**2. Intrinsic resistance of** *Pseudomonas aeruginosa*

*P. aeruginosa* shows inherent resistance to antimicrobial agents through a variety of mecha‐ nisms: (1) decreased permeability of the outer membrane, (2) efflux systems which actively pump antibiotics out of the cell, and (3) production of antibiotic-inactivating enzymes [6].

#### **2.1. Outer membrane permeability**

The outer membrane of Gram-negative bacteria is a barrier which prevents large hydrophilic molecules to pass through it. Aminoglycosides and colistin interact with lipopolysaccharides changing the permeability of the membrane in order to pass whereas beta-lactams and quinolones need to diffuse through certain porin channels.

Bacteria produce two major classes of porins: general; which allow almost any hydrophilic molecule to pass [7] and specific; which have binding sites for certain molecules, allowing them to be oriented and pass in the most energy-efficient way [8].

Most bacteria posses lots of general porins and relatively few specific ones. However, the exact opposite occurs for *P. aeruginosa* that expresses mainly specific porins [7].

#### **2.2. Efflux systems**

*P. aeruginosa* expresses several efflux pumps that expel drugs together with other substances out of the bacterial cell. These pumps consist of three proteins: (1) a protein transporter of the cytoplasmatic membrane that uses energy in the form of proton motive force, (2) a periplasmic connective protein, and (3) an outer membrane porin [5].

Most antibiotics- except polymyxins- are pumped out [9,10] by these efflux systems (Table 1) therefore their first two components are named multidrug efflux (Mex) along with a letter (e.g. MexA and MexB). The outer membrane porin is called Opr along with a letter (e.g. OprM) [11].

### **2.3. Antibiotic-inactivating enzymes**

*P. aeruginosa* belongs to the SPICE group of bacteria (*Serratia* spp., *P. aeruginosa,* Indole positive *Proteus, Citrobacter* spp., *Enterobacter* spp.). These microorganisms share a common character‐ istic: the ability to produce chromosomal-encoded and inducible AmpC beta-lactamases. These are cephalosporinases that hydrolyze most beta-lactams and are not inhibited by the beta lactamase inhibitors.

Another endogenous beta-lactamase produced by *P. aeruginosa* is the class D oxacillinase PoxB [12,13]. This enzyme however has only been found in laboratory mutants and is not clinically significant.

*Pseudomonas aeruginosa*: Multi-Drug-Resistance Development and Treatment Options http://dx.doi.org/10.5772/55616 35


**Table 1.** Efflux systems of *P. aeruginosa*.

tion of additional mechanisms or is a consequence of mutational events under selective

*P. aeruginosa* shows inherent resistance to antimicrobial agents through a variety of mecha‐ nisms: (1) decreased permeability of the outer membrane, (2) efflux systems which actively pump antibiotics out of the cell, and (3) production of antibiotic-inactivating enzymes [6].

The outer membrane of Gram-negative bacteria is a barrier which prevents large hydrophilic molecules to pass through it. Aminoglycosides and colistin interact with lipopolysaccharides changing the permeability of the membrane in order to pass whereas beta-lactams and

Bacteria produce two major classes of porins: general; which allow almost any hydrophilic molecule to pass [7] and specific; which have binding sites for certain molecules, allowing them

Most bacteria posses lots of general porins and relatively few specific ones. However, the exact

*P. aeruginosa* expresses several efflux pumps that expel drugs together with other substances out of the bacterial cell. These pumps consist of three proteins: (1) a protein transporter of the cytoplasmatic membrane that uses energy in the form of proton motive force, (2) a periplasmic

Most antibiotics- except polymyxins- are pumped out [9,10] by these efflux systems (Table 1) therefore their first two components are named multidrug efflux (Mex) along with a letter (e.g. MexA and MexB). The outer membrane porin is called Opr along with a letter (e.g. OprM) [11].

*P. aeruginosa* belongs to the SPICE group of bacteria (*Serratia* spp., *P. aeruginosa,* Indole positive *Proteus, Citrobacter* spp., *Enterobacter* spp.). These microorganisms share a common character‐ istic: the ability to produce chromosomal-encoded and inducible AmpC beta-lactamases. These are cephalosporinases that hydrolyze most beta-lactams and are not inhibited by the

Another endogenous beta-lactamase produced by *P. aeruginosa* is the class D oxacillinase PoxB [12,13]. This enzyme however has only been found in laboratory mutants and is not clinically

**2. Intrinsic resistance of** *Pseudomonas aeruginosa*

quinolones need to diffuse through certain porin channels.

to be oriented and pass in the most energy-efficient way [8].

connective protein, and (3) an outer membrane porin [5].

**2.3. Antibiotic-inactivating enzymes**

beta lactamase inhibitors.

significant.

opposite occurs for *P. aeruginosa* that expresses mainly specific porins [7].

**2.1. Outer membrane permeability**

**2.2. Efflux systems**

pressure.

34 Infection Control
