*3.5.1 Adhesins and invasins*

Once a bacterium reaches the host surface, in order to colonize, it must adhere to host cells. For this purpose bacteria have different fimbrial and afimbrial adhesins. Fimbrial adhesins are rod-shaped protein structures, which consists primarily of an ordered array of single protein subunits, which build a long cylindrical structure. At the top, there are proteins, adhesins, which mediate the adherence to the host's molecules. A fimbrial adhesin is thus a structure that extends outward from the bacterial surface and establishes the contact between the bacterial surface and the surface of the host cells. Afimbrial adhesins are surface proteins important for tighter binding of bacteria to host cells. Some bacteria have evolved mechanisms for entering nonphagocytic host cells. Bacterial surface proteins that provoke actin rearrangements and thereby incite the phagocytic ingestion of the bacterium by host cells are called invasins [36]. The most known *E. coli* adhesins and invasins are presented in **Table 2**.

#### **Figure 8.**

*Classification of pathogenic E. coli, based on Roy et al. [33]. The IPEC are also designated as diarrheagenic E. coli (DEC)—Although not all of the subtypes in this group necessarily cause diarrhea. STEC that cause hemorrhagic colitis and/or the hemolytic uremic syndrome are called EHEC—For enterohemorrhagic E. coli. Among ExPEC also strains associated with pneumonia, skin and soft-tissues, and infections of many other extraintestinal anatomic sites are present, though they are not yet established as separate pathotypes.*

**11**

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*

Type 1 fimbriae (Fim) *fimH* P fimbriae (Pap/Prf) *papC*, *papG* S/F1C fimbriae (Sfa/Foc) *sfa/focDE* N-Acetyl-d-glucosamine-specific fimbriae (Gaf) *gafD* M-Agglutinin (Bma) *bmaE* Bifunctional enterobactin receptor/adhesin (Iha) *iha* Afimbrial adhesin (Afa) *afa/draBC* Invasion of brain endothelium (IbeA) *ibeA* Colonization factor antigen I (CFA/I) *cfaB* Bundle-forming pili (BFP) *bfpA* Intimin *eaeA* Aggregative adherence fimbriae (AAF/I) *aaf/I*

*3.5.2 Iron acquisition mechanisms*

**Table 2.**

iron uptake systems are presented in **Table 3**.

*Typical adhesins and invasins of pathogenic E. coli strains.*

to evade host immune response are presented in **Table 4**.

*3.5.3 Systems to evade host immune response*

Iron is essential for bacterial growth, but iron concentrations in nature are generally quite low, particularly low in host organism. To survive in the host organism, bacteria must have some mechanisms for acquiring iron. The best studied type of bacterial iron acquisition is the siderophores. These are low-molecular-weight compounds that chelate iron with very high affinity [36]. The most known *E. coli*

**Adhesin/invasin Most commonly tested virulence** 

**(associated) genes**

The healthy host usually has multilayered defenses that prevent the establishment of bacterial infection. Among the most effective of these defenses is the immune response. However, bacteria have evolved systems to avoid, subvert, or circumvent innate host defenses and to evade acquired specific immune responses of the host [34]. A capsule is a loose, relatively unstructured network of polymers that covers the surface of a bacterium. The role of capsules in bacterial virulence is to protect bacteria from the host's inflammatory response [36]. Further, increased serum resistance is often found among pathogenic bacteria, especially those associated with systemic infections [36]. Serum resistance is the ability to prevent complement activation on the bacterial cell surface and to inhibit insertion of the membrane attack complex into the bacterial membrane [34]. The feature is often based on the modifications in lipopolysaccharide (LPS), which can be of two types: either attachment of sialic acid to LPS O antigen or changes in the LPS O antigen side chain [36]. However, other proteins can also be implicated in increased serum resistance; for example, the TraT protein of the surface exclusion complex involved in conjugation [37]. Another important protein of pathogenic *E. coli* is the Toll/ interleukin-1 receptor domain-containing protein (Tcp) that interferes with the TLR signaling system of the innate immunity [38]. The most known *E. coli* systems

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*


#### **Table 2.**

*The Universe of Escherichia coli*

*E. coli* pathotypes.

defenses [35].

