**1. Introduction**

Bacterial survival and persistence in an inappropriate substrate can be defined as the ability of bacteria to tolerate exposure to lethal concentrations of bactericidal antibiotics. This view

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was first noticed in 1944 regarding that treatment of cultures of *Staphylococcus aureus* with high concentrations of penicillin did not kill all the strains, and that a fraction of the order of 10−6 of these strains survived. Bacteria can cause frequently infections in humans, and the resistance to antibiotics is a primary cause of disease and sometimes death in the intensivecare units of hospitals worldwide [1] and the cause of numerous clinical problems [2]. The development and increase of resistance among pathogens causing nosocomial and community-acquired infections are known to be associated with the widespread utilization of antibiotics [3–5].

The presence of antibiotic resistance strains in environment may be understood as a response to the selective pressures. Thus, any antibiotic use will provide a selective pressure that perpetuates resistant bacteria. The introduction of antibiotics in the treatment of diseases that were prior incurable, enabled the effective treatment of these, promoting the increase in longevity. This kind of medicine is widely used in the treatment of people in the community and health services and is also used to treat animals in agricultural environments. Thus, the increasing levels of resistance are compromising the effectiveness of them. Therefore, it is essential that we assess the use of antibiotics carefully, regardless of setting, and use them only when necessary, to avoid promoting the development of resistance among bacteria [12]. Various infections are caused by important pathogens, such as *Staphylococcus aureus*, and up to 50% are resistant to stronger drugs, such as methicillin [13], and with *E. coli* [12, 14–16] the

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The food supply can be a source of antimicrobial-resistant and virulent *E. coli* strains that could be lethal to humans or, in a major scale, can cause intestinal as well as extra intestinal infections. *Escherichia coli* (**Figure 1**) is a ubiquitous and versatile microorganism, moving from commensal to opportunistic and specialized virulent bacteria, with potential to cause different diseases. To cause infection, harmless commensal *E. coli* can acquire a set of combination of mobile genetic elements to become a highly adapted pathogen capable of causing different diseases in different hosts, ranging from gastroenteritis to extra intestinal infections of the urinary tract, bloodstream, and central nervous system. Seven diarrheagenic and two

Interestingly, one outbreak happens, caused by one not expected *E. coli* pathotype [18] in 2011. An uncommon high number of haemolytic uremic syndrome (HUS) cases were reported in

extra intestinal *E. coli* pathovars can cause disease in various hosts.

**Figure 1.** *E. coli* in scanning electronic microscopy [17].

resistant trait is growing.

Antimicrobial is a general term for drugs, chemicals, and/or other substances that either kill or slow the microbial metabolism. Various antimicrobial agents that are in use today are antibiotic, antiviral, antifungal, and antiparisitic drugs. An antibiotic is a type of antimicrobial agent produced by a fungi or a bacterium that has a direct influence on other microbes, specifically bacteria. Many of antibiotic resistance genes are found on transposons, integrons, and/or plasmids that can be transferred to another bacteria belonging to the same or different species [6] and resistance elements can be transferred to the human commensal or pathogenic microbiome [7].

The genes conferring resistance to antibiotics have been widely distributed in the environment since before the introduction of antibiotic chemotherapies, but human activities are probably the major driven force of the resistant bacteria found in air and water, principally with *S. aureus* and *E. coli* isolates. The antibiotic presence in the environment can exert selective pressure on the organisms living closely, but the mechanisms of cross resistance to antibiotics are unknown [6].

Studies with animals [8] showed that the proximity with humans has the tendency to generate more antibiotic-resistant enteric bacteria as saw with African baboons. With birds, a study [9] showed that 8% of *E. coli* isolated from arctic region presented resistance. This can enhance the pressure of antibiotic resistance by an anthropogenic activity. In pristine environments, the determinants of an antibiotic resistance existed naturally and were probably subjected to horizontal gene transfer [10]. This predisposition for the genetic exchange of resistance elements has facilitated the antibiotic resistance in pathogenic bacteria.

Antibiotics kill or inhibit bacteria that are susceptible to that antibiotic. Bacteria that are intrinsically resistant or that can acquire resistance will survive and replace the drug-susceptible bacteria. The production of an antibiotic is associated with the presence of genes encoding one or more self-protection processes. Antibiotic biosynthesis gene clusters that encode resistance proteins specific to the compound made (modification of the compound or target) or multifunctional (efflux systems) are important systems. The resistance genes that are contiguous with the biosynthesis genes could be involved in regulation of the biosynthetic pathway.

