Medical Microbiology (lec5) PDF

Northern Technical University College of Health and Medical Techniques/ Kirkuk Medical Microbiology (lec5) By Ms. Noha Inam Ameen E. Mail : [email protected] 2025-2024  Bacterial Ge...

Northern Technical University College of Health and Medical Techniques/ Kirkuk Medical Microbiology (lec5) By Ms. Noha Inam Ameen E. Mail : [email protected] 2025-2024  Bacterial Genetics nucleic acid (DNA) that carries in its nucleotide sequence information for a specific biochemical or physiologic property. All hereditary properties are encoded in DNA. Hence, the chromosomal DNA plays an important role in the maintenance of character from generation to generation. Genetics is the study of heredity and variation to understand the cause of resemblance and differences between parents and their progeny. The unit of heredity is the gene, a segment of deoxyribo Genes carry the information to code for all the necessary components and the actions of life. The genes at each cell division are replicated and a copy is transmitted to each daughter cell.  Structure of DNA The DNA is the key basic component of gene, which carries the genetic information that is transcribed onto ribonucleic acid and then translated as the particular polypeptide. The DNA molecule is composed of two strands of complementary nucleotides bound together in the form of a double helix, as illustrated in the figure below. The basic building blocks of DNA are nucleotides, which are composed of a sugar group, a phosphate group, and a nitrogen base. The sugar and phosphate groups link the nucleotides together to form each strand of DNA. Purines (Adenine and Guanine), and pyrimidines (Thymine and Cytosine) are four types of nitrogen bases. These 4 Nitrogenous bases pair together in the following way: A with T, and C with G. These base pairs are essential for the DNA’s double helix structure, which resembles a twisted ladder. Gene It is a segment of DNA that carries codons specifying for a particular polypeptide. A DNA molecule consists of a large number of genes, each of which contains hundreds of thousands of nucleotides. The DNA of a bacterial chromosome is usually arranged in a circular form and when straightened, it measures around 1000 μ. The length of DNA is usually expressed as kilobases (1 kbp = 1000 base pairs, or bp). Structure of RNA Basically, the structure of RNA is similar to that of DNA except for two major differences: (a) In DNA, the sugar is deoxyribose; in RNA, the sugar is ribose. (b) The RNA contains the nitrogenous base Uracil instead of Thymine that is present in DNA.  On the basis of structure and function, the RNA can be differentiated into three types: (a) Messenger RNA (mRNA), (b) Ribosomal RNA (rRNA), and (c) Transfer RNA (tRNA). Codon is a trinucleotide sequence of DNA or RNA that corresponds to a specif ic amino acid. The genetic code describes the relationship between the sequence of DNA bases (A, C, G, and T) in a gene and the corresponding protein sequence that it encodes. There are 64 different codons: 61 specify amino acids while the remaining three are used as stop signals. The codon AUG is called the START codon as it the f irst codon in the transcribed mRNA that undergoes translation.  There are 3 STOP codons in the genetic code - UAG, UAA, and UGA. These codons signal the end of the polypeptide chain during translation. These codons are also known as nonsense codons or termination codons as they do not code for an amino acid. Plasmids Plasmids are extrachromosomal DNA substances. Plasmids are circular and double stranded DNA molecules that encode traits that are not essential for bacterial viability. They are capable of replicating independently of the bacterial chromosomes. The plasmids can also be present as integrated w it h b ac t erial c hromosomes, and p lasmid s int eg rat ed w it h host chromosome are known as episomes. Plasmids are present in both Gram- positive and Gram-negative bacteria. Types of plasmids Plasmids depending on their transmissibility can be of the following types: 1. Transmissible plasmids: They can be transferred from cell to cell by a process of genetic transfer known as conjugation. They contain more than a dozen genes responsible for synthesis of the sex pilus and for the synthesis of enzymes required for their transfer. Usually, one to three copies of the plasmid are present in a cell. 2. Nontransmissible plasmids: These cannot be transferred from cell to cell, because they do not contain the transfer genes. They depend on their bacterial host to provide some functions required for replication and are distributed randomly between daughter cells at division. Transmissible plasmids Another way to classify plasmids is by function. There are five main classes: Fertility F-plasmids, which contain genes. They are capable of conjugation and result in the expression of sex pilli.-1 Resistance plasmids, which contain genes that provide resistance against antibiotics or poisons. They were known as R-factors, before the nature of plasmids was understood.-2 Col plasmids, which contain genes that code for bacteriocins, proteins that can kill other bacteria.-3 Degradative plasmids, which enable the digestion of unusual substances, e.g. toluene and salicylic acid.-4 Virulence plasmids, which turn the bacterium into a pathogen-5  Northern Technical University College of Health and Medical Techniques/ Kirkuk Medical Microbiology (lec6) By Ms. Noha Inam Ameen E. Mail : [email protected] 2025-2024  Mutations Mutation is a random, undirected, and heritable variation seen in DNA of the cell. This is caused by a change in base sequence of DNA due to addition, deletion, or substitution of one or more bases in the nucleotide sequence of DNA. It can involve any of the genes present in the bacterial chromosome. Mutation results in insertion of a different amino acid into a protein, resulting in the appearance of an altered phenotype. Types of Mutations Mutations are a natural event occurring in dividing cells. The frequency of mutations ranges from 10−2 to 10−10 per bacterium per division. These occur spontaneously or are enhanced by different mutagens. Mutations are 2 types: Small DNA Alterations or Large DNA Alterations.  