*3.5.1 Adhesins and invasins*

presented in **Table 2**.

pathogenic *E. coli* (IPEC), associated with infections of the gastrointestinal tract, and the extraintestinal pathogenic *E. coli* (ExPEC), associated with infections of extraintestinal anatomic sites [7]. The medical diversity of this species is nicely exhibited by its classification of pathogenic *E. coli* (**Figure 8**), the so-called

The versatility of pathogenic *E. coli* strains depends on their genetic makeup, on the presence of so-called virulence genes, and possession of such genes distinguishes pathogenic from nonpathogenic bacteria [34]. Virulence factors help bacteria to (1) invade the host, (2) cause disease, and (3) evade host

*Classification of pathogenic E. coli, based on Roy et al. [33]. The IPEC are also designated as diarrheagenic E. coli (DEC)—Although not all of the subtypes in this group necessarily cause diarrhea. STEC that cause hemorrhagic colitis and/or the hemolytic uremic syndrome are called EHEC—For enterohemorrhagic E. coli. Among ExPEC also strains associated with pneumonia, skin and soft-tissues, and infections of many other extraintestinal anatomic sites are present, though they are not yet established* 

Once a bacterium reaches the host surface, in order to colonize, it must adhere to host cells. For this purpose bacteria have different fimbrial and afimbrial adhesins. Fimbrial adhesins are rod-shaped protein structures, which consists primarily of an ordered array of single protein subunits, which build a long cylindrical structure. At the top, there are proteins, adhesins, which mediate the adherence to the host's molecules. A fimbrial adhesin is thus a structure that extends outward from the bacterial surface and establishes the contact between the bacterial surface and the surface of the host cells. Afimbrial adhesins are surface proteins important for tighter binding of bacteria to host cells. Some bacteria have evolved mechanisms for entering nonphagocytic host cells. Bacterial surface proteins that provoke actin rearrangements and thereby incite the phagocytic ingestion of the bacterium by host cells are called invasins [36]. The most known *E. coli* adhesins and invasins are

**10**

**Figure 8.**

*as separate pathotypes.*

*Typical adhesins and invasins of pathogenic E. coli strains.*

#### *3.5.2 Iron acquisition mechanisms*

Iron is essential for bacterial growth, but iron concentrations in nature are generally quite low, particularly low in host organism. To survive in the host organism, bacteria must have some mechanisms for acquiring iron. The best studied type of bacterial iron acquisition is the siderophores. These are low-molecular-weight compounds that chelate iron with very high affinity [36]. The most known *E. coli* iron uptake systems are presented in **Table 3**.

#### *3.5.3 Systems to evade host immune response*

The healthy host usually has multilayered defenses that prevent the establishment of bacterial infection. Among the most effective of these defenses is the immune response. However, bacteria have evolved systems to avoid, subvert, or circumvent innate host defenses and to evade acquired specific immune responses of the host [34]. A capsule is a loose, relatively unstructured network of polymers that covers the surface of a bacterium. The role of capsules in bacterial virulence is to protect bacteria from the host's inflammatory response [36]. Further, increased serum resistance is often found among pathogenic bacteria, especially those associated with systemic infections [36]. Serum resistance is the ability to prevent complement activation on the bacterial cell surface and to inhibit insertion of the membrane attack complex into the bacterial membrane [34]. The feature is often based on the modifications in lipopolysaccharide (LPS), which can be of two types: either attachment of sialic acid to LPS O antigen or changes in the LPS O antigen side chain [36]. However, other proteins can also be implicated in increased serum resistance; for example, the TraT protein of the surface exclusion complex involved in conjugation [37]. Another important protein of pathogenic *E. coli* is the Toll/ interleukin-1 receptor domain-containing protein (Tcp) that interferes with the TLR signaling system of the innate immunity [38]. The most known *E. coli* systems to evade host immune response are presented in **Table 4**.


