Antimicrobial Resistance: Mechanisms and Genetic Transfer Explained

The central dogma of molecular biology describes how genetic information flows from DNA to RNA to protein through three key processes: DNA replication creates two identical DNA copies from one original strand by separating the double helix and adding complementary nucleotides (adenine-thymine, guanine-cytosine); transcription transfers DNA information to messenger RNA (mRNA) using RNA polymerase, where uracil replaces thymine; and translation occurs in ribosomes where mRNA codons (three nitrogenous bases) are read by transfer RNA molecules carrying specific amino acids, which join together to form proteins.

The central dogma describes the flow of genetic information in living organisms: DNA replication (duplication), transcription (DNA to mRNA), and translation (mRNA to protein). DNA replication involves three main steps: helicase separates DNA strands by breaking hydrogen bonds between complementary base pairs (A-T with 2 bonds, C-G with 3 bonds), creating a Y-shaped replication fork; DNA polymerase adds complementary nucleotides to each original strand; DNA ligase seals gaps between newly synthesized fragments. Replication is semi-conservative, with each new DNA molecule containing one original and one new strand, occurring with high accuracy (one error per billion base pairs). Transcription synthesizes mRNA using one DNA strand as template, with RNA polymerase binding to promoter sequences near genes. The DNA double helix unwinds, exposing the template strand. RNA polymerase adds complementary RNA nucleotides: adenine in DNA pairs with uracil in RNA, cytosine with guanine, guanine with cytosine, and thymine with adenine. After reaching termination signals, the enzyme releases mRNA, and DNA strands rejoin. Translation occurs in ribosomes within the cytoplasm, reading mRNA codons to assemble amino acids into polypeptide chains. The process involves three stages: initiation (ribosome binds mRNA at start codon AUG with methionine-carrying tRNA), elongation (tRNAs deliver amino acids as anticodons match codons, forming peptide bonds), and termination (stop codons UAA, UAG, or UGA trigger release factors to detach the polypeptide). In prokaryotes, transcription and translation can occur simultaneously due to the absence of a nuclear membrane.

The central dogma of molecular biology describes the flow of genetic information from DNA to protein through three key processes: DNA replication (where double-stranded DNA unwinds and each strand serves as a template for a new complementary strand, following complementarity and semi-conservative principles), transcription (where RNA polymerase synthesizes mRNA from a DNA template strand, with A pairing with U and T pairing with A), and translation (where ribosomes read mRNA codons to assemble amino acids into polypeptide chains, with A pairing with U and G pairing with C). These processes occur in the nucleus (replication and transcription) and cytoplasm (translation), involving enzymes such as DNA polymerase, RNA polymerase, and ligase.

DNA replication is a semi-conservative process where DNA polymerase synthesizes new strands using the original DNA as a template, with the leading strand synthesized continuously and the lagging strand in Okazaki fragments; transcription converts DNA to mRNA using RNA polymerase, producing messenger RNA, transfer RNA, and ribosomal RNA; translation occurs at ribosomes where mRNA codons are read by tRNA anticodons to assemble amino acids into proteins, with start codons (AUG) initiating and stop codons (UAA, UAG, UGA) terminating the process, and the genetic code is degenerate with multiple codons encoding the same amino acid.

The central dogma of molecular biology describes the flow of genetic information: DNA stores genetic information, which is transcribed to RNA, and then translated to proteins. DNA replication is semi-conservative (each daughter DNA molecule contains one original strand and one newly synthesized strand), semi-discontinuous (one strand is synthesized continuously as the leading strand while the other is synthesized discontinuously as the lagging strand with Okazaki fragments), and anti-parallel (the two strands run in opposite directions). Transcription copies only one DNA strand (template strand) to produce RNA, while replication copies both strands. Translation occurs in ribosomes where mRNA codons are read to assemble amino acids into proteins, with the start codon always being AUG (coding for methionine) and stop codons (UAA, UAG, UGA) terminating the process.

Bacteria contain two types of genetic material: the bacterial chromosome and bacterial plasmids. The bacterial chromosome is larger and more complex, containing most of the bacterial DNA. Plasmids are smaller, circular pieces of DNA that have separated from the chromosome and float freely inside the bacterial cell. Plasmids are readily accessible and can be transferred between bacteria, while chromosomes remain within the main cellular structure.

Bacterial chromosomes are circular (วงแหวน) unlike the linear chromosomes found in humans and other animals. A plasmid (พลาสมิด) is a small, circular DNA molecule found in bacteria that exists separately from the bacterial chromosome. Plasmids can carry genes that provide bacteria with specific traits, such as antibiotic resistance. In genetic engineering, plasmids serve as vectors to carry foreign DNA into bacterial cells.

