Microbial Genetics

Genes, Genomes, and Bacterial Chromosomes

Microbial genetics explores the structure, function, and transmission of genetic material in microorganisms. Understanding genes and genomes is fundamental to this field.

• Gene: A segment of DNA that encodes a functional product, usually a protein.

• Genome: The complete set of genetic material in an organism, including chromosomes and plasmids.

• Bacterial Chromosome: Typically a single, circular DNA molecule located in the nucleoid region of the cell.

• Plasmids: Small, circular, extrachromosomal DNA molecules that replicate independently and often carry genes for antibiotic resistance or other traits.

Example: Escherichia coli has a single circular chromosome and may carry several plasmids.

DNA Replication: Semiconservative Process

DNA replication ensures genetic information is accurately passed to daughter cells. The process is semiconservative, meaning each new DNA molecule contains one original and one new strand.

• Initiation: Begins at the origin of replication; helicase unwinds DNA, and primase synthesizes RNA primers.

• Elongation: DNA polymerase III adds nucleotides to the 3' end; leading strand is synthesized continuously, lagging strand in Okazaki fragments.

• Enzymes: DNA gyrase relieves supercoiling; ligase joins Okazaki fragments; DNA polymerase I replaces RNA primers with DNA.

Equation:

Transcription and Post-Transcriptional Modifications

Transcription is the synthesis of RNA from a DNA template, essential for gene expression.

• Initiation: RNA polymerase binds to the promoter with the help of sigma factors.

• Elongation: RNA polymerase synthesizes RNA in the 5' to 3' direction.

• Termination: Occurs at terminator sequences.

• Post-Transcriptional Modifications (Eukaryotes):

  • 5' capping

  • Poly-A tail addition (polyadenylation)

  • Splicing: Removal of introns, joining of exons

Example: Mature mRNA in eukaryotes has a 5' cap and a poly-A tail.

Translation and the Genetic Code

Translation is the process by which ribosomes synthesize proteins using mRNA as a template.

• Codon: A sequence of three nucleotides in mRNA that specifies an amino acid.

• Genetic Code: Universal set of codon-amino acid correspondences.

• Process:

  • Initiation: Ribosome assembles at the start codon (AUG).

  • Elongation: tRNAs bring amino acids to the ribosome; peptide bonds form.

  • Termination: Occurs at stop codons (UAA, UAG, UGA).

Example: Given DNA: ATG, mRNA: AUG, codes for methionine.

Mutations and Their Effects

Mutations are changes in the DNA sequence that can affect protein function and contribute to microbial evolution and drug resistance.

• Point Mutation: Single nucleotide change (substitution, insertion, deletion).

• Frameshift Mutation: Insertion or deletion that shifts the reading frame.

• Types: Silent, missense, nonsense mutations.

Example: A missense mutation changes one amino acid; a nonsense mutation introduces a premature stop codon.

Genetic Exchange in Bacteria

Bacteria can exchange genetic material through three main mechanisms, increasing genetic diversity and spreading traits like antibiotic resistance.

• Transformation: Uptake of naked DNA from the environment.

• Transduction: Transfer of DNA by bacteriophages (viruses that infect bacteria).

• Conjugation: Direct transfer of DNA via sex pili between bacterial cells (F+ to F-).

Example: Conjugation can transfer plasmids carrying antibiotic resistance genes.

Characterizing and Classifying Viruses, Viroids, and Prions

Structure of Virions

Viruses are acellular entities composed of genetic material and a protein coat, sometimes with an envelope.

• Virion: Complete, infectious virus particle.

• Capsid: Protein shell made of capsomeres.

• Envelope: Lipid membrane derived from host cell, present in enveloped viruses.

• Genetic Material: DNA or RNA, single- or double-stranded.

Example: Influenza virus is enveloped; adenovirus is nonenveloped (naked).

Viral Replication and Host Specificity

Animal viruses enter host cells by various mechanisms and replicate using host machinery. Replication strategies differ by genome type.

• Entry: Direct penetration, membrane fusion, or endocytosis.

• Replication:

  • ssRNA (+): Acts as mRNA.

  • dsDNA: Transcribed to mRNA.

  • Retroviruses: Use reverse transcriptase to make DNA from RNA.

• Release: Budding (enveloped), lysis (naked).

• Host Range: Determined by specific interactions between viral proteins and host cell receptors.

Example: HIV infects only human CD4+ T cells.

Obligate Intracellular Parasitism and Cultivation

Viruses require living cells for replication and are cultivated using cell cultures, embryonated eggs, or live animals.

• Obligate Intracellular Parasite: Cannot reproduce outside a host cell.

