Introduction to Infection and Pharmaceutical Microbiology

What are the three main types of microbes?

Viruses, fungi (and other microscopic eukaryotes) and bacteria. Viruses are not cellular. Fungi/other microscopic eukaryotes/bacteria are cellular

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Can microbes be seen by the naked eye?

No - microscopy is needed to see individual microbes

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What are the two classes of microscope?

Light and electron. Electron microscope uses a beam of electrons to create an image. Capable of higher magnifications/greater resolving power than LM, see smaller objects in finer detail

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What are the relative sizes of cells which can be viewed with an EM?

1 angstrom to 100 microns

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What are the relative sizes of cells which can be viewed with an LM?

500 microns to ~ 2mm

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Describe features of viruses

All grow in cells. Classed as infectious agents. Many different viral pathogens, all have small genomes (few antiviral agents)

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Give examples of viruses

Some cause common colds (e.g. rhinoviruses). Others are more of a clinical concern e.g. influenza and herpes virus. Certain viruses rare in human populations/dangerous pathogens e.g. ebola virus

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What are the concerns about viruses? (1)

Potential for rapid spread. Potential for high fatality rate and often a lack of treatment options (e.g. nipah virus causes illness/inflammation of brain/respiratory disease, no treatment)

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What are the concerns about viruses? (2)

Significant problem if traits combine (localised/severe infections, worldwide spread potential)

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Describe features of fungi and microscopic eukaryotes

All eukaryotic cells have a nuclear membrane. Cell 'machinery' is like human cells. Harder to treat by antimicrobial agents. Many form resting stages or spores (more difficult to deal with)

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Describe features of fungi

Grow as single cells (yeast) or as long branches (hyphae). Some fungi are dimorphic - can grow as either yeasts or hyphae

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Which fungi has the most clinical concern?

Candida albicans. Aspergillus fumigatus. Invasive infections/immunocompromised. Number of invasive fungal infections increasing in the UK

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Describe features of other (non-fungal) microscopic eukaryotes

Parasites, primarily protozoa. E.g. Plasmodium falciparum which causes the most dangerous form of malaria. Complex life cycle (vector/mosquito). Solutions (anti-microbial/anti-vector)

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What is the effect of climate change on tropical diseases?

Climate change could lead to change in infection problems and a growing threat of mosquito borne diseases e.g. fatal malaria in the UK

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Describe features of bacteria (1)

Biggest clinical problem. Bacterial/archaeal cells are prokaryotes. Differ from eukaryotes (lack nuclear membrane). Grow as single cells outside human cells. Over 35,000 species (100s can be human pathogens), over 1000 genes

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Describe features of bacteria (2)

Divided into Gram + and Gram - cell types. Reflects different cell wall structures. Detected by chemical staining

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Describe the differences between the two wall types for bacterial cells

Gram positive cell wall (thick layer of peptidoglycan with lipoteichoic acid) e.g. Staphylococcus aureus. Gram negative cell wall (thin layer of peptidoglycan, outer membrane layer/difficult to get past barrier) e.g. Escherichia coli

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What is taxonomy and nomenclature? (1)

All living organisms (e.g. not viruses) classified into a structure from Domain level to species level. Have two names, first as a genus name, second as a species name. Life, domain, kingdom, phylum, class, order, family, genus, species

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What is taxonomy and nomenclature? (2)

Bacterial species, named on their phenotype, isolation source or honouring someone. Below species level are strains. Contrasting E.coli O157:H7 with E.coli Nissle 1917

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What is the taxonomy and nomenclature for humans?

Eukarya, animalia/metazoa, chordata, mammalia, primates, hominidae, homo, homo sapiens

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What is the taxonomy and nomenclature for Staphylococcus aureus?

Bacteria, firmicutes, bacilli, bacillales, staphylococcaceae, staphylococcus, staphylococcus aureus

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What is the taxonomy and nomenclature for Escherichia coli?