#### **Table 3.**

*Typical iron uptake systems of pathogenic E. coli strains.*


#### **Table 4.**

*Typical host immunity evading systems of pathogenic E. coli strains.*

### *3.5.4 Toxins*

Toxins are the virulence factors that damage the host. Exotoxins are toxic bacterial proteins that are excreted into the medium by growing bacteria or localized in the bacterial cytoplasm or periplasm and released during bacterial lysis. Exotoxins vary considerably in their activities and the target host cell types [36]. The most known *E. coli* toxins (exotoxins) are presented in **Table 5**.


**13**

**Figure 9.**

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*

**3.6 The antibiotic-resistant** *E. coli*

spread in the population [36].

**3.7 The bacteriocinogenic** *E. coli*

However, *E. coli* possess also an endotoxin, namely, the lipopolysaccharide, which is an integral component of the outer membrane of Gram-negative bacteria. The lipid portion (lipid A) is embedded in the outer membrane, with the core and O antigen portions extending outward from the bacterial surface. Lipid A is the toxic portion of the molecule, and it exerts its effects only when bacteria are lysed. The toxicity of lipid A resides primarily in its ability to activate, complement, and

Antibiotics are low-molecular-weight compounds that kill or inhibit growth of bacteria [36]. Antibiotic treatment is one of the main approaches of modern medicine to combat bacterial infections, including also *E. coli* infections [39]. However, bacteria evolved different mechanisms that confer resistances to antibiotics. Resistant bacteria are able to either (i) modify/degrade the antibiotic, (ii) actively transport the antibiotic out of the cell or prevent its intake, (iii) sequester the antibiotic by special proteins, or (iv) modify, bypass, or protect the target [40]. The emergence, spread, and persistence of resistant and even multidrug-resistant (MDR) bacteria or "superbugs", also among *E. coli*, are now posing a serious global health threat of growing concern [39]. The antimicrobial resistance surveillance data of European Centre for Disease Prevention and Control (ECDC) also showed the increase in antibiotic resistance among invasive *E. coli* isolates (**Figure 9**).

The mechanisms of resistance to antibiotics are encoded in resistance genes. A

As many of the resistance genes are encoded on conjugative plasmids or conjugative transposons, they are easily transferred between different bacteria and hence

Bacteriocins are ribosomally synthesized, proteinaceous substances that inhibit the growth of closely related species through numerous mechanisms [51].

*Prevalence of invasive E. coli isolates with antimicrobial resistance to aminopenicillins, fluoroquinolones, third-generation cephalosporins, aminoglycosides, and carbapenems—the population weighted mean EU/EEA is shown. The prevalence of antimicrobial resistance to carbapenems in 2009 and 2011 was 0%, in 2012 <0.1%,* 

*in 2013 and 2015 0.2%, and in 2014, 2016, and 2017 0.1% [41–49].*

list of typical *E. coli* resistance genes is given in **Table 6**.

stimulate the release of bioactive host proteins, such as cytokines [36].

#### **Table 5.**

*Typical toxins (exotoxins) of pathogenic E. coli strains.*

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*

*The Universe of Escherichia coli*

protease (Hbp)—in humans

**12**

**Table 5.**

*3.5.4 Toxins*

**Table 4.**

**Table 3.**

containing protein Tcp)

Toxins are the virulence factors that damage the host. Exotoxins are toxic bacterial proteins that are excreted into the medium by growing bacteria or localized in the bacterial cytoplasm or periplasm and released during bacterial lysis. Exotoxins vary considerably in their activities and the target host cell types [36]. The most

**Toxins Most commonly tested virulence** 

**Host immunity evading system Most commonly tested virulence** 

**Iron uptake system Most commonly tested virulence** 

Group II capsule including K1 and K5 capsules *kpsMT II* Conjugal transfer surface exclusion protein (TraT) *traT*

Aerobactin (Iuc) *iucD*, *iutA* Yersiniabactin (Ybt) *fyuA*, *irp2* Salmochelin (Iro) *iroCD*, *iroN* Siderophore receptor IreA *ireA*

