TOPIC 2 INFECTIOUS DSEASE Chapter 2.5 Adaptations of pathogens Understanding Pathogens have adaptations that facilitate their entry into the cells and tissues of hosts. Describe how pathogens and host cells recognise each other. Explain that some pathogens enter cells to survive and reproduce. Describe the basic concept of molecular recognition, e.g. pathogens binding to cellular receptors. Explain that some pathogens must enter cells to ensure their survival replication, and to evade the immune system. SACE 2016 In Chapters 2.1 and 2.2, pathogens that give rise to infectious disease were examined in some detail. To cause disease all pathogens must colonise their specific host, avoid immune systems, multiply and then be able to spread themselves to other hosts. Many pathogens are termed intracellular as they enter cells and it is here that they survive and multiply. The ability to cause disease in a host is called pathogenicity and virulence is the degree to which the pathogen causes disease. A pathogen with high virulence has properties that enable it to bring about a high level of disease in a host. Humans are vulnerable to penetration by pathogens in four main ways: respiratory surfaces wounds digestive system reproductive organs Refer to Figure 251 which illustrates how humans can be vulnerable to pathogen entry. Entry points for pathogens Respiratory surfaces air borne pathogens may enter the mouth and nose and be absorbed across mucous membranes of the respiratory surfaces Wounds the skin generally provides a good proctive barrier to microbes but if skin is broken, as in a cut, then pathogens can enter Digestive system if food is contaminated then pathogens can enter via the mouth and enter the digestive system Reproductive organs urethra in males and females and vagina in females Sexually transmitted pathogens can enter across mucous membranes. Figure 251 How microorganisms can enter the body 106 Essentials Education 2016.
ADAPTATIONS OF PATHOGENS CHAPTER 2.5 Adaptations There are many adaptations processed by pathogens to facilitate their entry, survival and reproduction in hosts. Using a vector Some pathogens manage to enter the bloodstream by using a vector to assist them. A rather large group of microbes, including examples from bacteria, viruses and protists, have adapted to survive in certain insects so they can be transferred to their hosts. The disease of malaria is spread in this way with the Plasmodium organism being well adapted to living in certain species of mosquito. Figure 252 shows a mosquito biting a human. Attachment to host tissue Many pathogens are well adapted, once inside the host, to attach to host cells so that food moving through the intestines or the washing action of urine flow does not expel them from the body. They produce specific proteins called adhesions that can recognise and bind in a complementary manner to molecules on host cells. An assignment is provided at the end of this Chapter to help you understand this. Figure 253 shows surface projections (pili) that have proteins at the tip that can bind to cell receptors. Figure 252 A mosquito biting a human Figure 253 E. coli bacterium showing pili Ability to withstand harsh environments The human stomach provides a particularly harsh environment for pathogens; it contains acid with ph 2, thick mucous layers and continual churning action. Nonetheless, a bacteria, Heliobacter pylori, which can cause stomach ulcers can survive and reproduce. One of its adaptations is its ability to secrete an enzyme which converts urea to ammonia which helps to combat the acidic environment. Biofilms More than 99% of bacteria exist in colonies known as biofilms, adopting a range of unique properties such as existing in a dormant state with reduced metabolism, becoming resistant by transferring genetic information within the colony and preventing antibiotic penetration by surrounding themselves in a slime-like matrix. All of these factors result in biofilm bacteria being difficult to identify using standard culture-based methods and resistant to traditional antibiotic therapy. One particular bacterium, Staph. aureus is known to cause many sinus infections and is very difficult to treat with antibiotics. See Figure 254. Figure 254 Staph areus and a biofilm Essentials Education 2016 107
TOPIC 2 INFECTIOUS DSEASE Producing toxins It is often noticed that microbes may employ more than one specific adaptation to assist in their survival. In the above example of the bacteria H. pylori, they secrete adhesion molecules and also produce toxins that destroy the cells lining the stomach, thereby causing an ulcer. Another bacterium, Bordetella pertussis, which causes whooping cough also produces toxins which destroy cells lining the respiratory tract which reduces the infected person s chance of clearing the infection. Binding to molecules on the surface of host cells Nearly all intracellular pathogens need to bind to receptor molecules on the surface of the host cells. This concept has already been described with the production of adhesion molecules produced by bacteria. Virus particles possess surface molecules that can bind in a complementary manner with surface receptor molecules and this enables them, in many instances to be taken into the cell. Viral infection, including uptake and replication is examined later in this Chapter. Refer to Figure 255. protein RNA lipid bilayer cell receptor Figure 255 A virus binding to cell receptors Figure 256 An example of phagocytosis Ability to survive inside white blood cells Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It is taken into the lungs and from here white blood cells engulf