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Pharmaceutical Microbiology

• This course explains concepts of Quality Control and Quality Assurance in the pharmaceutical industry
• The course also teaches microbial production, assay methods, and aseptic lab techniques
• Students will learn to identify micro-organisms from products, evaluate antimicrobial effectiveness of substances and analyze the effectiveness of antibiotics.

Introduction to Microbiology

• Microbiology studies microorganisms, which are minute living bodies like bacteria or viruses, not visible to the naked eye
• Pathogenic microorganisms transmit from one host to another in several ways
• Animal sources: Direct, indirect, or intermediary animal hosts can transmit pathogenic organisms to humans and animals
• Airborne: Microorganisms discharged from the respiratory tract settle on food, dishes, or clothing
• Contact infections: Bacteria transmit directly from host to host, for example, sexually transmitted diseases (STD).
• Foodborne: Pathogenic organisms contaminate food and water by infected persons or faecal/insect contamination
• Fomites: Inanimate objects such as books, cooking utensils, or clothing that harbor microorganisms can transport them
• Human Carriers: Those who have recovered from an infectious disease remain carriers of the organism
• Insects: Insects act as physical carriers, like houseflies, or intermediate hosts, for instance, the Anopheles mosquito.
• Soilborne: Spore-forming organisms enter the body through cuts or wounds
• Fruits and vegetables, especially root and tuber crops, need thorough cleansing before consumption
• Microbiology investigates microbes, which can be unicellular or multicellular, existing in plants, animals, air, water, soil, and marine environments

Classification of Micro-organisms

• Taxonomy organizes, classifies, and names living things based on specific criteria; each organism is placed into a classification system
• It is based on Domain, Kingdom, Phylum, Class, Order, Family, Genus, or species
• The three Domains are Eubacteria, Archaea, and Eukarya
• Eubacteria are true bacteria, possess peptidoglycan
• Archaea are bacteria in extreme conditions
• Eukarya possess a nucleus and organelles like protists, fungi or algae

Domains

• Eukaryotes are organisms with a nucleus, a nuclear membrane, and cytoplasm with self-replicating organelles
• Prokaryotes Bacteria lack a true nucleus and internal membranes, have a rigid cell wall, reproduce by binary fission, possess DNA and RNA, have metabolic enzymes, are visible under a light microscope, and cannot pass through a 0.2 micrometer membrane
• Examples of Prokaryotes are Bacteria, rickettsia, and chlamydia.
• Akaryocytes do not have nuclei, and their name derives from Greek prefixes meaning "without nut or kernel."
• Akaryocytes include viruses; they are not part of the seven main ranks of taxa
• A capsid encapsulates the viral genome for protection, attachment, and stability
• Viruses have no metabolism, depend on the host cell for replication, and possess either DNA or RNA genomes but lack ribosomes

Viral genomes encode information for replication, viral protein production, and subverting cellular functions for virion production

Some viruses infect prokaryotic or eukaryotic cells, destroy cells, or persist in a latent/persistent state, causing cellular transformation

Structure and Function of Microorganisms

• Viruses consist of a nucleic acid genome and a protein coat, an external membrane called an envelope

• Icosahedral viruses have their genetic material enclosed inside the capsid. These virions are released when the cell dies, breaks down and lyses

poliovirus, rhinovirus, and adenovirus are icosahedral

• Enveloped viruses have a helical core surrounded by a lipid bilayer membrane; virus exits the cell via budding and infectivity depends on the envelope

• Examples of enveloped viruses are influenza virus, Hepatitis C and HIV

• Complex viruses combine icosahedral and helical shape and can have a complex outer wall/head-tail morphology; bacteriophages are examples, infecting only bacteria.

• Helical viruses possess a capsid with a central cavity/hollow tube of proteins arranged circularly, creating a disc-like shape Examples includes tobacco mosaic virus.

Viral Entry

• Virus receptors are host cell surface components that viruses recognize as a gateway to cell entry
• Ideal virus receptors exhibit physical interaction with the virus, inhibit virus infection when occupied, and correlate cellular sensitivity with receptor expression
• CD4 transmembrane protein: Expressed by human T-lymphocytes, it's a key receptor for HIV-1.
• Cellular protein TIM-1: Acts as a receptor for Ebola virus and Marburg virus

Viral and Bacterial Life Cycles

• Life cycles of microorganisms include events during viral and bacterial life cycles.