Temperature sensitive hemagglutinin (Tsh)—in birds, Hemoglobin

*Typical iron uptake systems of pathogenic E. coli strains.*

Periplasmic iron binding protein (SitA) *sitA* Ferrichrome-iron receptor (Fhu) *fhuA*

Increased serum survival (Iss) *iss* Suppression of innate immunity (Toll/interleukin-1 receptor domain-

Outer membrane protease T (OmpT) *ompT*, *APEC-ompT*

**(associated) genes**

**(associated) genes**

*tsh*, *hbp*

*tcpC*

**(associated) genes**

known *E. coli* toxins (exotoxins) are presented in **Table 5**.

alpha-Hemolysin (HlyA) *hlyA* Cytotoxic necrotizing factor 1 (CNF-1) *cnf1* Cytolethal distending toxin IV (CDT 1) *cdtB* Uropathogenic specific protein (Usp) *usp* Colibactin (Clb) *clbAQ* Serine protease autotransporters Sat, Pic *sat*, *picU* Heat-stable toxins (STa, STb) *stIa/stIb* Heat-labile toxin I (LTI), heat-labile toxin II (LTII) *eltI*, *eltIIa* Shiga toxin 1 (Stx1), Shiga toxin 2 (Stx2) *stxI*, *stxII* EHEC hemolysin (Ehx) *ehxA* Low-MW heat-stable toxin (EAST1) *astA*

*Typical toxins (exotoxins) of pathogenic E. coli strains.*

*Typical host immunity evading systems of pathogenic E. coli strains.*

However, *E. coli* possess also an endotoxin, namely, the lipopolysaccharide, which is an integral component of the outer membrane of Gram-negative bacteria. The lipid portion (lipid A) is embedded in the outer membrane, with the core and O antigen portions extending outward from the bacterial surface. Lipid A is the toxic portion of the molecule, and it exerts its effects only when bacteria are lysed. The toxicity of lipid A resides primarily in its ability to activate, complement, and stimulate the release of bioactive host proteins, such as cytokines [36].

#### **3.6 The antibiotic-resistant** *E. coli*

Antibiotics are low-molecular-weight compounds that kill or inhibit growth of bacteria [36]. Antibiotic treatment is one of the main approaches of modern medicine to combat bacterial infections, including also *E. coli* infections [39]. However, bacteria evolved different mechanisms that confer resistances to antibiotics. Resistant bacteria are able to either (i) modify/degrade the antibiotic, (ii) actively transport the antibiotic out of the cell or prevent its intake, (iii) sequester the antibiotic by special proteins, or (iv) modify, bypass, or protect the target [40]. The emergence, spread, and persistence of resistant and even multidrug-resistant (MDR) bacteria or "superbugs", also among *E. coli*, are now posing a serious global health threat of growing concern [39]. The antimicrobial resistance surveillance data of European Centre for Disease Prevention and Control (ECDC) also showed the increase in antibiotic resistance among invasive *E. coli* isolates (**Figure 9**).

The mechanisms of resistance to antibiotics are encoded in resistance genes. A list of typical *E. coli* resistance genes is given in **Table 6**.

As many of the resistance genes are encoded on conjugative plasmids or conjugative transposons, they are easily transferred between different bacteria and hence spread in the population [36].

#### **3.7 The bacteriocinogenic** *E. coli*

Bacteriocins are ribosomally synthesized, proteinaceous substances that inhibit the growth of closely related species through numerous mechanisms [51].