There are consistent results [11] that showed that antibiotic resistance genes are found in natural sources. Another form of resistance in isolates not producing antibiotics is the mutation of the target gene product, which reduces or prevents inhibition by antibiotic binding. Spontaneous mutations causing resistance often lead to different bacterial phenotypes.

The presence of antibiotic resistance strains in environment may be understood as a response to the selective pressures. Thus, any antibiotic use will provide a selective pressure that perpetuates resistant bacteria. The introduction of antibiotics in the treatment of diseases that were prior incurable, enabled the effective treatment of these, promoting the increase in longevity. This kind of medicine is widely used in the treatment of people in the community and health services and is also used to treat animals in agricultural environments. Thus, the increasing levels of resistance are compromising the effectiveness of them. Therefore, it is essential that we assess the use of antibiotics carefully, regardless of setting, and use them only when necessary, to avoid promoting the development of resistance among bacteria [12].

Various infections are caused by important pathogens, such as *Staphylococcus aureus*, and up to 50% are resistant to stronger drugs, such as methicillin [13], and with *E. coli* [12, 14–16] the resistant trait is growing.

The food supply can be a source of antimicrobial-resistant and virulent *E. coli* strains that could be lethal to humans or, in a major scale, can cause intestinal as well as extra intestinal infections. *Escherichia coli* (**Figure 1**) is a ubiquitous and versatile microorganism, moving from commensal to opportunistic and specialized virulent bacteria, with potential to cause different diseases. To cause infection, harmless commensal *E. coli* can acquire a set of combination of mobile genetic elements to become a highly adapted pathogen capable of causing different diseases in different hosts, ranging from gastroenteritis to extra intestinal infections of the urinary tract, bloodstream, and central nervous system. Seven diarrheagenic and two extra intestinal *E. coli* pathovars can cause disease in various hosts.

Interestingly, one outbreak happens, caused by one not expected *E. coli* pathotype [18] in 2011. An uncommon high number of haemolytic uremic syndrome (HUS) cases were reported in

**Figure 1.** *E. coli* in scanning electronic microscopy [17].

was first noticed in 1944 regarding that treatment of cultures of *Staphylococcus aureus* with high concentrations of penicillin did not kill all the strains, and that a fraction of the order of 10−6 of these strains survived. Bacteria can cause frequently infections in humans, and the resistance to antibiotics is a primary cause of disease and sometimes death in the intensivecare units of hospitals worldwide [1] and the cause of numerous clinical problems [2]. The development and increase of resistance among pathogens causing nosocomial and community-acquired infections are known to be associated with the widespread utilization of anti-

100 *Escherichia coli* Escherichia coli - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications

Antimicrobial is a general term for drugs, chemicals, and/or other substances that either kill or slow the microbial metabolism. Various antimicrobial agents that are in use today are antibiotic, antiviral, antifungal, and antiparisitic drugs. An antibiotic is a type of antimicrobial agent produced by a fungi or a bacterium that has a direct influence on other microbes, specifically bacteria. Many of antibiotic resistance genes are found on transposons, integrons, and/or plasmids that can be transferred to another bacteria belonging to the same or different species [6] and resistance elements can be transferred to the human commensal or pathogenic

The genes conferring resistance to antibiotics have been widely distributed in the environment since before the introduction of antibiotic chemotherapies, but human activities are probably the major driven force of the resistant bacteria found in air and water, principally with *S. aureus* and *E. coli* isolates. The antibiotic presence in the environment can exert selective pressure on the organisms living closely, but the mechanisms of cross resistance to anti-

Studies with animals [8] showed that the proximity with humans has the tendency to generate more antibiotic-resistant enteric bacteria as saw with African baboons. With birds, a study [9] showed that 8% of *E. coli* isolated from arctic region presented resistance. This can enhance the pressure of antibiotic resistance by an anthropogenic activity. In pristine environments, the determinants of an antibiotic resistance existed naturally and were probably subjected to horizontal gene transfer [10]. This predisposition for the genetic exchange of resistance ele-

Antibiotics kill or inhibit bacteria that are susceptible to that antibiotic. Bacteria that are intrinsically resistant or that can acquire resistance will survive and replace the drug-susceptible bacteria. The production of an antibiotic is associated with the presence of genes encoding one or more self-protection processes. Antibiotic biosynthesis gene clusters that encode resistance proteins specific to the compound made (modification of the compound or target) or multifunctional (efflux systems) are important systems. The resistance genes that are contiguous with the biosynthesis genes could be involved in regulation of

There are consistent results [11] that showed that antibiotic resistance genes are found in natural sources. Another form of resistance in isolates not producing antibiotics is the mutation of the target gene product, which reduces or prevents inhibition by antibiotic binding. Spontaneous mutations causing resistance often lead to different bacterial phenotypes.

ments has facilitated the antibiotic resistance in pathogenic bacteria.

biotics [3–5].

microbiome [7].

biotics are unknown [6].

the biosynthetic pathway.

