Block 1, Microbes PDF

Okay, here are detailed lecture notes based on the provided sources, covering the various topics presented in the first block of lectures. Animal Pathogens 1 Aims: The lecture aims to describe a range of animal pathogens, explain their strategies to avoid host defenses, consider anim...

Okay, here are detailed lecture notes based on the provided sources, covering the various topics presented in the first block of lectures. Animal Pathogens 1 Aims: The lecture aims to describe a range of animal pathogens, explain their strategies to avoid host defenses, consider animal husbandry, and describe the consequences and control methods. What are Animal Pathogens? Infectious agents that cause disease in animals and humans. Where are they? Everywhere! Why do we care? They impact human welfare and have a significant economic impact. The concept of "One Health" is relevant. o Billions of pounds are lost each year due to animal pathogens. o They pose health risks, including fatalities, foodborne illnesses, poor development, and endemic diseases. o Economic risks include the need for diagnostics and vaccines, market disruptions, and productivity losses. Economic Impact Example: The 2001 UK Foot & Mouth Disease outbreak resulted in approximately 2,000 cases, 6 million culled animals, and an estimated £8 billion loss. It also led to changes in food security practices. Four Diseases of Cattle Discussed: o Bovine tuberculosis (bacteria) o Trypanosomiasis (Nagana) (parasite) o Ringworm (fungi) o Rinderpest (virus) Bovine Tuberculosis: o Caused by Mycobacterium bovis, part of the M. tuberculosis complex. o Infects cattle and other mammals, with 100 types, 14 are cancer-causing. HPV types 16 and 18 cause 70% of cervical cancers. Cervical cancer had 530,000 new cases in 2012, with 84% in less developed regions. High risk HPV is also associated with anus, vulva, vagina and penis cancers. o HPV Screening: Involves a molecular test for high-risk HPVs. If HPV is detected, abnormal cells are checked microscopically (cytology). If abnormal cells are detected, the patient is referred for colposcopy. HPV molecular testing as primary screen introduced in Scotland in 2020. o HPV Vaccination: HPV 16 and 18 cause 70% of cervical cancers. HPV 6 and 11 cause genital warts. Gardasil 9 protects against types 6, 11, 16,  18, 31, 33, 45, 52, and 58 (~90% of HPV types causing cervical, vulvar, vaginal, and anal cancers). Retroviruses and Cancer: o Mechanisms: Transducing (animal only), cis-activating (animal only), and trans-activating (human). o Transducing Retroviruses: Carry oncogenes which lead to the formation of tumours. o Cis-acting Retroviruses: Viral insertional mutagenesis can activate cellular oncogenes. o Trans-Acting Retroviruses: e.g. HTLV-1. Tax is a transcriptional activator of LTR. HIV-1: Not cancer inducing, but suppresses the immune system leading to increased risk from normal cancers. Cancer and Hepatitis: o Hepatitis B virus (HBV) and hepatitis C virus (HCV) chronic infections are a leading cause of hepatocellular carcinoma (~70% of cases). o Hepatitis B Virus (HBV): A DNA virus that attacks the liver, causing acute and chronic disease. Chronic infections can lead to cirrhosis and/or liver cancer. o Hepatitis C Virus (HCV): A cytoplasmic RNA virus that can cause acute and chronic hepatitis. 20-40% clear the virus, while the rest develop chronic HCV with risk of cirrhosis. o How they cause hepatocellular carcinoma: This is due to molecular mechanisms induced by the viral infection. o HBV Vaccine and Treatment: WHO is encouraging increased vaccination, which is now part of the UK childhood schedule. HBV antiviral drugs are available (long-term therapy), but they reduce, not eliminate the risk of HCC. o Curing HCV: Virus targeting drugs are highly effective. WHO aims for an 80% reduction in infection by 2030. Cures chronic infection in >90% of cases with treatment lasting 8-12 weeks. The biggest impact on HCC risk is predicted in patients treated before cirrhosis has developed, but treatment is expensive.  