#### **Figure 9.**

*Prevalence of invasive E. coli isolates with antimicrobial resistance to aminopenicillins, fluoroquinolones, third-generation cephalosporins, aminoglycosides, and carbapenems—the population weighted mean EU/EEA is shown. The prevalence of antimicrobial resistance to carbapenems in 2009 and 2011 was 0%, in 2012 <0.1%, in 2013 and 2015 0.2%, and in 2014, 2016, and 2017 0.1% [41–49].*


*STR, streptomycin; KAN, kanamycin; GEN, gentamicin; AMP, ampicillin; AMC, amoxicillin/clavulanic acid; CRO, ceftriaxone; FOX, cefoxitin; TIO, ceftiofur; FIS, sulfisoxazole; SXT, trimethoprim/sulfamethoxazole; AZM, azithromycin; CHL, chloramphenicol; NAL, nalidixic acid; CIP, ciprofloxacin; TET, tetracycline [50].*

#### **Table 6.**

*Typical E. coli resistance genes.*

They are a heterogeneous group of particles with different morphological and biochemical entities. They range from a simple protein to a high molecular weight complex [52]. The bacteriocins with molecular masses below 10 kDa are designated as microcins [53]. Bacteriocins are potent toxins that are usually produced during stressful conditions and result in the rapid elimination of neighboring bacterial cells that are not immune or resistant to their effect. The killing is exhibited after adsorption to specific receptors located on the external surface of sensitive bacteria, by one of the three primary mechanisms: forming channels in the cytoplasmic membrane, degrading cellular DNA/RNA, or inhibiting protein synthesis. Because of their narrow range of activity, it has been proposed that the primary role of bacteriocins is to mediate intraspecific, or population level, interactions [54]. The genetic determinants of most of the bacteriocins are located on the plasmids, apart from few, which are chromosomally encoded [52]. Bacteriocins of *E. coli* are usually called colicins. A relatively high frequency of colicin-encoding plasmids is found in isolates of pathogenic *E. coli* [55], for example, ~80% of O157:H7 enterohemorrhagic *E. coli* strains studied by Bradley and Howard were colicinogenic [56]. Especially microcins have been associated with pathogenic strains [54]. In a collection of *E. coli* strains isolated from skin and soft-tissue infections, 55% of strains possessed microcin M, and 43% possessed microcin H47 [57]. Further, colicin insensitivity among these strains correlated with a higher prevalence of extraintestinal virulence factors [58]. Typical *E. coli* bacteriocins, their receptors, translocation systems, and mode of action are given in **Table 7**.

**15**

**3.8 The probiotic** *E. coli*

**Table 7.**

mortality [62].

killed [65, 66].

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Probiotic bacteria act via a variety of means, including modulation of immune function, production of organic acids and antimicrobial compounds, interaction with resident microbiota, interfacing with the host, improving the gut barrier integrity, and enzyme formation [61]. Several *E. coli* strains were recognized as good and effective probiotics and are now used in drugs (see **Table 8**). The probiotic *E. coli* are applied to a variety of human conditions, including intestinal bowel diseases and diarrhea. Further it was shown that colonization of newborns led to reduced disease rates, lower incidence of allergies, and reduced

ColM FhuA Ton Inhibition of peptidoglycan synthesis

*E. coli* Nissle 1917 is nowadays often used as a reference strain or model microorganism in experimental biomedical studies, including recombinant manipulations of the strain in order to construct derivatives with novel properties [64]. One such example is the strain ŽP, which is a genetically modified Nissle 1917 possessing a bacterial conjugation-based "kill"-"anti-kill" antimicrobial system—a conjugative plasmid carrying the "kill" gene (colicin ColE7 activity gene) and a chromosomally encoded "anti-kill" gene (ColE7 immunity gene). Hence, in the process of conjugation, the conjugative plasmid transfers the "kill" gene into a recipient cell, where it is expressed and the recipient

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*

**Bacteriocin Receptor Translocation system Mode of action** ColA BtuB Tol Ion channel ColB FepA Ton Ion channel ColD FepA Ton Stops translation ColE1 BtuB Tol Ion channel

ColE2 BtuB Tol DNA-endonuclease ColE3 BtuB Tol rRNA-endonuclease ColE4 BtuB Tol rRNA-endonuclease ColE5 BtuB Tol Stops translation ColE6 BtuB Tol rRNA-endonuclease ColE7 BtuB Tol DNA-endonuclease ColE8-J BtuB Tol DNA-endonuclease