Europe, most precisely in Germany. The implicated agent was an enterohemorrhagic *E. coli* (EHEC), which presented virulence traits of both, a verotoxigenic *E. coli* (VTEC) and enteroaggregative *E. coli* (EAEC).

A relevant study involving enterotoxigenic *E. coli* STb toxin was conducted in 2014 [19], regarding the STb toxigenicity. STb is a heat-resistant toxin responsible for diarrhea in farm animals and in humans as well. The toxic effect of STb in host cells is due to allowing the passage of electrolytes and water through the paracellular space. The authors [19] demonstrated that STb could promote the delocalization of transmembrane proteins such as claudin-1.

This event among others can prove how the versatility of this bacterium can reach a worldwide proportion, with a high concern for public health. These types of outbreaks are not solely a consequence of health conditions in developing countries. With the increase in international travel and trade globalization, diarrheagenic *E. coli* has become a worldwide public health threat [20].

On the other hand, the main characteristic of intracellular bacteria is the ability to survive within the macrophages. In this context, some important pathogens are *L. monocytogenes, Mycobacterium tuberculosis* and, *M. leprae*. Invasion of the macrophage is also a parasite's getaway strategy. Though paradoxical, the last mechanism is benign to the harborer, while the lack of cell penetration by bacteria can induce a strong inflammatory effect and excessive injury to the host.

1. Antibodies

2. Cytokines produced by T cells

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**I. Natural barriers against infection II. Innate immunity III. Acquired immunity**

Antibiotic Resistance among *Escherichia coli*: Isolates and Novel Approaches to the Control of *E. coli* Infections

protein, complement)

macrophages

1. Integrity of skin and mucosa 1. Extracellular molecules (C reactive

2. Mucociliar movement 2. Natural killer cells, neutrophils,

3. pH variations 3. Chemokines, cytokines – 4. Antimicrobial substances – –

Adaptive immunity, principally by means of antibodies plays an important function versus bacteria outside of the cell. Antibodies may exert its inhibition in three steps: (i) opsonization, (ii) activation of the complementary system, and (iii) furthering the neutralization of bacteria

Extracellular bacteria are prone to undoing when phagocytozed. So subverting this system, they developed substances such as evasive mechanism with an antiphagocytic system.

Antibodies directed against these substances not only avoid their action, also facilitate phagocytosis, while neutrophils and macrophages have receivers for the fc part of immunoglobulin

The antibodies also coassist in the destruction of complement by bacteria, and activate this system by the classical pathway. Through neutralization mechanism, IgA antibodies, in particular, can bind to bacteria and therefore prevent the latter from settling on the intestinal mucosa and the respiratory tract. Antibodies bind frequently to toxins produced from bacteria, such as tetanus (*Clostridium tetani*) and diphtheria toxin (*Corynebacterium diphtheriae*), and neutralize the action of these metabolites. The fine balance between health and disease is found in this scenario, in which deficiency is as much as excess may result in tissue damage.

A mature human gut harbors a vast number of bacterial resident microbiota, accounting for more than 1014 individual bacteria. Notably, the composition of the microbiota is individual host specific and the type of species living in the gastrointestinal tract varies with the host age, diet, habits, health, and idiosyncratic status [22]. The intestinal mucosa is a first contact between the immune system and the external environment and plays a central role in a

or their metabolites.

Note: Ref. [21] with modifications.

**Table 1.** Barriers against infectious microorganisms.

(opsonization).

**3.** *E. coli* **antibiotic resistance**

On the other hand, antibiotic resistance rates in *E. coli* are rapidly rising, especially concerning to the use of fluoroquinolones and third- and fourth-generation cephalosporin. These strains are acquired predominantly in the community [12]. In these conditions, drug-resistant *E. coli* are readily acquired via the consumption of contaminated food and beverage. Some authors [14] studied 287 *E. coli* samples isolated from meats regarding their virulence factors. They observed that drugresistant isolates had similar characteristics to those collected from the same types of meat.

This review shows the immune view of *E. coli*, and focus on the presence of these bacteria highlighting the acquisition of resistance and discussing various aspects of *E. coli* pathotypes. Because the antibiotic treatment is our primary method of threaten diseases, studies on this field are important to a better understanding of bacterial evasion, circumventing, and subverting mechanisms to acquire resistance characteristics.