the bacteria. The body s immune system contains the infection within a lesion (tubercule) and it is known that the pathogen can survive inside the white cells inside the lesion for decades. The bacteria that causes Legionnaires disease has a similar adaptation. Figure 256 shows a white blood cell engulfing a bacterium by phagocytosis. Altering the behaviour of the host organism Pathogens may alter the behaviour of their host which may assist in the spread of the microbe to other hosts. Two examples of this type of action are: Inducing diarrhoea; whilst this may flush some bacteria from the gut assisting the host, it also enables infections to spread via contaminated water. (e.g. cholera) Coughing and sneezing with colds or influenza will expel virus particles in tiny droplets which may then be inhaled by others to cause the spread of the disease. It has been estimated that in one sneeze there may be up to 20,000 droplets and if the person is infected with rhinovirus this may be thousands of viral particles. Changing antigens on the surface of the microbe Antigens on the surface of pathogens are the molecules that are recognised by the host organism and represent a critical phase in the recognition and destruction of the invading organism. One powerful adaptation of many bacteria and viruses is their ability to change their outer antigen configuration to help evade the human s immune system. This concept will be discussed further in coming chapters. 108 Essentials Education 2016.
ADAPTATIONS OF PATHOGENS CHAPTER 2.5 Drug resistance Chapter 2.3 examined the ability of bacteria to develop resistance to antibiotics, with this looming as one of the most significant threats to human health in the coming decades. Superbugs is a term coined to describe the new strains of bacteria that are resistant to all known antibiotics. Avoiding white blood cells (phagocytes) Figure 256 illustrated a white blood cell, called a phagocyte, engulfing a bacterium with the aim of destroying it. Most bacteria that are successful as pathogens have evolved ways to avoid being engulfed by these white blood cells. Viral replication Virus particles are not cellular, they do not display many properties of other microbes but they can enter a host cell and use the host s DNA and ribosomes to make new viral particles that can leave the cell and infect other cells in either the same or other hosts. As such, viruses lack the necessary organelles such as ribosomes to make protein molecules. Viruses are specific in the cells they infect, this is determined by the complementary binding between their surface antigens and host receptor molecules. Refer again to figure 255. Refer to Figure 257 which illustrates the five general steps of the viral reproductive cycle. In the process of transcription, DNA is used to make a molecule of mrna (messenger RNA). mrna can be used to make viral protein molecules on organelles called ribosomes, this is called translation. Copies of viral DNA can be replicated to make more copies, using host cell chemicals and energy. Attachment of the virus to complementary surface receptor molecules on the cells surface 1 Virion 2 Virus moves into the cell by endocytosis Cytoplasm Replication of viral DNA using host DNA 3 Transcription 5 Package and assembling of new virus particles Translation Synthesis of new viral components using host cell ribosomes 4 Figure 257 The five general steps of the viral reproductive cycle Helpful Online RESOURCES about viral replication Use this QR code to jump to our website which will provide an EVA about viral reproduction: <http://essentialseducation.com.au/resources/sace-1/biology/viral-replication/> Essentials Education 2016 109
TOPIC 2 INFECTIOUS DSEASE Human Endeavour EXERCISE 2.5 - The HIV/AIDS drug AZT The drug AZT has been used since about 1987 in the treatment of HIV infection. Do some research and write concise answers to the following questions. 1. Explain how the drug works to reduce the symptoms of the disease. 2. State reasons why the drug is not 100% successful in eliminating the virus. 3. Describe and state reasons for a complication or side effect of using the drug. 4. Explain one way in which HIV can change to develop resistance to the drug Use your own paper or a screen as directed by your teacher. Helpful Online RESOURCES about AZT Use this QR code to jump to the website below which will provide a valuable start in your research for this Assignment: <http://www.britannica.com/science/azt> Plant pathogens Organisms that can bring about plant disease are again many and varied and include pathogens such as fungi, bacteria, viruses and viroids and nematodes. Fungi Fungal pathogens can infect plant tissue and obtain nutrients from the plants cells. Figure 258 (a) shows Tomato Blight a fungal infection of tomato leaves. Phytophthora root rot is caused by the soil fungus Phytophthora cinnamomi. This disease can affect native plants and is a major threat to some rare and endangered species. The fungus often grows through the root system and in the process destroys the plant s ability to absorb water and nutrients. The fungus produces spores which can survive for long periods of time in the soil. The disease has spread over most of Australia and has been very difficult to diagnose and treat. Methods of reducing the impact of Phytophthora include: quarantine-fencing off infected populations and reducing public access hygiene practices-e.g. sanitising tools and boots (see Figure 259 overpage) spraying infected plants Figure 258 (b) illustrates dieback caused by Phytophthora. Figure 258 (a) Tomato blight Figure 258 (b) Phytophthera dieback 110 Essentials Education 2016.
