MICR20010 Lecture 7 2023.pptx

MICR20010 Lecture 7 Bacterial Genetics Dr. Jennifer Mitchell Microbiology School of Biomolecular and Biomedical Science Lectur e6 • Metabolic diversity • Chemical basis of energy production • Simplified model of energy production • Energy storage and release • Chemotrophs • Phototrophs • Chemotro...

MICR20010 Lecture 7 Bacterial Genetics Dr. Jennifer Mitchell Microbiology School of Biomolecular and Biomedical Science Lectur e6 • Metabolic diversity • Chemical basis of energy production • Simplified model of energy production • Energy storage and release • Chemotrophs • Phototrophs • Chemotrophs – Chemoorganotrophs – Chemolithotrophs • Autotrophs • Heterotrophs Learning Outcomes • DNA • DNA replication • Gene structure – Transcription • Protein synthesis – Translation • Antibiotics • The Genetic DNA • Deoxyribonucleic Acid (DNA) • Monomer building blocks called deoxyribonucleotides: – 5-carbon sugar deoxyribose – a nitrogenous base – a phosphate group 5 1 4 3 2 Bas es • There are four nitrogenous bases found in DNA – Adenine (A) – Guanine (G) – Cytosine (C) – Thymine (T) DNA strand DNA • DNA consists of two complementary strands (double stranded) • Complementary base pairing A= T G≡ CG DNA Replication • The process of generating an identical set of genes during cell division • Very accurate process carried out by DNA polymerases • Occasional inaccuracies give rise to a slightly altered nucleotide sequence – a mutation DNA Replication • Initiation • Elongation • Proofreadi ng • Terminatio n DNA Polymerase polymerase can • DNA add free nucleotides to only the 3' end of the newly-forming strand. • This results in elongation of the new strand in a 5'3' direction. • No known DNA polymerase is able to begin a new chain (de novo). • DNA polymerase can add a nucleotide onto DNA strand Genetic Code • DNA contains the genetic information (genes) required for all cellular processes • Genes can occur individually or in groups (operons) Gene Expression: Transcription • Initiated at the promoter region upstream of the gene • RNA polymerase copies the DNA and produces an RNA transcript (mRNA) Translation • mRNA is decoded by ribosomes and tRNA Gene Structure Protein Expression The Genetic Code • Codon • A set of three adjacent nucleotides that encode a particular amino acid. • Specifying the type and sequence of amino acids for protein synthesis. Antibiotics and DNA/RNA/Protein • Some antibiotics target DNA replication, transcription and translation • Rifampicin affects RNA polymerase • Macrolides (erythromycin), Kanamycin, Tetracycline affect ribosome & protein synthesis • Mutations in the antibiotic target Ciprofoxacin • Ciprofoxacin targets DNA gyrase, the enzyme which unwinds bacterial DNA during replication. • Ciprofoxacin prevents cell division • Quinolone antibiotic Plasmids • Circular extrachromosomal DNA • Replicate independently and can move between cells • Phenotypic advantage for the host cell • Plasmid genes: – Antibiotic resistance genes (often multiple) – Virulence genes (e.g. toxins) – Metabolic genes Hospital-acquired Infections • Plasmids with multiple antibiotic resistance genes predominate within hospital bacteria • Infections caused by such bacteria (nosocomial or hospital-acquired infections) are therefore particularly serious and difficult to treat. • Antibiotic resistance genes existed before the era of antibiotic treatment but have become prevalent due to selective pressure. Transmission of AMR genes between species Mutati on • Most common source of genetic variation • Spontaneous or induced (mutagens) • Three types – Substitution – Deletion – Insertion Codons - Mutation Genetic Variation • Important implications for microbial virulence: • Resistance to antibiotics • New virulence factors (e.g. E. coli Mutagenesis Mutagens • Physical Radiation • Chemical mutagenesis – Base analogues – Intercalating agents – Metals - ROS • Biological agents Genetic Exchange • Modes of Genetic Transfer between Bacterial Cells Transformation • DNA fragments can be taken up directly by bacterial cells • Normally degraded • Sometimes integrated into host genome • Some bacteria are naturally competent e.g. Streptococcus pneumoniae Conjugat ion • Describes plasmid transfer between bacterial cells • Requires cell-to-cell contact & can occur between different bacterial species and even between G+ve and G-ve • tra genes encode pilus (channel) between the cells through which the plasmid moves Transduction • DNA transfer between bacteria via infection with a bacteriophage • Phage infect the bacterial cell and replicate • Involves incorporation of phage DNA into phage capsids (heads) • Occasionally host Transposition • Transposons are DNA sequences that can ‘jump’ within the bacterial genome and from the genome to plasmids within the same cell • Transposons carry the enzymes required for their own transposition (homology not needed). This can result in gene disruption • Transposons often contain antibiotic resistance genes • Transposition into broad host range plasmids has Genetic Variation and Antibiotic Resistance • Mutation – (e.g. drug resistance in tuberculosis) • Transformation/ transposition – (e.g. Penicillin-resistant gonorrhea) • Conjugation Further Reading • Brock Biology of Microorganisms • Chapter 10 “Bacterial Genetics”