Bacterial genetic material is divided into two types: (1) Chromosome - carries essential genetic information necessary for basic cellular functions, (2) Plasmid - carries secondary genetic information that provides additional traits (such as antibiotic resistance). The chromosome is essential for bacterial survival, while plasmids provide supplementary traits that may be advantageous in certain environments.

Bacterial chromosomes are typically circular, double-stranded DNA molecules with a single origin of replication, lacking histone proteins, centromeric sequences, and heterochromatin regions, and are located in the nucleoid region of the cytoplasm. Bacterial plasmids are extra-chromosomal, self-replicating DNA molecules that are most commonly circular and negatively supercoiled, ranging in size from less than 5 kilobase pairs to several hundred kilobase pairs, and can be classified as low copy number (1-3 copies per cell) or high copy number (10-100 copies per cell) plasmids.

Bacterial chromosomes are single, circular, double-stranded DNA molecules that are supercoiled to fit within the cell. Plasmids are smaller, circular, double-stranded DNA molecules that exist independently of the chromosome. Plasmids contain fewer genes (typically 10 genes compared to 4000 genes on the chromosome) and can be transferred between bacteria. This independent replication and transfer capability makes plasmids important for bacterial adaptation and antibiotic resistance spread.

Antibiotics targeting cell wall synthesis include penicillins (beta-lactams inhibiting transpeptidases), cephalosporins (generation-based spectrum evolution), and glycopeptides like vancomycin (binding D-Ala-D-Ala tails). Cell wall-disrupting antibiotics are most effective against gram-positive bacteria. Ribosome-targeting antibiotics include aminoglycosides (corrupting 30S subunit, bactericidal, oxygen-dependent), tetracyclines (blocking tRNA docking, bacteriostatic), and macrolides (blocking 50S exit tunnel, bacteriostatic). Each targets specific bacterial processes, and understanding these mechanisms helps predict spectrum and side effects.

Antibiotics work through four major mechanisms: (1) Cell wall synthesis inhibition by beta-lactams (penicillin, cephalosporins) binding to penicillin-binding proteins and inhibiting transpeptidase enzymes, preventing cross-link formation in peptidoglycan; (2) Protein synthesis inhibition by aminoglycosides (gentamicin) binding to 30S subunit preventing aminoacyl-tRNA attachment, tetracyclines (doxycycline) blocking amino acid addition, and macrolides (erythromycin) binding to 50S subunit blocking translocation; (3) Nucleic acid synthesis inhibition by fluoroquinolones (ciprofloxacin) inhibiting DNA gyrase essential for DNA replication, and rifamycins (rifampin) inhibiting RNA polymerase preventing mRNA synthesis; (4) Metabolic pathway inhibition by sulfonamides and trimethoprim blocking folate synthesis enzymes. Each mechanism targets essential bacterial processes, enabling selective toxicity against bacteria while sparing human cells.

Many antibiotics work by inhibiting bacterial cell wall synthesis. The bacterial cell wall contains peptidoglycan, a structure absent in human cells, making it an ideal target for selective toxicity. When antibiotics interfere with cell wall formation, bacterial cells become vulnerable and burst (lysis). This mechanism is particularly effective against actively growing bacteria. Other antibiotics inhibit protein synthesis by binding to bacterial ribosomes (70S), preventing translation of genetic information into proteins. Without proteins, bacteria cannot grow, divide, or carry out essential cellular functions.

All antibiotics act on only five specific targets in bacteria: (1) inhibiting cell wall synthesis (beta-lactamics, glycopeptides), (2) altering membrane permeability (polymyxins, daptomycin), (3) inhibiting protein synthesis (macrolides, aminoglycosides, tetracyclines), (4) inhibiting DNA synthesis (quinolones, rifampicin), and (5) interfering with metabolic processes (sulfonamides, trimethoprim). Despite the diversity of antibiotics, they all target these five fundamental bacterial processes. Cell wall synthesis inhibition prevents peptidoglycan formation, membrane permeability alteration causes leakage of cellular contents, protein synthesis inhibition blocks ribosomal function, DNA synthesis inhibition prevents replication, and metabolic interference disrupts essential biosynthetic pathways.

Antibiotics work through several mechanisms: (1) Cell wall synthesis inhibition - beta-lactams (penicillins, cephalosporins, carbapenems) and glycopeptides (vancomycin) attack bacterial cell walls; (2) Protein synthesis inhibition - targeting bacterial ribosomes (30S and 50S subunits); (3) Nucleic acid synthesis inhibition - quinolones and rifampicin (inhibits RNA polymerase); (4) Folate metabolism inhibition - sulfonamides and trimethoprim. Each mechanism targets specific bacterial structures or processes.