ColIa Cir Ton Ion channel ColIb Cir Ton Ion channel ColK Tsx Tol Ion channel

ColN OmpF Tol Ion channel ColS4 OmpW Tol Ion channel

*Typical E. coli bacteriocins, their receptor, translocation system, and mode of action [59, 60].*

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*


**Table 7.**

*The Universe of Escherichia coli*

They are a heterogeneous group of particles with different morphological and biochemical entities. They range from a simple protein to a high molecular weight complex [52]. The bacteriocins with molecular masses below 10 kDa are designated as microcins [53]. Bacteriocins are potent toxins that are usually produced during stressful conditions and result in the rapid elimination of neighboring bacterial cells that are not immune or resistant to their effect. The killing is exhibited after adsorption to specific receptors located on the external surface of sensitive bacteria, by one of the three primary mechanisms: forming channels in the cytoplasmic membrane, degrading cellular DNA/RNA, or inhibiting protein synthesis. Because of their narrow range of activity, it has been proposed that the primary role of bacteriocins is to mediate intraspecific, or population level, interactions [54]. The genetic determinants of most of the bacteriocins are located on the plasmids, apart from few, which are chromosomally encoded [52]. Bacteriocins of *E. coli* are usually called colicins. A relatively high frequency of colicin-encoding plasmids is found in isolates of pathogenic *E. coli* [55], for example, ~80% of O157:H7 enterohemorrhagic *E. coli* strains studied by Bradley and Howard were colicinogenic [56]. Especially microcins have been associated with pathogenic strains [54]. In a collection of *E. coli* strains isolated from skin and soft-tissue infections, 55% of strains possessed microcin M, and 43% possessed microcin H47 [57]. Further, colicin insensitivity among these strains correlated with a higher prevalence of extraintestinal virulence factors [58]. Typical *E. coli* bacteriocins, their receptors, translocation systems, and mode of action are

*azithromycin; CHL, chloramphenicol; NAL, nalidixic acid; CIP, ciprofloxacin; TET, tetracycline [50].*

*STR, streptomycin; KAN, kanamycin; GEN, gentamicin; AMP, ampicillin; AMC, amoxicillin/clavulanic acid; CRO, ceftriaxone; FOX, cefoxitin; TIO, ceftiofur; FIS, sulfisoxazole; SXT, trimethoprim/sulfamethoxazole; AZM,* 

**Resistance gene(s) Antibiotic class Resistance to**

*bla*CMY-2 β-Lactams AMC, AMP, CRO, FOX, TIO

*ampC* β-Lactams AMC, AMP, FOX

*sul1*, *sul2*, *sul3* Folate synthesis inhibitors FIS *dfrA1*, *dfrA5*, *dfrA12*, *dfrA17* Folate synthesis inhibitors SXT *mphA* Macrolides AZM *floR* Phenicols CHL *cmlA* Phenicols CHL *catA1*, *catB3* Phenicols CHL *qnrB2*, *qnrB6*, *qnrS2* Quinolones NAL, CIP *tet*(A), *tet*(B), *tet*(C), *tet*(D), *tet*(M) Tetracyclines TET

*strA* [*aph(3*′*)-Ib*], *strB* [*aph(6*′*)-Id*] Aminoglycosides STR *aadA1*, *aadA2*, *aadA5*, *aadA7*, *aadA24* Aminoglycosides STR *aph(3*′*)-Ia* Aminoglycosides KAN *aac(3*′*)-VI, aac(3*′*)-IId* Aminoglycosides GEN *bla*TEM-1 β-Lactams AMP *bla*OXA-1 β-Lactams AMP

**14**

**Table 6.**

*Typical E. coli resistance genes.*

given in **Table 7**.

*Typical E. coli bacteriocins, their receptor, translocation system, and mode of action [59, 60].*

#### **3.8 The probiotic** *E. coli*

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Probiotic bacteria act via a variety of means, including modulation of immune function, production of organic acids and antimicrobial compounds, interaction with resident microbiota, interfacing with the host, improving the gut barrier integrity, and enzyme formation [61]. Several *E. coli* strains were recognized as good and effective probiotics and are now used in drugs (see **Table 8**). The probiotic *E. coli* are applied to a variety of human conditions, including intestinal bowel diseases and diarrhea. Further it was shown that colonization of newborns led to reduced disease rates, lower incidence of allergies, and reduced mortality [62].