Small DNA Alterations A mutation involving a change in a single base pair, often called a point mutation, or a deletion or insertion of a few base pairs generally affects the function of a single gene. 1. Point mutation is a change in a single nucleotide in DNA. An example of a point mutation is a mutation that changes the codon UUU to the codon UCU. Point mutations can be silent, missense, or nonsense mutations, as shown in the following table. The effects of point mutations depend on how they change the genetic code.  2. Frameshift Mutations A frameshift mutation is a deletion or insertion of one or more nucleotides that changes the reading frame of the base sequence. Deletions remove nucleotides, and insertions add nucleotides. As reading frame is a way of dividing the sequence of nucleotides in a nucleic acid (DNA or RNA) molecule into a set of consecutive, non-overlapping triplets. Consider the following sequence of bases in RNA: AUG-AAU-ACG-GCU = start-asparagine-threonine-alanine Now assume that an insertion occurs in this sequence. Let’s say an A nucleotide is inserted after the start codon AUG. Then the sequence of bases becomes: AUG-AAA-UAC-GGC-U = start-lysine-tyrosine-glycine Even though the rest of the sequence is unchanged, this insertion changes the reading frame and thus all of the codons that follow it. As this example shows, a frameshift mutation can dramatically change how the codons in mRNA are read. This can have a drastic effect on the protein product. Another example of the frameshift mutation due to the deletion of a nucleotide is illustrated in the f ig ure below. In this example, a premature stop codon is created by the mutation Large DNA Alterations The second major type of mutation involves large-scale changes in chromosome structure and can affect the functioning of numerous genes, resulting in major phenotypic consequences. Such chromosomal mutations (or abnormalities) can involve deletion or insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange of large segments of DNA between nonhomologous chromosome. Causative Agents of Mutation Mutation can be caused by (a) viruses, (b) radiation, or (c) chemicals. (a) Viruses Bacterial viruses (mutator bacteriophage) are an example of viruses that cause a high frequency of mutation by inserting their DNA into the bacterial chromosome. Mutations can occur in various genes as viral DNA can insert bacterial chromosome at many different sites. (b) Radiations X-rays and ultraviolet light are the examples of radiation that can cause mutation in chromosomal DNA.  X-rays: X-rays damage DNA in many ways. They cause damage by producing free radicals that can attack the bases or alter them in the strand, thereby changing their hydrogen bonding. They also damage DNA by breaking the covalent bonds that hold the ribose phosphate together. Ultraviolet light: Ultraviolet radiation causes damage in DNA by cross linking of the adjacent pyrimidine bases to form dimers. For example, the cross-linking of adjacent thymine to form thymine dimers results in the inability of DNA to replicate properly. (c) Chemicals Various chemicals, such as nitrous acid, alkylating agents, benzpyrene, and base analogs, such as 5-bromouracil cause mutation in several different ways: Benzpyrene: by binding to existing DNA bases and causes frame-shift mutations. The benzpyrene, which is a carcinogen as well as a mutagen, intercalates between the adjacent bases, thereby distorting and offsetting the nucleotide sequence in the DNA. Nitrous acid and alkylating agents: They act by altering the existing base in the DNA. This results in formation of a hydrogen bond with a wrong base. For example, adenine does not form bond with thymine but makes wrong pair with cytosine. Base analogs: Base analogs, such as 5-bromouracil, have less hydrogen bonding capacity than thymine, so they bind to guanine with better frequency. This results in a mutation due to a transition from AT base pair to a GC base pair. Effects of Mutations Mutations in the bacteria cause a lot of changes in their various properties. Mutation alters drug susceptibility, antigenic structure, and virulence of mutant bacteria. It also alters susceptibility of bacteria to bacteriophages, alter their colony morphology and pigment productions, and affect their ability to produce capsule or flagella. Genes transfer in Bacteria In bacterial population DNA can be transferred from one organism to another by the horizontal transfer mechanism (apart from vertical inheritance). The DNA thus transferred by lateral/horizontal method can be stably incorporated in the recipient, and changes the genetic composition of recipient permanently. Three broad mechanisms mediate efficient movement of DNA between cells- conjugation, transduction and transformation. Conjugation: Transfer of genes between cells that are in physical contact with one another.- Conjugation requires donor cell-to-recipient cell contact and is mediated by sex pilus- Process occurs between two living cells- Plasmid are genetic elements most frequently transferred by conjugation- Transduction: Transfer of genes from one cell to another by a bacteriophage- Phage mediated genetic recombination in bacteria i.e. phage is used to transfer DNA from one bacterium to another- There are two broad categories of Transduction- - Generalized transduction: Where virtually any genetic marker can be transferred - Specialized transduction: Bacterial DNA who are adjacent to viral DNA in the prophage get transferred Transformation: Transfer of cell-free or “naked” DNA from one cell to another.- Recipient cell uptake free DNA released into the environment.- DNA is released it to the environment when another bacterial cell (i.e. donor) dies and undergoes lysis- Not all bacteria are able to go for transformation, only some bacteria are able to take free DNA and are able to go transformation. These type of bacterial are called competent bacteria.-