*2.2.3 Integrons and cassette system*

Both of them provide a simple mechanism for the acquisition of new genes. The DNA acquisition implies a single event of a site-specific recombination that causes the integration or removal of a single gene or a group of antibiotic resistance genes called cassette [30]. The integrons have certain components which allow a site-specific recombination system that recognizes and captures mobile genes. An integron includes a gene that codes for an integrase (Intl) and a site of specific recombination (*attI*) [31]. The sequences of the integrase enzymes allow integron classification in different classes (I–III) [32].

Genetic cassettes are small mobile elements that include a short sequence of 57 to 141 bp that are a specific recombination site. Cassettes can exist as free circular DNA molecules, and frequently they do not contain a promoter [30]. The lack of the promoter and the recombination sites make the recognition of the cassettes by Intl and Int13 and also by integrases encoded in the integrons possible. The integration of the cassettes to the integron structure allows the cassette genes' transcription from the characteristic integron promoter called Pant [30].

The dangerous feature of the transfer of antibiotic-resistant genes by transposons, integrons, or cassettes is the possibility that the bacterial receptor could acquire several classes of antibiotic resistance genes in a single event. A summary of the resistance to the different antibiotic classes, obtained by the intrinsic and acquired mechanisms, can be found in **Table 1**.


**175**

*Multidrug-Resistant Bacterial Foodborne Pathogens: Impact on Human Health and Economy*

Inhibits the synthesis of proteins by binding to the ribosomal 30S subunit

They inhibit DNA replication by binding to dihydrofolate reductase, an enzyme involved in the metabolism of folic

acid

They bind to the peptidyl transferase (PTC) center of the 50S ribosomal subunit to inhibit the translation elongation stage

They inhibit DNA synthesis by topoisomerases II

They inhibit the cell wall biosynthesis in Gram-positive bacteria. They block the binding of the substrate and the transglycosylases

They prevent protein elongation during translation by causing premature dissociation of the tRNA, inhibiting the 50S ribosomal subunit

They inhibit the synthesis of DNA by oxidation. The nitro group is reduced to toxic radical species

and IV

**Mode of action Mechanism of resistance**

*Intrinsic*

*Acquired*

*Intrinsic*

*Intrinsic*

*Intrinsic*

*Intrinsic*

*Intrinsic*

*Intrinsic*

*Acquired*

gen)

transporter)

transporter)

transporter) *Acquired*

transporter)

• Bacterial flow pumps (MexXY and ABC

• Enzymatic modification (*bla* KPC gene) • Ribosomal point mutation (*rrs* gene)

• Transposon Tn7 (*dhfrI* gene) [36]

• Target modification (*cfr* gen)

• Competitive inhibition of folic acid synthesis

• Bacterial flow pumps of amphenicols (Cml

• Target modification (*gyrA* and *parC* genes) • Bacterial flow pumps of amphenicols (AcrA

• Bacterial flow pumps of amphenicols (AcrF

• Ribosomal modification by methylation or mutation

• Bacterial flow pumps (ABC and MFS transporter) • Drug inactivation (*Lnu* and *Mph* genes) [39]

• Bacterial flow pumps (RND and BME transporter)

• Chromosomal mutations or plasmids acquired (*nim*

• Transposon Tn1546 (*van* gene) [38]

(*erm* and *msr* genes) [39]

• Reductive activation by altering • The metabolism of pyruvate (PFOR)