Bacteria, proteobacteria, gamma-proteobacteria, enterobacteriales, enterobacteriaceae, Escherichia coli

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Describe features of bacterial resistance (1)

Infections by certain species such as Staphylococcus aureus in pneumonia cause clinical concern because they can lead rapidly to mortality (days). Resistance to antimicrobial agents makes certain species difficult to treat

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Describe features of bacterial resistance (2)

e.g. MRSA, Pseudomonas aeruginosa, Mycobacterium tuberculosis, clostridium difficile, Gram-negative cells that have extended spectrum beta lactamase resistance mechanisms

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Describe features of bacterial resistance (3)

Bacterial resistance to antimicrobial agents is a real problem. Direct consequence of resistance in terms of additional mortality arising from MRSA infection in England and Wales

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What is a practical problem with bacterial species?

Bacterial species produce spores (resting stages for bacterial cells). Normal cells grow out of spores (desporulation). Spores remain dormant for years (hard to destroy)

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Give examples of spore-forming bacterial species

Clostridium difficile (main clinical concern). Bacillus anthracis (anthrax) - bioweapon

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Describe features of microbes and infections

Each class of microbe (virus, fungus, parasite, bacteria) has members that can cause human infection. Some infections cause more clinical concern than others. E.g. TB infection (need to consider why microbes are abundant)

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Describe the abundance of microbes

10^30 cells in soil and water in the natural environment. Microbes in built environment (some from natural environment, some from us). Pathogens remain viable from varying times on surfaces and in the air. Potential problem (spread of infection)

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Describe features of bacteria in the human body

High number of bacterial cells in the human body. Every body contains 10^14 cells (1.3 kg of microbes). Main locations - oral cavity and upper respiratory tract, skin, gastro-intestinal tract (>90% of human associated microbes)

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Why is bacteria so abundant? (1)

Bacterial species can grow rapidly e.g. cell division can be every 20 mins, large populations can be achieved quickly

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Why is bacteria so abundant? (2)

Different species have diverse physiologies (extremes, growth possible e.g. temperatures -5 to 120 degrees Celsius, pH 1-11, anaerobic/aerobic environments). Bacteria exploit many different habitats through diverse physiologies

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Why is bacteria so abundant? (3)

Diverse physiologies result form diversity of genes (functions) carried in bacterial genomes. Some functions provide a way for microbes to resistant an antimicrobial agent. Genes encoding these functions can move from species to species

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Why is bacteria so abundant? (4)

Microbes are diverse and widespread. Implication - unless we do something about it, all surfaces (biotic, abiotic) and substances have microbes (can lead to infection, product spoilage). Need to develop antimicrobial strategies

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Describe features of developing antimicrobial strategies (1)

Pharmaceutical preparation (microbes present, obvious potential for cause infection, microbial modification/spoilage of drug itself, methods needed to make microbe free preparations)

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Describe features of developing antimicrobial strategies (2)

Managing microbes (environments e.g. hospital, impractical to be free of microbes, need method to manage microbes within defined limits)

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Describe features of developing antimicrobial strategies (3)

Infections in/on body (there are beneficial bacteria as well as pathogen trying to treat, need method to deal with pathogen only)

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Describe features of developing antimicrobial strategies (4)

Pharmaceutical preparations (preparations need to be sterile/sterilisation). Microbe/pathogen management (use disinfectants/antiseptics). Infections in or on the human body (use antibiotics)

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Describe the sterilisation of microbes (1)

Complete removal of microbes or damaging microbes such that all are killed. Sterilisation of microbes doesn't use antimicrobial agents (critical importance in relation to drug preparation)

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Describe the sterilisation of microbes (2)

Methods - heat (dry/wet), ionising radiation (gamma-irradiation from 60Co source, filter sterilisation). Normally damages microbial cells/viruses (can't use strategies in humans)

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Describe features of normal bacterial growth in the laboratory

Inoculate a sterile clear growth medium with a few cells. Over time bacteria grow and turn the medium cloudy. High cell numbers - 10^10/mL. Graph for all bacterial species (lag phase, log phase, stationary, death phase)

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Is it better to kill the target microbe or prevent it from growing?

Possible to try immune intervention when there is an infection

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Introduction to Infection and Pharmaceutical Microbiology

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