Ecological Relationships

• Ecological relationships include microbial interactions, host-parasite interactions, and effects of the environment
• The triad consists of an external agent, a susceptible host, and an environment that bring the host and agent together
• Diseases result from the interaction between the agent and the susceptible host in an environments that supports the agent's transmission from a source to that host

Acquiring Infectious Agents

• Infectious agents enter/exit the body via several portals
• Ingestion
• Inhalation:
• Direct penetration: Trauma, surgery, needles, arthropods, sex, transplacental
• Colonization is the successful occupation of a new habitat by a species not normally found there
• Adherence (attachment) involves close association of bacterial cells and host cells through receptors on target sites
• Adhesin is a structure/macromolecule on a cell's surface or extracellularly that helps adherence to a surface or another cell and can be specific or nonspecific like Lectin
• Invasion occurs when an infecting agent enters and spreads throughout the host's cells and/or tissues, pathogenic advantage is enhanced
• Invasins (invasive factors) are structures/macromolecules that help invasion by pathogenic microorganisms.
• Multiplication is ability of a microorganism to reproduce during an infection and may be influenced by immunologic status, antibiotic treatment, or nutrient availability

Disease Transmission

• Transmission of disease depends upon entrance, colonization, penetration and the host's age, sex, nutrition, immunologic state and virulence.
• Vectors are carriers, often animals, that transmit infectious agents, usually arthropods from one host to another.
• Carriers are symptomless individuals host to a pathogenic micro-organism with the potential to infect others
• Nosocomial infections are acquired in a hospital setting, not present before admission, and occur generally occurring within 72 hours.

Pathogenicity vs. Virulence

• Pathogenicity is the quality of producing disease or the ability to produce pathologic changes or disease
• Virulence measures pathogenicity or the degree of disease-producing ability based on the intensity of the disease
• Virulence may be measured by the dosage needed to cause a specific degree of pathogenicity
• One general standard is the LD50 (lethal dose 50%), which is the dose required to kill 50% of a population

Bacterial Virulence Mechanisms

• Adherence (Colonization)
• Invasion
• Degradative enzymes
• Exotoxins
• Endotoxin
• Induction of excess inflammation refers to an inflammatory response that is disproportionately strong, often leading to tissue damage. This process may occur due to pathogens releasing inflammatory mediators or through the host's immune response being excessively activated, causing chronic inflammation, which can contribute to various diseases such as autoimmune disorders and chronic inflammatory conditions. Such responses can significantly affect the host's health and recovery from infections.
• Evasion of phagocytic & immune clearance
• Byproducts of growth (gas, acid)
• Superantigen
• Resistance to antibiotics

Infection and Disease

• Infection: Colonization, invasion, multiplication of pathogenic microorganisms in host.
• Disease: Abnormal condition harmful to the affected individual; deviation/interruption of normal structure/function
• Benign conditions are neither life nor health-threatening scenarios
• Malignant diseases worsen over time (morbidity=illness) and lead to death.
• Contagious infections are communicable from one host to another
• Infectious dose is the amount of pathogenic organisms required to cause disease in a host

Koch's Postulates

• Robert Koch developed four criteria to identify a disease's causative agent:
• The microorganism must be present in all cases of the disease
• The pathogen can be isolated from the diseased host and grown in pure culture
• The pathogen from the pure culture must cause the same disease when inoculated into a healthy, susceptible laboratory animal
• The pathogen must be reisolated from the new host and show the same characteristics as original pathogen
• Pathogenicity is dependent on understanding of pathogens, host susceptibility, the interaction between host and pathogen, reservoir hosts, modes of pathogen shedding and transmission routes
• Pharmaceutical Microbiology focuses on the use of microorganisms in pharmaceutical development and maintaining contamination control
• Pharmaceutical microbiology encompasses health care, infection control, possible contaminants and good manufacturing practices