MICR20010 Lecture 7 2024 - Bacterial Genetics PDF

MICR20010 Lecture 7 Bacterial Genetics Dr. Jennifer Mitchell Microbiology School of Biomolecular and Biomedical Science  Lecture 6 Metabolic diversity Chemical basis of energy production Simplified model of energy production Energy stor...

MICR20010 Lecture 7 Bacterial Genetics Dr. Jennifer Mitchell Microbiology School of Biomolecular and Biomedical Science  Lecture 6 Metabolic diversity Chemical basis of energy production Simplified model of energy production Energy storage and release Chemotrophs Phototrophs Chemotrophs – Chemoorganotrophs – Chemolithotrophs Autotrophs Heterotrophs Photosynthesis Learning Outcomes DNA DNA replication Gene structure – Transcription Protein synthesis – Translation Antibiotics The Genetic Code Mutation Genetic Exchange  DNA Deoxyribonucleic Acid (DNA) Monomer building blocks called deoxyribonucleotides: – 5-carbon sugar deoxyribose – a nitrogenous base – a phosphate group 5 4 1 3 2  Bases 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≡C G≡C  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 Proofreading Termination  DNA Polymerase DNA polymerase can 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 only a preexisting 3'-OH group 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 molecules to specify the exact sequence of amino acids in a 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 can lead to bacterial resistance 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. Highlights bacterial adaptability. Transmission of AMR genes between species Mutation 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 0157)  Mutagenesis Mutagens Physical - Radiation Chemical mutagenesis – Base analogues – Intercalating agents – Metals - ROS Biological agents – Virus – Transposon 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  Conjugation 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 Plasmids replicate in the donor cell prior to transfer into the recipient cell  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 genomic DNA is also packaged  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 facilitated rapid dissemination of antibiotic resistance genes among different bacterial species  Genetic Variation and Antibiotic Resistance Mutation – (e.g. drug resistance in tuberculosis) Transformation/transposition – (e.g. Penicillin-resistant gonorrhea) Conjugation – (e.g. multi-resistant shigella)  Further Reading Brock Biology of Microorganisms Chapter 10 “Bacterial Genetics”