• Cell Culture: Continuous or diploid cell lines used for viral growth.

Example: Influenza virus is grown in embryonated chicken eggs for vaccine production.

Viral Pathogenesis and Cancer

Viruses can cause tissue destruction and some are associated with cancer (neoplasia).

• Latent Viruses: Remain dormant in host cells.

• Oncogenic Viruses: Can induce uncontrolled cell growth (e.g., HPV and cervical cancer).

Prions and Prion Diseases

Prions are infectious proteins that cause neurodegenerative diseases by inducing abnormal folding of normal proteins.

• Prion: Proteinaceous infectious particle (e.g., PrPSc).

• Diseases: Spongiform encephalopathies (e.g., Creutzfeldt-Jakob disease).

Infection, Infectious Diseases, and Epidemiology

Symbiosis and Normal Flora

Microbes interact with hosts in various symbiotic relationships, influencing health and disease.

• Mutualism: Both organisms benefit.

• Commensalism: One benefits, the other is unaffected.

• Parasitism: One benefits at the expense of the other.

• Normal Flora (Microbiome): Microorganisms that colonize the body without causing disease; provide microbial antagonism against pathogens.

Nature and Transmission of Infectious Diseases

Infectious diseases are caused by pathogenic microbes and can be transmitted by various routes.

• Reservoirs: Sources of infection (human, animal, nonliving).

• Portals of Entry/Exit: Sites where pathogens enter/leave the body (e.g., skin, mucous membranes).

• Modes of Transmission: Direct contact, indirect contact (fomites), droplet, airborne, vector-borne, waterborne, food-borne.

Example: Influenza spreads via droplet transmission.

Classification and Progression of Disease

Diseases are classified by duration, severity, and transmission. The progression includes several stages.

• Stages: Incubation, prodromal, illness, decline, convalescence.

• Types: Acute, chronic, latent, subclinical.

Virulence Factors and Pathogenicity

Virulence factors enhance a pathogen's ability to cause disease.

• Examples: Toxins (endotoxins, exotoxins), extracellular enzymes (collagenase, hyaluronidase), adhesins, capsules.

Epidemiology and Disease Occurrence

Epidemiology studies the distribution and determinants of diseases in populations.

• Incidence: Number of new cases in a given time period.

• Prevalence: Total number of cases at a given time.

• Endemic: Constantly present in a population.

• Epidemic: Sudden increase in cases.

• Pandemic: Worldwide epidemic.

Nosocomial (Hospital-Acquired) Infections

Nosocomial infections are acquired in healthcare settings and often involve antibiotic-resistant pathogens.

• Common Types: Urinary tract infections (CAUTI), pneumonia (HAP), bloodstream infections.

• Prevention: Hand hygiene, aseptic techniques, limiting catheter use.

• Pathogens: MRSA, VRE, MDR organisms.

Innate Immunity

Components of Nonspecific Defenses

Innate immunity provides immediate, nonspecific defense against pathogens.

• Physical Barriers: Skin, mucous membranes.

• Chemical Barriers: Lysozyme, sebum, dermcidins.

• Cellular Defenses: Leukocytes (neutrophils, macrophages, dendritic cells, natural killer cells).

Phagocytosis and Leukocytes

Phagocytosis is the process by which certain cells ingest and destroy microbes.

• Phagocytes: Neutrophils, macrophages, dendritic cells.

• Process: Chemotaxis, adherence, ingestion, digestion, exocytosis.

PAMPs and Toll-like Receptors (TLRs)

Pathogen-associated molecular patterns (PAMPs) are recognized by Toll-like receptors (TLRs) on immune cells, triggering immune responses.

• PAMPs: Conserved microbial molecules (e.g., LPS, flagellin).

• TLRs: Receptors that detect PAMPs and activate immune signaling.

Complement System

The complement system is a group of proteins that enhance immune responses.

• Activation Pathways: Classical, alternative, lectin.

• Functions: Opsonization, inflammation, membrane attack complex (MAC) formation.

Equation:

Interferons and Antiviral Defense

Interferons (IFN-α, IFN-β) are cytokines that inhibit viral replication and activate immune cells.

• Mechanism: Induce production of antiviral proteins in neighboring cells.

Inflammation and Fever

Inflammation is a localized response to infection or injury, characterized by redness, heat, swelling, and pain. Fever is a systemic response that inhibits pathogen growth.

• Chemicals Involved: Histamine, bradykinin, prostaglandins, leukotrienes.

• Fever: Triggered by pyrogens from pathogens or host cells.

Additional info: Some details, such as the full mechanisms of complement activation and the specifics of viral replication cycles, were expanded for academic completeness.