*E. coli* Nissle 1917 is nowadays often used as a reference strain or model microorganism in experimental biomedical studies, including recombinant manipulations of the strain in order to construct derivatives with novel properties [64]. One such example is the strain ŽP, which is a genetically modified Nissle 1917 possessing a bacterial conjugation-based "kill"-"anti-kill" antimicrobial system—a conjugative plasmid carrying the "kill" gene (colicin ColE7 activity gene) and a chromosomally encoded "anti-kill" gene (ColE7 immunity gene). Hence, in the process of conjugation, the conjugative plasmid transfers the "kill" gene into a recipient cell, where it is expressed and the recipient killed [65, 66].


#### **Table 8.**

*Probiotic E. coli drugs [62, 63].*

#### **3.9 The "workhorse"** *E. coli*

*E. coli* is known for its fast growing rate in chemically defined media and extensive molecular tools available for different purposes. All these make it an important model organism, which is also called the "workhorse" of molecular biology. Even though *E. coli* lacks many interesting features appreciated in biotechnology, such as growing at extreme temperatures or pH and the capacity to degrade toxic compounds, pollutants, or difficult to degrade polymers, it is much used in biotechnology also [67]. In **Table 9** contributions of *E. coli* to biology, medicine, and industry are listed.

The following recombinant pharmaceuticals were set up to be in vivo synthesized in *E. coli*: insulin, interleukin-2, human interferon-β, erythropoietin, human growth hormone, human blood clotting factors, pegloticase, taxol, and certolizumab. Further, *E. coli* is also used to produce biofuels and industrial chemicals such as phenol, ethanol, mannitol, and a variety of others [68].

**17**

**4. Conclusion**

**Table 9.**

To conclude, *E. coli* is a truly versatile microorganism possessing many facets—it is a well-known commensal bacterium, but some strains can be also pathogenic, even causing mortality, especially if the pathogenic strain acquired multiple resistance genes. However used as a probiotic it can improve health and in it can be

*Introductory Chapter: The Versatile Escherichia coli DOI: http://dx.doi.org/10.5772/intechopen.88882*

**Molecular biology, physiology, and genetics**

Identification of genes controlling antimicrobial

Elucidation of the structure and function of ATP

Relationship between genomic evolution and

**Genetic engineering and biotechnology**

*Contributions of E. coli to biology, medicine, and industry [68–70].*

drug tolerance in stationary phase

synthase

**Evolution**

adaptation

Role of global regulators and nucleotide metabolism in antibiotic tolerance

**Contribution Authors Year**

Transcription Stevens A 1960 Life cycle of lytic bacteriophages Ellis EL and Delbrück M 1939 Gene regulation of the *lac* operon Jacob F and Monod J 1961 Gene regulation of the *ara* operon Englesberg E, Irr J, Power J, and Lee N 1965 Discovery of restriction enzymes Linn S and Arber W 1968

Swarming motility behavior Harshey RM and Matsuyama T. 1994

Conjugal DNA transfer Tatum EL and Lederberg J 1947

Random nature of mutation Luria SE and Delbrück M 1943

Adaptive mutation Cairns J, Overbaugh J, and Miller S 1988 Role of historical contingency in evolution Blount ZD, Borland CZ, and Lenski RE 2008

Long-term fitness trajectories Wiser MJ, Ribeck N, and Lenski RE 2013 Effect of sexual recombination on adaptation Cooper TF 2007 Predator-prey interactions (bacteriophage) Chao L and Levin BR 1977

Generating precise deletions and insertions Link AJ, Phillips D, and Church GM 1997

Role of adaption, chance, and history in evolution Travisano M, Mongold JA, Bennet AF,

