**2. Antimicrobial resistance against last resort antibiotics in** *E. coli*

Generally, there are five main mechanisms by which gram-negative organisms develop resistance: First, bacteria can carry genes coding for enzymes, such as beta-lactamases, hydrolyzing, and inactivating beta-lactam antibiotics. Second, mutations can occur in the genes for binding sites for antibiotics changing the specific target or its function. Third, alterations of the membrane porins result in reduced permeability. Fourth, bacteria can express efflux pumps to actively transport antibiotics out of the cell, and finally, fifth, alternate metabolic pathways can bypass paths inhibited by antibiotics [13, 14].

Resistance in gram-negative bacteria can be intrinsic, arise, or be acquired and is often composed of a combination of resistance mechanisms like beta-lactamases, porin deletions, and efflux pumps [15]**.**

Acquired bacterial resistance may be due to mutations in chromosomal genes and by horizontal gene transfer. The intrinsic resistance appears due to inherent structural or functional characteristics (**Figure 2**).

The intrinsic resistance of some gram-negative bacteria to many compounds is due to an inability of these agents to cross the outer membrane: For example, the glycopeptide antibiotic vancomycin inhibits peptidoglycan cross-linking by binding

**Figure 1.** *Transfer of resistance between bacteria through plasmid exchange.*

*DOI: http://dx.doi.org/10.5772/intechopen.104955* Escherichia coli *(*E. coli*) Resistance against Last Resort Antibiotics and Novel Approaches…*

to target d-Ala-d-Ala peptides but is only normally effective in gram-positive bacteria as, in gram-negative organisms, it cannot cross the outer membrane and access these peptides in the periplasm [17]**.**
