Lecture 2: Normal Flora & Host-Parasite Relationship PDF

LECTURE 2 NORMAL FLORA & HOST-PARASITE RELATIONSHIP SBGA_020424 Mar-Aug24  Host/microbe interaction Mechanism pathogenicity, virulence and toxigenicity. Normal flora and opportunistic microorganisms of human body. Routes of transmission. ...

LECTURE 2 NORMAL FLORA & HOST-PARASITE RELATIONSHIP SBGA_020424 Mar-Aug24  Host/microbe interaction Mechanism pathogenicity, virulence and toxigenicity. Normal flora and opportunistic microorganisms of human body. Routes of transmission.  What is microbe? What counts as a microbe? Microscopic organism (microorganism) – too small to be seen with the naked eye, especially one that causes disease. *Bacteria *Fungi Archaea Protist *Viruses *Parasites (Toxoplasma, Plasmodium, Babesia etc.) Microbes and diseases (*pathogen).  e.g. Bacteria – TB, cholera, typhoid Fungi – Ringworm, histoplasmosis, candidiasis Viruses – cold, dengue, Covid-19 Parasites – malaria, Chagas disease, toxoplasmosis, amebiasis Exercise: List example of various types of disease-causing pathogens https://www.acko.com/health-insurance/diseases/diseases-caused-by- microorganisms/  Definition Pathogen - an organism causing disease to its host, with the severity of the disease symptoms referred to as *virulence. Pathogenicity - the ability of an organism to cause disease (i.e., harm the host). This ability represents a genetic component of the pathogen and the overt damage done to the host is a property of the host-pathogen interactions. Commensals and opportunistic pathogens lack this inherent ability to cause disease. Pathogenesis - the mechanisms by which it develops, progresses, and either persists or is resolved. Pathology – study and diagnosis of disease. Clinical pathology involves the examination of surgically removed organs, tissues (biopsy samples), bodily fluids, and in some cases the whole body (autopsy). Chemical pathology (also known as clinical biochemistry) involves the biochemical investigation of bodily fluids such as blood, urine and cerebrospinal fluid. Chemical pathology I (CSI212) Chemical pathology II (CSI262)  Definition (short words 😁) Patho - Relating to disease Pathogen - agents (microorganisms) able to cause disease Pathogenesis - development of a disease Pathology - study of disease Pathogenicity - ability to infect a host and cause disease and depends on a number of factors: ability of pathogen to invade a host ability of pathogen to multiply in the host ability of pathogen to avoid host defences (evasion of host immune response (IR)) the number of infectious organisms that enter the body Degree of pathogenicity is called VIRULENCE, with highly virulent pathogens being more likely to cause disease in a host (pathogens varying in their ability) https://microbenotes.com/factors-affecting-bacterial-pathogenicity/  invade D39 evasion of host IR D39 Pathogenicity factors D39 CAMφ SBGA© Activated state multiply bacteria MΦ  Definition *Virulence - a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism - its ability to cause disease which determined by its virulence factors. Virulence factor (VF) - the molecules that assist the bacterium colonize the host at the cellular level. Virulence factor (VF)  Virulence Factor (VF) characteristics that contribute to virulence are called virulence factors (VF): physical structures that the bacterium has (pili, flagellum etc.). chemical substances that the bacterium can produce (toxins). the genes that code for virulence factors are commonly found clustered on the pathogen’s chromosome or plasmid DNA, called pathogenicity islands (PI). PI facilitate the sharing of virulence factors between bacteria due to horizontal gene transfer (HGT), leading to the development of new pathogens over time. Often the genes for virulence factors are controlled by quorum sensing (QS), to ensure gene activation when the pathogen population is at an optimal density. Triggering the genes too soon could alert the host’s immune system to the invader, cutting short the bacterial infection.  Transformation is the uptake of 'free' DNA from the environment Transduction is the transfer of DNA by bacteria-specific viruses called bacteriophage Conjugation is the transfer of circular DNA called plasmids through cell to cell contact Horizontal DNA (gene) transfer is the exchange of genes between two cells of the same generation, as opposed to from parent to progeny  Virulence Factor (Mechanism of QS) QS – where bacteria “talk” to one another Autoinducers (signalling molecules – to measure population) bind to signalling receptors (on the surface or cytoplasm) becoming autoinducer/ receptor complex (ARC) Activate QS sensing genes ARC Multicellular population ARC activates the transcription of QS-controlled genes multicellular population When these autoinducers reach a critical, threshold level, they activate bacterial quorum sensing genes that enable the bacteria to behave as a multicellular population rather than as individual single-celled organism. The autoinducer/receptor