Summary: Viruses are associated with ~13-15% of cancers worldwide. Viruses associated with cancer include: retroviruses (HTLV-1), herpesviruses (EBV, KSHV), papillomaviruses (14 high risk HPVs), and hepatitis viruses (HBV and HCV). Cancer can be caused directly (e.g. HPV) and indirectly (e.g. hepatitis viruses). Vaccines for HPV and HBV can prevent associated cancers. Plant Pathogens Aims: The lecture aims to understand the importance of plants and the impact of plant pathogens, describe specific plant pathogens and strategies to control them, and discuss the challenges faced by plant pathogens, and how plant pathogens can be exploited. Importance of Plants: Vital for atmospheric oxygen, food, environment/wildlife, and carbon storage. Also useful for textiles, biofuels, medicines and vaccines. Impact of Plant Pathogens: Many different pathogens exist. Plant pathogens cost the global economy an estimated US$220 billion per year and cause 20- 40% crop losses. They threaten food security, livelihoods and plant species, and climate change is likely to increase the spread and change the distribution of plant pathogens and pests. Plant Pathologies: o Necrosis: death of cells o Soft rot: enzymatic degradation of plant tissues o Wilt: loss of turgor in leaves o Blight: discolouration, wilting and death of foliage o Cankers: dead sections of bark o Gall: tumourous growth Potato (and tomato) late blight: o Mass starvation in Europe in the 1840s due to successive epidemics of potato late blight, caused by Phytophthora infestans. o Up to 1 million people died, and 2 million emigrated during the Irish Potato Famine (1845-1855). o Devastating plant disease even today, causing $6.7 billion losses annually. o Caused by the oomycete Phytophthora infestans, which synthesises cellulose cell walls.  o Dispersed by sporangia which release motile zoospores. o Control: Highly challenging as P. infestans rapidly adapts to control measures. Intensive use of fungicides, destroying foliage, and breeding resistant cultivars are used as control methods. CRISPR/Cas9 technology may help. Fusarium wilt of banana: o Bananas are the most traded fruit, with >400 million people relying on them. o Fusarium oxysporum fungus causes banana wilt (or Panama disease). o The Gros Michel banana variety was susceptible to F. oxysporum Tropical Race 1 (TR1), which was replaced with the Cavendish variety. The Cavendish variety is now threatened by TR4 Fusarium. o Control: Hard to eradicate as it persists in the soil and infects via the roots. Commercial monoculture means there are few options for resistant strains. Prior exposure to an avirulent TR1 strain can offer temporary protection. Multi-site fungicides are also being developed. Dutch Elm Disease: o Caused by the fungi Ophiostoma ulmi and O. novo-ulmi, discovered in Holland in 1921. o Spread by the elm bark beetle, root grafts, and infected logs. o The fungus blocks water conduction channels (xylem), causing wilt, with host defence responses also plugging the vessels. o Shoots die back from the tip. o First appeared in NW Europe in 1910 (O. ulmi), with a second outbreak in late 1960s caused by the highly aggressive O. novo-ulmi. o Introduced into England from Canada in the 1960s killing the majority of mature elms. o Control: Early reporting and action, reducing the elm bark beetle population, preventing root grafting, and using fungicides are used for control. Ash Dieback Disease: o Caused by the wind-borne fungal pathogen Hymenoscyphus fraxineus, first detected in the UK in 2012.  Challenges for Phytopathogens: o Plants vary greatly in temperature. o Basic transport/communication system that hinders transport of microbes. o Surface microbes are exposed to oxygen, organic matter, light and UV irradiation. o Root microbes have less variable environment and high nutrient levels. o Vulnerable to extremes of weather. o Getting in: Waxy coatings on leaves and stems, so bacteria enter through gas or water pores or wounds, nematodes use stylets, and fungi use hyphae and haustoria. Plant Immune Response: o PAMP-triggered immunity (PTI): A general immune response against many pathogens which is fairly weak. o Effector-triggered immunity (ETI): A stronger immune response to specific pathogens that can lead to systemic acquired resistance (SAR). Plants also have in-built tolerance to some microbes. All cells are capable of mounting an immune response. o 1. PAMP-Triggered Immunity: PAMPs are recognised by plant pattern recognition receptors (PRRs). This results in defensive molecules to impede the pathogen. Some pathogens produce avirulence (Avr) effector proteins to avoid PTI. o 2. Effector-Triggered Immunity: Plant resistance (R) protein receptors recognise pathogen effector molecules. Plant resistance proteins can also trigger ETI by sensing damaged plant molecules (DAMPs). ETI triggers Ca2+ signalling, reactive oxygen species (ROS), accumulation of pathogenesis-related proteins, and hypersensitive response. Changes in plant hormone levels may lead to SAR. Results of Pathogen Detection: Cell wall modification, closure of stomata, production of ROS, hypersensitive response, and production of anti-parasite compounds and