Learning Objective
Describe the major mechanisms of bacterial drug resistance and explain how resistance traits are acquired and transferred among bacterial species.
Drug Resistance
Antibiotic resistance is a rapidly growing global threat, with some bacterial species now resistant to nearly all available antimicrobial agents. This shift has raised major concern about a coming post-antibiotic era, in which common infections may again become life-threatening.
Activity
Bacteria develop resistance through three major mechanisms:
Intrinsic Resistance
These are natural, built-in properties of a bacterial species that make it resistant to certain antibiotics.
Examples:
- The outer membrane of Gram-negative bacteria blocks large hydrophobic antibiotics
- Lack of cell wall → Mycoplasma resistant to β-lactams
Chromosome-Mediated Resistance
Caused by spontaneous chromosomal mutations affecting:
- Drug-target sites
- Permeability
- Efflux pumps
These mutations are passed to daughter cells during replication but not typically transferred between species.
Plasmid-Mediated Resistance
Plasmids (R plasmids) carry genes encoding:
- Drug-inactivating enzymes (β-lactamases, aminoglycoside-modifying enzymes)
- Efflux pumps
- Target-modifying enzymes
These plasmids can move between bacteria—even across genera—via conjugation, enabling rapid spread of resistance (e.g., from normal flora to pathogens).
This form of resistance is the most clinically important due to its efficiency in spreading.