*DOI: http://dx.doi.org/10.5772/intechopen.88789*

**Antibiotic class/ antibiotics**

**Monobactams** [33, 35] *Aminoglycosides\** Streptomycin Kanamycin Neomycin Gentamicin Spectinomycin

**Diaminopyrimidines**

**Phenicols** [33] Chloramphenicol Thiamphenicol

**Fluoroquinolones**

**Glycopeptides** [33] Vancomycin Teicoplanin Streptogramins Virginamycin

**Lincosamides** [33] Lincomycin Clindamycin Pirlimycin

**Macrolides** [33] Erythromycin Oleandomycin Tylosin Spiramycin Tilmicosin

**Nitroimidazoles** [40] Metronidazole

[37] Enrofloxacin Danofloxacin Marbofloxacin

[33] Trimethoprim **Antibiotic class/ antibiotics Mode of action Mechanism of resistance Monobactams** [33, 35] *Aminoglycosides\** Streptomycin Kanamycin Neomycin Gentamicin Spectinomycin Inhibits the synthesis of proteins by binding to the ribosomal 30S subunit *Intrinsic* • Bacterial flow pumps (MexXY and ABC transporter) • Enzymatic modification (*bla* KPC gene) • Ribosomal point mutation (*rrs* gene) **Diaminopyrimidines** [33] Trimethoprim They inhibit DNA replication by binding to dihydrofolate reductase, an enzyme involved in the metabolism of folic acid *Acquired* • Transposon Tn7 (*dhfrI* gene) [36] *Intrinsic* • Competitive inhibition of folic acid synthesis **Phenicols** [33] Chloramphenicol Thiamphenicol They bind to the peptidyl transferase (PTC) center of the 50S ribosomal subunit to inhibit the translation elongation stage *Intrinsic* • Target modification (*cfr* gen) • Bacterial flow pumps of amphenicols (Cml transporter) **Fluoroquinolones** [37] Enrofloxacin Danofloxacin Marbofloxacin They inhibit DNA synthesis by topoisomerases II and IV *Intrinsic* • Target modification (*gyrA* and *parC* genes) • Bacterial flow pumps of amphenicols (AcrA transporter) **Glycopeptides** [33] Vancomycin Teicoplanin Streptogramins Virginamycin They inhibit the cell wall biosynthesis in Gram-positive bacteria. They block the binding of the substrate and the transglycosylases *Intrinsic* • Bacterial flow pumps of amphenicols (AcrF transporter) *Acquired* • Transposon Tn1546 (*van* gene) [38] **Lincosamides** [33] Lincomycin Clindamycin Pirlimycin They prevent protein elongation during translation by causing premature dissociation of the tRNA, inhibiting the 50S ribosomal subunit *Intrinsic* • Ribosomal modification by methylation or mutation (*erm* and *msr* genes) [39] • Bacterial flow pumps (ABC and MFS transporter) • Drug inactivation (*Lnu* and *Mph* genes) [39] **Macrolides** [33] Erythromycin Oleandomycin Tylosin Spiramycin Tilmicosin **Nitroimidazoles** [40] Metronidazole They inhibit the synthesis of DNA by oxidation. The nitro group is reduced to toxic radical species *Intrinsic* • Bacterial flow pumps (RND and BME transporter) • Reductive activation by altering • The metabolism of pyruvate (PFOR) *Acquired*

• Chromosomal mutations or plasmids acquired (*nim*

gen)

*Multidrug-Resistant Bacterial Foodborne Pathogens: Impact on Human Health and Economy DOI: http://dx.doi.org/10.5772/intechopen.88789*

*Pathogenic Bacteria*

*2.2.2 Transposons*

*2.2.3 Integrons and cassette system*

different classes (I–III) [32].

**Antibiotic class/ antibiotics**

**Beta-lactam** [33] *Penicillins\** Penicillin G and V Cloxacillin Ampicillin Carbenicillin *Cephalosporins\** Cephaloridine Cephalexin Cefuroxime Moxalactam Ceftiofur Cefoperazone Cefepime *Inhibitors Beta-lactamase\** Clavulanate Sulbactam Tazobactam *Carbapenems\** Imipenem/cilastatin Aztreonam

These are already known as jumping genes. These are short chains of DNA that jump from chromosome to plasmid or vice versa. DNA transfer can occur between bacterial chromosome, plasmids, and bacteriophages. The most salient feature of transposons is that DNA acquired is easily integrated into the host chromosome or plasmids. Unlike plasmids, jumping genes are not self-replicating, and they must be

Both of them provide a simple mechanism for the acquisition of new genes. The DNA acquisition implies a single event of a site-specific recombination that causes the integration or removal of a single gene or a group of antibiotic resistance genes called cassette [30]. The integrons have certain components which allow a site-specific recombination system that recognizes and captures mobile genes. An integron includes a gene that codes for an integrase (Intl) and a site of specific recombination (*attI*) [31]. The sequences of the integrase enzymes allow integron classification in

Genetic cassettes are small mobile elements that include a short sequence of 57 to 141 bp that are a specific recombination site. Cassettes can exist as free circular DNA molecules, and frequently they do not contain a promoter [30]. The lack of the promoter and the recombination sites make the recognition of the cassettes by Intl and Int13 and also by integrases encoded in the integrons possible. The integration of the cassettes to the integron structure allows the cassette genes' transcription

The dangerous feature of the transfer of antibiotic-resistant genes by transposons, integrons, or cassettes is the possibility that the bacterial receptor could acquire several classes of antibiotic resistance genes in a single event. A summary of the resistance to the different antibiotic classes, obtained by the intrinsic and

**Mode of action Mechanism of resistance**

*Acquired* • Plasmids • Transposons • Integrons

*Intrinsic*

transporter)

(*bla*TEM-1, *bla*NDM-1, *bla*KPC, *bla SHV*, *blaCTX-M*, *AmpC*, *bla*VIM, *bla*OXA, and *blaIMI* genes) [34]

• Bacterial flow pumps (RND, ABC, and 233

kept within a self-replicating structure to replicate them [19].

from the characteristic integron promoter called Pant [30].

Act as suicide substrates for penicillin-binding proteins (PBP) (transpeptidases) They inhibit cell wall biosynthesis, specifically the peptidoglycan structure

acquired mechanisms, can be found in **Table 1**.

**174**


#### **Table 1.**

*Modes of action to different classes of antibiotics and their mechanisms of resistance.*