proteins. Management of Plant Pathogens: Avoidance, therapy, eradication, breeding resistant/genetically modified plants, and biocontrol. Exploitation of Plant Pathogens:  o Pseudomonas spp.: Can be human and plant pathogen, a nosocomial pathogen, a bioremediation agent, a biocontrol agent, and causes disease in a wide range of crops. Some also form biofilms and have intrinsic antibiotic resistance. o Tobacco mosaic virus (TMV): The first virus discovered, easily purified RNA virus. It encodes 2 replicases, movement protein and a coat protein. Coat protein is replaced by gene of interest to express transproteins. Can form viral nanoparticles. Transgenic plants expressing TMV components display resistance to TMV and related plant viruses. o Agrobacterium tumefaciens: A bacterium causing crown gall disease. The Ti plasmid can be disarmed and used to insert recombinant proteins into plants. It can also be used for disease resistant plants and production of pharmaceuticals. Summary: Plants are vital for life, and plant pathogens can be devastating for the environment and food security. Control of plant pathogens is challenging. Plant immune response comprises weak PTI and strong ETI arms. Plant pathogens can be exploited for industrial, agricultural, medical, and biotech applications. The Global Impact of Microbes Aims: The lecture aims to understand the global ecological impact of microbial life, how microbes have helped shape the planet, methods of identifying and grouping organisms, and the differences between bacteria and archaea. Ecological Impact of Microbes: Knowledge of global microbiology is limited, with only 0.1% of microbes in the biosphere culturable in the lab. Robert Koch identified specific organisms’ relation to disease, reliant on isolating pure cultures. Angelina and Walter Hesse used agar as growth media. Capacity to Culture: Sergei Winogradsky identified bacteria that could fix carbon dioxide using inorganic minerals (lithotrophs). He developed the ‘Winogradsky column’ model wetland. Bacteria and Nitrogen Cycling: Cycling of nitrogen is dependent on bacteria, and the availability of nitrates (NO3) is the rate-determining step in plant growth. Intensive farming has caused an imbalance in nitrogen recycling, with NO3 artificially generated. Symbiotic Relationships: o Interconnected relationships: with insects, plants, and animals. o The ‘Hoff’ (Kiwa tyleri): A crab that eats bacteria it farms on its hairs.  o Leaf cutter ants: Cultivate bacteria on their bodies that produce metabolites with anti-microbial properties. o Mycorrhizae: Fungal network linking roots that provides a distribution network for nutrients. o Rhizobium: Bacteria that fix nitrogen. Different Biological Entities Studied: Acellular (viruses, viroids, prions) and cellular (fungi, protists, bacteria, archaea). Classical Grouping of Bacteria: Grouped according to shape, size and activity. Molecular Characterization: Small subunit ribosomal 16S/18S sequence analysis used to classify organisms. Carl Woese used the gene for the ribosomal 16S/18S protein as a molecular clock. Consequence of Molecular Evaluation: Evolutionary point of view resolved into 3 kingdoms of life. Archaea: The domain in the middle between bacteria and eukarya. o Common Traits Between Bacteria and Archaea: Size, circular DNA chromosome, DNA organisation (nucleoid), simple cell structure, are all prokaryotes (no nuclear membrane). o Common Traits Between Archaea and Eukarya: Introns between genes, RNA polymerase and transcription factors, and translation initiator (methionine). o Unique Features of Archaea: Methanogenesis, non-pathogenic, and thermophilic growth. Archaea – Extremophiles: Most ecologically diverse colonisers that inhabit a range of extreme environments. They include thermophiles and barophiles, marine organisms, psychrophiles, halobacteria, and methanogens. Not all archaea prefer extreme environments. Methanogens make methane in the gut. The Earth Microbiome Project: Seeks to understand patterns in microbial ecology across biomes. Nomenclature: Hierarchical structure from Domain to Species. Summary: Gained an appreciation of the diversity of microorganisms in the environment and their contribution to global ecology. Molecular tools are used to help curate these organisms. Highlighted the differences between bacteria and archaea. Carbon Recycling Challenges: Climate change, food security and sustainability. Microbes play a role in both the problems and solutions. Aims: To understand microbes contribution to global carbon recycling, their influence on climate change and their positive roles such as detoxification