ADAPTATIONS OF PATHOGENS CHAPTER 2.5 Figure 259 (a) and (b) A boot cleaning station in a National Park in Queensland Figure 2510 Bacterial infection Figure 2511 A nematode Bacteria There are about 100 known species of disease-causing bacteria in plants. They bring about their pathogenicity by producing toxins or other proteins that cause disease. Pseudomonas syringae causes tomato plants to yield less crop and has several adaptations to facilitate its spread including the production of chemicals that help evade the tomato plants immune system. Figure 2510 shows an example of this bacterial infection. Viruses and viroids Viroids are smaller than virus particles and contain RNA. An example of one of the first of these to be discovered was the potato spindle tuba viroids. Often plant viruses and viroids can be transmitted by a vector. Nematodes Nematodes are small, wormlike creatures that have the capacity to cause significant damage to root cells in plants. There are a number which infect food crops e.g. potatoes, cucumbers and strawberries. Figure 2511 illustrates a soil nematode. Key Concepts 1. For pathogens to cause disease they need to: colonise the host avoid the immune system reproduce spread to other hosts 2. Different pathogens or members of related species have different levels of virulence. 3. Entry into human hosts is usually through: wounds respiratory surfaces reproductive organs digestive system 4. Pathogens have evolved a vast range of adaptations that enable them to survive and spread including hiding inside cells. 5. Viruses use the host cells enzymes, nucleic acids and organelles to produce new viral particles. 6. Plants are also highly susceptible to pathogens which cause major problems to the agricultural industry. Essentials Education 2016 111
TOPIC 2 INFECTIOUS DSEASE What have you learned? Key terms immune system adaptations complementary binding receptor molecules pili toxin intracellular transcription translation phagocyte rhinovirus antigen ribosomes pathogenicity virulence viroids nematodes Knowledge and Understanding 1. Name three ways that pathogens enter the human body and give an example of a pathogen for each. 2. State the difference between pathogenicity and virulence. 112 Essentials Education 2016.
ADAPTATIONS OF PATHOGENS CHAPTER 2.5 3. Pathogens have a range of adaptations to assist them in entering, reproducing and exiting hosts. Complete the following table regarding the type of adaptation, how it provides an advantage and an example of a pathogen that possesses such an adaptation. Adaptation Using a vector Production of toxins Hiding inside host cells Description of how the adaptation works Attachment to host cells to avoid being flushed out of host Example Helicobacter pylori 4. Describe how fungal spores provide a reproductive and/or survival advantage to those species that produce them. Application, Analysis and Evaluation 5. Compare two pathogens; one with high virulence and one with low virulence. Explain the features that contribute to the virulence. 6. High virulence can be seen as a disadvantage to the pathogen. Explain the reasons for this. 7. Compare and contrast two methods for controlling the spread of the plant fungus Phytophthera. 8. Causing diarrhoea can be seen as an advantage for both the host and pathogen. Argue how this is possible. 9. Show how a pathogen gains an advantage by hiding inside a host cell. Essentials Education 2016 113
TOPIC 2 INFECTIOUS DSEASE Extension 10. Select a pathogen which infects a plant of direct commercial value such as a plant that is used for food or fibre. Do some research on this topic to answer the following questions. a) How is this pathogen transmitted to the plant? b) What are the symptoms displayed by the plant when infected? c) What is the commercial impact of this disease on the crop that is produced? d) What treatment and/or management plan is used in order to try to minimise the effect of this disease? Present your report according to the guidelines given by your teacher. Helpful Online RESOURCES for plant diseases Use this QR code to jump to the website below which will provide a valuable start in your research about plant diseases: <https://en.wikipedia.org/wiki/category:plant_pathogens_and_disease> Human Endeavour ASSIGNMENT 2.5 The profile of a real scientist Carefully read the profile of Dr. Donald Gardiner, a plant pathology scientist, who grew up and went to school in Adelaide and now works with the CSIRO in Brisbane. See next page. Discuss how his work (and his colleagues in other laboratories) exemplifies the following aspects of Science as a Human Endeavour. You may wish to consult the SACE syllabus statement for more detail about each of the headings below. You may need to do some research into CSIRO and other large research organisations. Your teacher will provide more information about the details of your report. 1. Communication and collaboration a) Science is a global enterprise b) International collaboration 2. Development a) Development of complex scientific models and/or theories b) New technologies 3. Influence a) Advances in one field can influence other areas of science b) The use of scientific knowledge can be influenced by other considerations 4. Application and limitation a) Scientific knowledge can be very widely used b) The use of scientific knowledge may have beneficial or unexpected consequences c) Science informs public debate and is in turn influenced by public debate Helpful Online RESOURCES for CSIRO Use this QR code to jump to the website below which will take you to CSIRO and provide a valuable start in your research for this Human Endeavour Assignment: <http://www.csiro.au/en/research/af> 114 Essentials Education 2016.
