*4.1.2. Biochemistry of antibiotic resistance*

As so many scientists have been struggling to study the biochemical mechanisms of antibi‐ otic resistance, nowadays there is a large pool of related valuable information left. Biochemi‐ cal mechanisms may be varied among different bacterial species, but can be mainly classified into four categories (Fig. 2). In fact, each of these four categories also contains an amazing diversity of resistance mechanisms. Sometimes a single bacterial strain may pos‐ sess several types of resistance mechanisms. Each of the four main categories will be dis‐ cussed respectively below.

#### *4.1.2.1. Antibiotic inactivation*

Biochemical strategies include enzymatic modification and redox mechanisms (which is less important and will not be elaborated in this paper). Enzymes can be divided into two gener‐ al classes: those such as β-lactamases that degrade antibiotics and others that perform chem‐ ical transformations. The antibiotic β-lactam has a four-atom ring known as a beta-lactamin. The β-lactamase enzyme breaks that ring open, destroying the antibacterial properties of the drugs. β-lactamase consists of enzymes with a serine residue at the active site, and metal‐ loenzymes with zinc ion as a cofactor and with a separate heritage [37]. β-lactamase en‐ zymes are the most common and important weapons for Gram-negative bacteria to resist the antibiotics β-lactam [38]. The group transfer approaches are the most diverse and in‐ clude the modification by acyltransfer, phosphorylation, glycosylation, nucleotidylation, ri‐ bosylation, and thiol transfer. They can inactivate antibiotics (aminoglycosides, chloramphenicol, streptogramin, macrolides or rifampicin) by chemical substitution. These modifications reduce the affinity of antibiotics to a target [85]. For example, enzymatic mod‐ ification is the most prevalent mechanism to destroy aminoglycosides in clinic. Aminoglyco‐ side modifying enzymes can be divided into three classes: acetyltransferases, nucleotidyltranferases, and phosphotransferases; they mainly catalyze the modification at – OH or –NH2 groups of the 2-deoxystreptamine nucleus or the sugar moieties [39]. There are a large number of genes in the chromosomes and other mobile genetic elements coding for these enzymes which let the bacteria resist to more new antibiotics as well as horizontally spread their resistance among bacteria more easily. As a consequence, almost all pathogens are resistant to aminoglycosides through modifying enzymes [39].