complex is able to bind to DNA promoters and activate the transcription of quorum sensing-controlled genes in the bacterium. In this way, individual bacteria within a group are able to benefit from the activity of the entire group. https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Kaiser)/Unit_2%3A_Bacterial_Genetics_and_the_Chemical_C ontrol_of_Bacteria/3%3A_Bacterial_Genetics/3.2%3A_Bacterial_Quorum_Sensing%2C_Pathogenicity_Islands%2C_and_Secretion_Systems_(I njectosomes) Some pathogens are much more virulent than others Less cell numbers (102)of S. pneumoniae (Gram POS) killed 100% mice than high cell numbers S.p S.t (106)of S. typhimurium (Gram NEG) - S. pneumoniae more virulence than S. typhimurium Low dose of Strain A increases mortality than higher dose of Strain B - Strain A more virulence than Strain B https://slideplayer.com/slide/6281198/  In summary, pathogenicity vs. virulence Pathogenicity is the ability of an organism to infect a host and cause disease Aggressiveness is the ability of the pathogen to invade and establish within the host Virulence is the severity of the disease in infected hosts (or degree of pathogenicity) Ecological relationship https://www.thoughtco.com/commensalism-definition-and-examples-4114713  Normal flora vs. opportunistic mirobes Normal flora - microbes that colonize the body and usually do not cause disease. Opportunistic pathogens - microbes that normally do not cause disease, but may under certain circumstances.  Normal Flora microorganisms that live on another living organism (human or animal) or inanimate object without causing disease. *red – more resistant bacteria http://www.microbiologynutsandbolts.co.uk/normal-flora.html Opportunistic pathogen - harmless microbe that typically infects a host that is compromised in some way, either by a weakened immune system or breach to the body’s natural defences (skin, mucous membranes, tears, earwax, mucus, and stomach acid), such as a wound https://yakult.com.sg Quick think 1: Is human body sterile? No. We become colonised by bacteria from the moment we are born Quick think 2: What is the normally sites in the human body? Brain; Central nervous system Blood; Tissues; Organ systems Sinuses; Inner and Middle Ear Lower Respiratory Tract: Larynx; Trachea; Bronchioles (bronchi); Lungs; Alveoli Kidneys; Ureters; Urinary Bladder; Posterior Urethra Uterus; Endometrium (Inner mucous membrane of uterus ); Fallopian Tubes; Cervix and Endocervix Occurs when defect or breach in the natural defenses that creates a portal of entry Knowledge of the normal flora of the human body allows: Prediction of the pathogens causing infection as bacteria tend to grow in specific body sites e.g. Streptococcus pneumoniae from the upper respiratory tract causing pneumonia or Staphylococcus aureus from the skin causing intravenous cannula infections. Investigation for underlying abnormalities in specific areas of the body when bacteria are isolated from normally sterile sites e.g. Escherichia coli isolation from blood cultures indicates probable intra-abdominal pathology because Escherichia coli is part of the normal gastrointestinal flora, or isolation of a Viridans Streptococcus in blood cultures may indicate infective endocarditis as a result of poor dentition as Viridans Streptococcus are part of the normal mouth flora.  Brushing teeth linked to the lower risks of atrial fibrillation and HF. Malas gosok gigi selepas makan dan sebelum tidur menyebabkan pelbagai penyakit seperti penyakit jantung…  What is host-pathogen (microbe) interaction? Defined as how microbes sustain themselves within host organisms on a molecular, cellular, organismal or population level. Routes of transmission = https://www.sciencedirect.com/topics/immunology-and-microbiology/host-pathogen-interaction  Causes damage/ disease/ to the hosts: Host- pathogens pathogen interactions Hosts Hosts  Mechanisms of (bacterial) pathogenicity, virulence & toxigenicity Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. 1 2 3  Host Microbes (Pathogens) Interactions Direct: Direct contact Droplet Indirect: virulence vs. Host Resistant Airborne number of microbes able to fight off the Feco-oral infection before Vector borne Mechanical causes disease disease Biological signs/symptoms develop eyes, mouth, nose, or The expelling urogenital openings, of bacteria from the or through wounds or body. Important routes bites that breach the include the respiratory skin barrier tract, genital tract, and intestinal tract. A primary host that harbors the pathogen but shows no ill effects and serves as a source of infection  Adherence, Colonisation & Invasion Bacterial pathogens must be able to grab onto host cells or tissue, and resist removal by physical means (such as sneezing) or mechanical means (such as movement of the ciliated cells that line our airway). Adherence can involve polysaccharide layers made by the bacteria, such as a capsule or slime layer, which provide adhesion to host cells as well as resistance from phagocytosis. Adherence