Origin of novel traits Blount ZD, Barrick JE, Davidson CJ,

Molecular cloning and recombinant DNA Cohen S, Chang A, Boyer H, and

Gene replacement Herring CD, Glasner JD, and Blattner

Watts-Tobin RJ

and Kornberg A

Brynildsen MP

Capaldi RA, Schulenberg B, Murray J, and Aggeler R

Barrick JE, Yu DS, Yoon SH, Oh TK, Schneider D, Lenski RE, and Kim JF

and Lenski RE

and Lenski RE

Helling R

FR

Hu Y and Coates AR 2005

Hansen S, Lewis K, and Vulić M 2008

1961

1958

2013

2000

2009

1995

2012

1973

2003

Elucidation of the genetic code Crick FH, Barnett L, Brenner S, and

DNA replication Lehman IR, Bessman MJ, Simms ES,

Metabolic control of persister formation Amato SM, Orman MA, and

*The Universe of Escherichia coli*

Produced by Ardeypharm GmbH,

Closest relatives CFT073, ABU83972

Contents 2.5–25 × 109

Recommended daily dose

Isolation date of the used strain(s)

Microcin production

Year of first publication describing the use in humans

**Table 8.**

**3.9 The "workhorse"** *E. coli*

*Probiotic E. coli drugs [62, 63].*

*E. coli* is known for its fast growing rate in chemically defined media and extensive molecular tools available for different purposes. All these make it an important model organism, which is also called the "workhorse" of molecular biology. Even though *E. coli* lacks many interesting features appreciated in biotechnology, such as growing at extreme temperatures or pH and the capacity to degrade toxic compounds, pollutants, or difficult to degrade polymers, it is much used in biotechnology also [67]. In **Table 9** contributions of *E. coli* to biology, medicine, and industry

**Drug name Mutaflor Symbioflor 2 Colinfant newborn**

Product Capsules Suspension Powder for preparation

CFU/capsule 1.5–4.5 × 107

Plasmid content 2 cryptic plasmids 12 plasmids No plasmids

*coli* strains (G1/2, G3/10, G4/9, G5, G6/7, and G8)

SymbioPharm GmbH, Herborn, Germany

2–4 ml (3.0–18 × 107

035,129, 0:169, rough, all H–

Microcin M, H47 Microcin S Data not available

absent)

K12, ATCC8739 (commensals)

1989 1998 1967

1915 1954 Data not available

CFU)

*E. coli* A0 34/86 strain

of per oral solution

Dyntec, Terezín, Czech Republic

dosis

three times/week

083:K24:H31

Data not available

CFT073, 536 (UPEC)

0.8–1.6 × 108

CFU/

CFU

CFU/ml 0.8–1.6 × 108

*E. coli* strain *E. coli* Nissle 1917 strain Six different *E.* 

Herdecke, Germany

1–2 capsules/day (2.5–50 × 109

Serotype 06:K5:H1 Variable including

Motility Motile (flagella present) Nonmotile (flagella

(UPEC)

CFU)

The following recombinant pharmaceuticals were set up to be in vivo synthesized in *E. coli*: insulin, interleukin-2, human interferon-β, erythropoietin,

human growth hormone, human blood clotting factors, pegloticase, taxol, and certolizumab. Further, *E. coli* is also used to produce biofuels and industrial chemicals such as phenol, ethanol, mannitol, and a variety of

**16**

are listed.

others [68].


#### **Table 9.**

*Contributions of E. coli to biology, medicine, and industry [68–70].*

### **4. Conclusion**

To conclude, *E. coli* is a truly versatile microorganism possessing many facets—it is a well-known commensal bacterium, but some strains can be also pathogenic, even causing mortality, especially if the pathogenic strain acquired multiple resistance genes. However used as a probiotic it can improve health and in it can be

employed as a good working "workhorse" in the laboratory as well as in biotechnological settings. The differentiation between commensal and pathogenic strains is not easy, as among the healthy gut microbiota pathogenic strains are hidden, and also commensal strains can become pathogenic due to horizontal gene transfer of mobile genetic elements possessing virulence genes [71]. Even though *E. coli* has been the object of research now for already more than 100 years, its versatility warrants new possibilities for investigation also in the future.