ADAPTATIONS OF PATHOGENS CHAPTER 2.5 PROFILE for Human Endeavour ASSIGNMENT 2.5 Dr. Donald Gardiner My work aims to understand how a group of the most devastating fungal pathogens of wheat invades their host plant. The pathogens are called Fusarium graminearum and its close relative, Fusarium pseudograminearum. During infection they produce a toxin, called deoxynivalenol, which both assists with invasion of the plant and also contaminates any grain that is harvested from the crop. This toxin is highly harmful to humans and animals that may eat the grain. By understanding the mechanisms a pathogen uses to cause disease, we hope to be able to implement better control strategies that will assist the farmer to protect their crops and deliver safer food to consumers. In modern molecular biology, having a genome sequence for your organism of interest is highly advantageous. With new DNA sequencing technology, obtaining genomes for fungi is relatively straight forward. However, the way the genome sequence is obtained means it remains in literally millions of pieces that need to be put back together and this can be a challenging task. With advanced software and high performance computing, we can now put most of these pieces back together. For our Fusarium species,when this is done we typically end up with genomes in about 500 pieces. Each of these pieces will contain hundreds of different genes. By predicting the genes that are encoded by the genomes we can begin to understand how the pathogen has evolved and the mechanisms that it uses to invade its host. This is done by comparing all of the genes encoded by a pathogens genome with those of both closely and distantly related organisms. The general term for approaches like this is comparative genomics. One of the most fundamental components of comparative genomics is the ability to compare the sequence of the genes or proteins encoded by an organism s genome. One tool that is extensively used is BLAST; (basic local alignment search tool). I have previously used BLAST to compare the entire gene set of many different genomes of fungi all at once. These comparisons can be used to identify highly conserved genes, that might be important for basic cellular functions such as energy generation or DNA replication, and genes that are less well conserved or only present in a few species. It is this latter group that might contain genes involved in virulence on a particular plant host. Using this approach we recently discovered genes in the genome of Fusarium pseudograminearum that had been horizontally transferred between distantly related fungi that all shared a common plant host (Gardiner, McDonald et al. 2012). In some example genes were also shown to be transferred between bacteria and fungi. To test the hypothesis that these genes (shared exclusively between pathogens with a common host) are involved in virulence, mutant strains of the fungus are created and compared to the wild type strain in plant infection assays. This is done by replacement of the gene with an antibiotic resistance gene using homologous recombination. This creates a mutant organism that, apart from the deleted gene and antibiotic resistance is identical to the original pathogen. These strains are then compared for their ability to infect the host plant in a controlled environment room. Through this process we can begin to understand how these fungi cause disease on wheat. Education and career I studied a Bachelor of Biotechnology (honours) at the Flinders University of South Australia and completed a PhD in molecular plant pathology at Melbourne University where I researched the interaction between canola and a fungal pathogen. After a brief post doctoral fellow at the University of Queensland, undertaking research in mammalian genomics, I joined the Australian Commonwealth Scientific and Industrial Research Organisation in 2005, where I have been researching Fusarium incited diseases of a number of crop plants ever since. Gardiner, D. M., M. C. McDonald, et al. (2012). Comparative pathogenomics reveals horizontally acquired novel virulence genes in fungi infecting cereal hosts. PLoS Pathog 8(9): e1002952. Essentials Education 2016 115