Microbial Genetics PDF

Microbial Genetics Microbiology and Immunology – NURS1008 Assistant Prof. Amira ElBaradei Microbiology and Immunology Department College of Medicine and Health Sciences...

Microbial Genetics Microbiology and Immunology – NURS1008 Assistant Prof. Amira ElBaradei Microbiology and Immunology Department College of Medicine and Health Sciences Sultan Qaboos University Sultan Qaboos University © College of Medicine and Health Sciences Objectives: Review the nature of genetic elements of bacterial Know and understand the mechanisms by which genetic changes occur in micro-organisms Understand microbiological and clinical significance of Microbial genetic variations and its application. Sultan Qaboos University © College of Medicine and Health Sciences  Microbial genetics: It is the study of the mechanisms of heritable information in microorganisms, including bacteria, archaea, viruses and some protozoa and fungi. Sultan Qaboos University © College of Medicine and Health Sciences Bacterial Genetic Elements: Chromosome Plasmids Sultan Qaboos University © College of Medicine and Health Sciences Chromosome: Bacterial chromosomes are typically circular, double-stranded DNA molecules. They carry essential genetic information for the bacterium's survival and function. They contain genes responsible for metabolism, growth, and reproduction. Sultan Qaboos University © College of Medicine and Health Sciences Plasmids: Plasmids are small, circular, extrachromosomal DNA molecules found in bacteria. Smaller than bacterial chromosome Non-essential for bacterium survival They are separate from the chromosomal DNA and can replicate independently. Sultan Qaboos University © College of Medicine and Health Sciences Plasmids: Carry genes for accessory traits (Generally do not encode essential genes). Usually confer antibiotic resistance Plasmid size: 1 - 250 kbp. Plasmid copy number per cell: 1 - 100 A bacterium may have multiple copies of same plasmid, or different plasmids Occur in bacteria & in some eukaryotes (e.g. yeasts) Sultan Qaboos University © College of Medicine and Health Sciences  Genetic variation in microorganisms Mutation Recombination Sultan Qaboos University © College of Medicine and Health Sciences Mutation: The word “mutation” is derived from the Latin verb “mutare”, which means to move or to change. Definition: It is an alteration (change) in the nucleotide sequence of a cell’s DNA. Effects: In most cases, mutations lead to harmful changes but beneficial changes may occur. Mutations are the main sources of biological diversity. Sultan Qaboos University © College of Medicine and Health Sciences Mutation According to origin: 1. Spontaneous mutations 2. Induced mutations Mutation According to origin: 1. Spontaneous mutations They are natural occurring mutations during replication. They are not caused by external agents. These arise naturally due to errors during replication. Mutation According to origin: 2. Induced mutations They are caused by external agents that chemically alter DNA, usually causing a form of DNA damage. Induced by physical or chemical means. Mutagens or mutagenic agents are physical and chemical factors which increase mutation rates. Mutagens can be divided into 2 general classes: - Radiation - Chemical mutagens Classification of Mutation: According to size: 1. Gross mutations: Changes involving large sections of DNA May involve entire genes 2. Point mutation: A change in a very small segment of DNA; usually involves a single nucleotide It is subdivided into: A. Substitution mutations B. Frame-shift mutations Sultan Qaboos University © College of Medicine and Health Sciences Mutation Types of mutation: - Frameshift mutations (insertion/deletion ) - Base substitutions (Substitution mutation) A. Substitution mutation: It can be further divided into: A. Substitution mutation: It is the substitution of one nucleotide by another. It can be further divided into: i. Missense mutation ii. Same-sense (silent) mutation iii. Nonsense mutation Sultan Qaboos University © College of Medicine and Health Sciences Mutations I. Missense Mutations is a mutation that changes the codon and causes a change in the amino acid sequence of a gene’s product. It leads to a change in the translated amino acid. II. Same-sense (silent) Mutation is a mutation that changes the codon but fails to change the amino acid. It alters a codon but does not result in a change in the amino acid. Sultan Qaboos University © College of Medicine and Health Sciences Mutations III. Nonsense Mutation changes a codon into a stop codon and results in premature termination of translation. Which means it causes shortening of the protein product due to a chain termination. Sultan Qaboos University © College of Medicine and Health Sciences b. Frame-shift mutation Frame-shift mutation can