Stromberg N, Marklund BI, Lund B, Ilver D, Hamers A, Gaastra W, Karlsson KA, Normark S (1990) Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1-4Gal-containing isoreceptors. The EMBO J 9:2001–2010
Taieb F, Petit C, Nougayrede JP, Oswald E (2016) The enterobacterial genotoxins: Cytolethal distending toxin and colibactin. EcoSal Plus 7
Thomassin JL, Lee MJ, Brannon JR, Sheppard DC, Gruenheid S, Le Moual H (2013) Both group 4 capsule and lipopolysaccharide O-antigen contribute to enteropathogenic Escherichia coli resistance to human alpha-defensin 5. PLoS ONE 8:e82475
Tivendale KA, Logue CM, Kariyawasam S, Jordan D, Hussein A, Li G, Wannemuehler Y, Nolan LK (2010) Avian-pathogenic Escherichia coli strains are similar to neonatal meningitis E. coli strains and are able to cause meningitis in the rat model of human disease. Infect Immun 78:3412–3419
van Die I, Kramer C, Hacker J, Bergmans H, Jongen W, Hoekstra W (1991) Nucleotide sequence of the genes coding for minor fimbrial subunits of the F1C fimbriae of Escherichia coli. Res Microbiol 142:653–658
Wang S, Liu X, Xu X, Yang D, Wang D, Han X, Shi Y, Tian M, Ding C, Peng D et al (2016a) Escherichia coli type III secretion system 2 ATPase EivC Is Involved in the motility and virulence of avian pathogenic Escherichia coli. Front Microbiol 7:1387
Wang S, Liu X, Xu X, Zhao Y, Yang D, Han X, Tian M, Ding C, Peng D, Yu S (2016b) Escherichia coli type III secretion system 2 (ETT2) is widely distributed in avian pathogenic Escherichia coli isolates from Eastern China. Epidemiol Infect 144:2824–2830
Waters VL, Crosa JH (1991) Colicin V virulence plasmids. Microbiol Rev 55:437–450
Weinberg ED (2009) Iron availability and infection. Biochem Biophys Acta 1790:600–605
Whitfield C, Roberts IS (1999) Structure, assembly and regulation of expression of capsules in Escherichia coli. Mol Microbiol 31:1307–1319
Wijetunge DS, Gongati S, DebRoy C, Kim KS, Couraud PO, Romero IA, Weksler B, Kariyawasam S (2015a) Characterizing the pathotype of neonatal meningitis causing Escherichia coli (NMEC). BMC Microbiol 15:211
Wijetunge DS, Karunathilake KH, Chaudhari A, Katani R, Dudley EG, Kapur V, DebRoy C, Kariyawasam S (2014) Complete nucleotide sequence of pRS218, a large virulence plasmid, that augments pathogenic potential of meningitis-associated Escherichia coli strain RS218. BMC Microbiol 14:203
Wijetunge DS, Katani R, Kapur V, Kariyawasam S (2015b) Complete genome sequence of Escherichia coli strain RS218 (O18:H7:K1), associated with neonatal meningitis. Genome Announcements 3
Yerushalmi Z, Smorodinsky NI, Naveh MW, Ron EZ (1990) Adherence pili of avian strains of Escherichia coli O78. Infect Immun 58:1129–1131
Zhang L, Chaudhuri RR, Constantinidou C, Hobman JL, Patel MD, Jones AC, Sarti D, Roe AJ, Vlisidou I, Shaw RK et al (2004) Regulators encoded in the Escherichia coli type III secretion system 2 gene cluster influence expression of genes within the locus for enterocyte effacement in enterohemorrhagic E. coli O157:H7. Infect Immun 72:7282–7293
Zhang L, Foxman B (2003) Molecular epidemiology of Escherichia coli mediated urinary tract infections. Front Biosci: A J virtual Libr 8:e235–e244
Zhu Ge X, Jiang J, Pan Z, Hu L, Wang S, Wang H, Leung FC, Dai J, Fan H (2014) Comparative genomic analysis shows that avian pathogenic Escherichia coli isolate IMT5155 (O2:K1:H5; ST complex 95, ST140) shares close relationship with ST95 APEC O1:K1 and human ExPEC O18:K1 strains. PLoS ONE 9:e112048
Acknowledgements
This project was supported by a DIP grant from the German-Israeli Project Cooperation (RO 2612/1-1), by the EC Network of Excellence Euro-PathoGenomics (CEE LSHB-CT-2005-512061), by the ERA-NET Pathogenomics project COLIRISK, by the JPIAMR (Joint Programming Initiative on Antimicrobial Resistance), by the Infect Era EC ERA-NET and by the Israeli Ministry of Health.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Biran, D., Ron, E.Z. (2018). Extraintestinal Pathogenic Escherichia coli. In: Frankel, G., Ron, E. (eds) Escherichia coli, a Versatile Pathogen. Current Topics in Microbiology and Immunology, vol 416. Springer, Cham. https://doi.org/10.1007/82_2018_108
Download citation
DOI: https://doi.org/10.1007/82_2018_108
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-99663-9
Online ISBN: 978-3-319-99664-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)