Bacterial Antibiotic Resistance

β-Lactamase Resistance

• Exposure to low doses of antibiotics selects for bacteria to produce β-lactamase resistance.
• There are four classes of β-lactamase produced by organisms: class A, class B, class C, and class D.

Regulation of β-Lactamase

• Class A, C, and D β-lactamase are regulated by chromosomal genes and are induced by penicillin and cephalosporin.
• Class B β-lactamase is located on a conjugated plasmid and does not require induction by penicillin or cephalosporin.

Characteristics of β-Lactamases

• β-Lactamases of Staphylococcus aureus have a low molecular weight and a wide spectrum of activity.
• They have high efficiency in destroying penicillin group and most first- and second-generation cephalosporins.

Methicillin Resistance

• Methicillin resistance is not related to β-lactamase production since methicillin does not have a β-lactam ring structure.
• About 85% of MRSA (Methicillin-resistant Staphylococcus aureus) overproduce penicillin binding protein PBP 2a and PBP 2’.

Mechanism of Resistance

• Production of β-lactamase is the principal mechanism of resistance to β-lactam antibiotics in bacteria.
• β-Lactamase leads to hydrolysis of penicillin, rendering it ineffective.

Types of β-Lactamase

• Two types of β-lactamase: inducible (e.g., E. coli) and constitutive (e.g., Staphylococci, Streptococci, Neisseria, and Clostridium species).
• Constitutive β-lactamase is very effective against penicillin, but its activity against methicillin, cephalosporin, imipenem, and oferaroxamin is variable.