be further divided into: i. Deletion mutation ii. Insertion mutations Both insertion and deletion cause frameshift in the ORF because they shift the reading frame of the genetic message. Sultan Qaboos University © College of Medicine and Health Sciences Frame-shift mutation Deletion mutation: Insertion mutations: loss of some portion of a gene. addition of one or more extra nucleotides to a gene. Recombination “GENE TRANSFER” Recombination involves the exchange of genetic material between different DNA molecules. Recombination events can result in the acquisition of new traits or the transfer of genetic material, such as antibiotic resistance genes. Sultan Qaboos University © College of Medicine and Health Sciences Genetic reassortment Reassortment is a form of genetic recombination in viruses. Genetic reassortment, the mixing of genes between two organisms to make a new genetic sequence known as a recombinant, is a powerful mechanism for evolution and adaptation. This reassortment occurs typically when two different influenza viruses infect the same host. Yeo, Joshua & Gan, Samuel Ken-En. (2021). Peering Into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness. 10.20944/preprints202109.0506.v1. Recombination “GENE TRANSFER” The acquisition of new segments of DNA There are three ways in which new genes may be acquired by a bacterial cell: Conjugation Transduction Transformation Sultan Qaboos University © College of Medicine and Health Sciences A) Transformation Genetic recombination in which a DNA fragment from a dead, degraded bacterium enters a competent recipient bacterium and it is exchanged for a piece of the recipient's DNA. Sultan Qaboos University © College of Medicine and Health Sciences Transformation 2. A fragment of DNA from the dead donor bacterium binds to DNA binding proteins on the cell wall of a competent, living 1. A donor bacterium dies and is degraded recipient bacterium 3. The Rec A protein promotes genetic exchange 4. Exchange is complete between a fragment of the donor's DNA and the recipient's DNA B) Transduction The transfer of bacterial DNA is transferred from one bacterium to the other by with the help of a phage. A virus that infects bacteria, called a bacteriophage or a phage. Structure of T4 bacteriophage Sultan Qaboos University © College of Medicine and Health Sciences C) Bacterial Conjugation Conjugation differs from transformation in two major ways. 1- conjugation requires direct cell-to- cell contact. 2- the conjugating cells must generally be of the opposite mating type, donor cells must carry the plasmids, recipient cells normally do not. Donor bacterial cells have surface structure called F-pilus (F+) It transfers its genetic material to recipient (F-) bacterium Sultan Qaboos University © College of Medicine and Health Sciences Microbiological and clinical significance of microbial genetic variations and applications: Antibiotic Resistance Virulence Factors Biotechnology Sultan Qaboos University © College of Medicine and Health Sciences Antibiotic Resistance: The acquisition of resistance genes via plasmids or the development of antibiotic resistance due to mutations, pose a significant challenge in clinical settings. Understanding the mechanisms of resistance helps in developing strategies to combat antibiotic resistance. Sultan Qaboos University © College of Medicine and Health Sciences Virulence Factors: Genetic variations in microbial pathogens can lead to changes in virulence, influencing the severity of infections. Studying these variations helps to in developing targeted therapies. Sultan Qaboos University © College of Medicine and Health Sciences Biotechnology: Biotechnology: is technology that utilizes biological systems, living organisms or parts of this to develop or create different products. For example, the commercial production of proteins for medicine and other industrial purposes. - the production of pharmaceuticals (such as insulin) Sultan Qaboos University © College of Medicine and Health Sciences Viral vectors When viruses are genetically modified to deliver and express whether their own or foreign genes, they are called virus vectors. Viral vectors are designed for different objectives, including: - Vaccination against specific diseases - Gene therapy in animals or humans usually to replace deficient genes - Anticancer agents that specifically kill tumour cells Gene therapy Gene therapy is the transfer of genetic material into cells in order to treat diseases. Gene therapy is a genetic-based treatment that can be used to treat inherited diseases. There are several approaches to gene therapy - Viral vectors (example Adenoviruses) - Non-viral gene delivery systems Sultan Qaboos University © College of Medicine and Health Sciences  Thank you Sultan Qaboos University © College of Medicine and Health Sciences