Lecture 1.2 -Introduction to microbes and infection PDF

Difference between prokaryotic and eukaryotic cells: Commensal organisms (Microbiota): ◦Commensals live on the surface of our bodies and in specific areas e.g. intestinal tract, oral cavity, vagina ◦Includes bacteria and fungi ◦Known as microbiome ‣ Staphylococcus aureu...

Difference between prokaryotic and eukaryotic cells: Commensal organisms (Microbiota): ◦Commensals live on the surface of our bodies and in specific areas e.g. intestinal tract, oral cavity, vagina ◦Includes bacteria and fungi ◦Known as microbiome ‣ Staphylococcus aureus and staphylococcus epidermidis - skin ‣ Streptococcus mitis - upper respiratory tract ‣ Candida albicans (yeast) - oral, gastrointestinal and vaginal mucosa ‣ Lactobacillus species - vagina ‣ Species of bacteroides - gut Naming of bacteria, fungi and Protozoa: ◦Genus + species (“surname + first name”) for example: Staphylococcus aureus (Staph aureus, S.aureus) ◦Names are sometimes supplemented by adjectives describing growth, typing or antimicrobial susceptibility characteristics, for example E. coli 0157, MRSA (methicillin resistant staph aureus) ◦Names are subject to change ‣ For example Clostridium difficile is now known as Clostridioides difficile) Structure of bacteria: Oxygen tolerance: ◦Aerobes - can survive in the presence of oxygen ◦Obligate aerobes - require oxygen for survival ◦Anaerobes - can survive in the absence of oxygen ◦Obligate anaerobes - require oxygen-free environment for survival (unless able to form spores) Properties of bacteria: ◦Most can be grown on liquid or solid medium containing relevant nutrients. Some exceptions e.g. Rickettsia and Chlamydia are intracellular  bacteria. ◦Most have a cell wall with peptidogylcan ‣ Exception is Mycoplasma species which do not have a cell wall but have a plasma membrane consisting of a lipid bilayer ◦Staining (gram stain, acid fast stain, India ink) ◦Morphology ◦Fermentation, oxidation, enzymes Gram positive and gram negative bacteria: Bacterial shapes: Arrangement of cocci: Mechanisms of bacterial pathogenesis: ◦Virulence factors: ‣ Evasion of immune system (e.g. polysaccharide capsule) ‣ Adherence to host cells (e.g. pili and fimbriae) ‣ Invasiveness (e.g. enzymes such as collagenase)  ‣ Toxins: Exotoxins (e.g. dipheria toxin) - toxins released to the environment Endotoxins (lipopolysaccharide) - part of the bacteria itself Enterotoxins - released in the gut by bacteria and cause things like gastroenteritis Endospores: ◦Some bacteria develop endospores to survive lack of nutrients or other adverse environmental factors ◦The genetic material is preserved ◦Highly resistant form which can withstand chemicals and extremes of temperature ◦Examples are Clostridium difficile (Clostridioides difficile), Bacillus cereus Some medically important bacteria: Group A Streptococcus (GAS): ◦Group A Streptococcus is a commensal which can be present in the throat and on the skin of normal individuals ◦Normally group A streptococcus (streptococcus pyogenes) causes mild illnesses e.g. tonsillitis, pharyngitis, impetigo, cellulitis and scarlet fever. ◦May be due to increase in circulating viruses and GAS causing secondary infection Treatment of bacterial infections: ◦Antibiotics interfere with: ‣ Cell wall synthesis ‣ Protein synthesis ‣ Nucleic acid synthesis ‣ Cell membrane function Viruses: ◦Intracellular obligate parasites ◦Genetic material is RNA or DNA ◦Enveloped or non-enveloped ◦Capsid symmetry can be helical or icosahedral which gives viruses their shape  ◦Envelope: lipid bilayer membrane (e.g. plasma membrane, internal cell membranes such as the nuclear membrane, endoplasmic reticulum, Golgi apparatus) acquired as the virus buds through the host cell cytoplasmic membrane ◦Capsid: protein coat for viral genome and proteins Properties of envelopes and non-envelopes viruses: ◦The envelope viruses are more sensitive to harsh environments, for example, heat, dryness, compared to non-enveloped viruses ‣ These are generally transmitted by respiratory, parenteral and sexual routes ◦The non-enveloped viruses are more stable in adverse environments ‣ These are generally transmitted by the faecal-oral route DNA viruses: RNA viruses: Coronaviruses (CoV): ◦Enveloped ◦Positive sense ◦Single stranded RNA ◦They infect humans, other mammals and avian species  Monkey pox virus: ◦Same family as variola virus (small pox) not related to chicken pox (VZV) ◦Same symptoms as small pox but milder and not fatal ◦Spread - direct contact with monkey pox rash and scabs from a person with monkey pox, as well as contact with their saliva, upper respiratory secretions and areas around the anus, rectum or vagina ◦Detected by taking swab from lesions and PCR ◦2 vaccines - prevention - not in general use Virus growth: ◦Need living cells to replicate (obligate intracellular parasites) ◦Use the living cells to synthesise all the constituents of the virus ◦Different viruses grow in different types of cells ◦In the laboratory: ‣ Vero cells ‣ HeLa cells ‣ Baby hamster kidney cells (BHK) Steps in viral replication: ◦Viruses undergo similar sequence of events: ‣ Attachment to the appropriate cells (e.g. haemagglutinin of influenza virus or glycoprotein GP 120 of HIV to appropriate cell receptor) ‣ Penetration of virus into cell (endocytosis or fusion of envelope with host cell membrane) ‣ Unloading viral capsid is removed by viral enzymes or host enzymes leading to release of their genome and other materials such as enzymes into the host cell ‣ Replication - initiation of transcription or translation of the viral genome resulting in the manufacture of virus components and genome ‣ Assembly of components into new visions which are ready for the release ‣ Release of the visions by lysis or budding from the target cells and further infection. DNA virus replication: ◦Transcription and replication occurs in the nucleus of the infected cells ◦Most DNA viruses assemble in the nucleus ‣ Early transcription (translation of proteins for DNA replication) ‣ Late transcription (translation of structural proteins) ◦Assembly and release RNA virus replication: ◦RNA viruses normally undergo transcription, translation and replication in the cytoplasm. ‣ Positive sense single stranded RNA can function as mRNA and get translated into proteins by the host ribosomes ‣ Negative sense RNA has to be changed to positive mRNA using the enzyme RNA dependent RNA polymerase to make a positive strand copy, which can be read by the ribosomes and result in the manufacture of proteins. Latency: ◦Latent viral infection - the virus can remain dormant within cells and does not cause symptoms until it is activated by some factors. ◦Immunosuppression (chemotherapy or infections such as HIV result in reactivation of latent viruses) ◦Examples of latent viruses are:  ‣ Herpes simplex viruses ‣ Varicella zoster virus (chickenpox and reactivation causes shingles) ‣ Cytomegalovirus ‣ Epstein Barr virus (EBV) Bacteriophages: Overview of viral infections: Antivirals: ◦Inhibits viral DNA ‣ Acyclovir Herpes simplex - genital herpes, encephalitis Varicella zoster - chicken pox and shingles ◦Inhibits viral neuraminidase (required in release of virus from the cell) ‣ Tamiflu Influence A and B ◦Specialist agents for HIV, HBV, HCV, CMV Fungi: ◦Saprophytic or parasitic eukaryotes ◦Produce spores ◦Cell wall (chitin) and cell membrane (ergosterol) different from bacteria and other eukaryotic cells ◦Thus antifungals target different entities and processes to antibiotics ◦For example, Amphotericin B and nystatin bind to ergosterol, form pores and result in cell death. Examples of fungi: ◦Yeast (single-celled) ‣ Candida albicans (thrush) ‣ Cryptococcus neoformans (usually affects the lungs or the CNS) ‣ Pneumocystis jiroveci (pneumonia)  ◦Molds - a type of fungus (multicellular) ‣ Aspergillus species (lungs) ‣ Dermatophytes (also called ringworm as causes itchy, red, circular rash). Examples are tinea pedis (athletes foot) and tinea capitis (when in the scalp) Antifungals: ◦Azoles (active against yeasts +/- molds) ‣ Inhibit cell membrane synthesis Fluconazole used to treat Candida ◦Polyenes (nystatin and amphotericin) ‣ Inhibits cell membrane function Nystatin for topical treatment of candida Amphotericin for IV treatment of systemic fungal infections (e.g. aspergillus) ◦EMERGENCE OF RESISTANCE Protozoa: ◦Protozoa- unicellular eukaryotic organism ‣ Giardia lamblia - parasitic intestinal disease ‣ Cryptosporidium parvum - intracellular parasite - epithelial cells of the villi in lower small intestine ‣ Plasmodium falciparum - malaria ‣ Trypanosoma brucei - sleeping sickness Helminths: ◦Helminths (worms, multi-cellular) divided into three groups: ‣ Cestodes: ribbon-like, segmented intestinal parasites - Tapeworms (e.g. Taenia saginata - beef tapeworm) ‣ Nematodes: long non-segmented worms - roundworms (e.g. Enterobius vermiculite’s - pinworm) ‣ Trematodes: small, flat leaf-like worms that can infect urinary bladder, liver, lungs, blood vessels in the intestine - Flukes (e.g. Schistosoma mansoni - blood fluke) Guinea worms: Prions: ◦Unconventional infectious agents ◦Prions are infective proteins with no nucleic acid ◦Causative agent of transmissible Spongiform Encephalopathies ◦Accumulation of prion protein in the grey matter and in extracellular amyloid plaques in the brain ‣ Scrapie in sheep  ‣ Bovine Spongiform Encephalopathy (BSE) in cattle ‣ Creutzfeldt-Jakob disease (CJD) Human papilloma virus and cervical cancer: ◦Human papilloma virus - non enveloped DNA virus Epstein Barr virus (EBV): ◦EBV is a double stranded DNA enveloped virus ‣ Also known as human herpes virus 4 (HHV 4) ‣ Infection results in sore throat, fever, swollen glands (lymphadenopathy) ‣ Glandular fever (infectious mononucleosis) ◦EBV is linked to a number of cancers including: ‣ Burkitt lymphoma ‣ Nasopharyngeal cancer ‣ Stomach cancer