can also be accomplished by physical structures such as a pilus or flagellum. Once cells are successfully adhering to a surface, they increase in number, utilizing resources available at the site. This colonization is important for pathogen survival and invasion to other sites, which will yield increased nutrients and space for the growing population. Adhesion  Invasion Invasion refers to the ability of the pathogen to spread to other locations in the host, by invading host cells or tissue. It is typically at this point when disease or obvious signs/symptoms of illness will occur. While physical structures can still play a role in invasion, most bacterial pathogens produce a wide array of chemicals, specifically enzymes that effect the host’s cells and tissue. Enzymes such as collagenase, which allows the pathogen to spread by breaking down the collagen found in connective tissue. Or leukocidins, which destroy the host’s white blood cells, decreasing resistance. Hemolysins lyse the host’s red blood cells, releasing iron, a growth-limiting factor for bacteria. Bacteria in the bloodstream, a condition known as bacteraemia, can quickly spread to locations throughout the host. This can result in a massive, systemic infection known as septicaemia, which can result in septic shock and death, as the host becomes overwhelmed by the bacterial pathogen and its products.  bacteraemia septicaemia septic shock Septic shock is a life-threatening condition that happens when your blood pressure drops to a dangerously low level after an infection.  Invasion – cont. Once bacteria have successfully colonised their host, they need a way to invade these tissues in order to proliferate and cause disease. Invasion can be mediated by: Toxins which penetrate and damage cells, usually to aid the producing bacterium.  adhesion Successful establishment of infection by bacterial pathogens requires adhesion to host cells, colonization of tissues, and in certain cases, cellular invasion—followed by intracellular multiplication, dissemination to other tissues, or persistence. dissemination Toxins (VF)  Toxins (VF) Toxins are a very specific virulence factor produced by some bacterial pathogens, in the form of substances that are poisonous to the host. Toxigenicity refers to an organism’s ability to make toxins. For bacteria, there are two categories of toxins, the exotoxins and the endotoxins. 1. Exotoxins are heat-sensitive soluble proteins that are released into the surrounding environment by a living organism. There are many different bacteria that produce exotoxins, causing diseases such as botulism, tetanus, and diphtheria.  Toxins There are three categories of exotoxins: 1.Type I: cell surface-active – these toxins bind to cell receptors and stimulate cell responses. One example is superantigen, that stimulates the host’s T cells, an important component of the immune system. The stimulated T cells produce an excessive amount of the signalling molecule cytokine, causing massive inflammation and tissue damage. 2.Type II: membrane-damaging – these toxins exert their effect on the host cell membrane, often by forming pores in the membrane of the target cell. This can lead to cell lysis as cytoplasmic contents rush out and water rushes in, disrupting the osmotic balance of the cell (example pneumolysin (Ply) produced by S. pneumoniae). 3.Type III: intracellular – these toxins gain access to a particular host cell and stimulate a reaction within the target cell. One example is the AB-toxin – these toxins are composed of two subunits, an A portion and a B portion. The B subunit is the binding portion of the toxin, responsible for recognizing and binding to the correct cell type. The A subunit is the portion with enzymatic activity. Once delivered into the correct cell by the B subunit, the A subunit enacts some mechanism on the cell, leading to decreased cell function and/or cell death. An example is the tetanus toxin produced by the bacterium Clostridrium tetani. Once delivered to a neuron, the A subunit will cleave the cellular synaptobrevin, resulting in a decrease in neurotransmitter release. This results in spastic paralysis of the host. Each AB-toxin is associated with a different disease. Others include V. cholera toxins  Toxins – cont. 2. Endotoxins are made by Gram negative bacteria, as a component of the outer membrane of their cell wall. The outer membrane contains lipopolysaccharide or LPS. A massive release of endotoxin in a host can cause endotoxin shock, which can be deadly. Routes of transmission  Host Microbes (Pathogens) Interactions The transmission of microorganisms can be divided into: Exercise: Example of some microorganisms that can be transmitted by more than one route. Transmission Regardless of the reservoir, transmission must occur for an infection to spread. First, transmission from the reservoir to the individual must occur. Then, the individual must transmit the infectious agent to other susceptible individuals, either directly or indirectly. Pathogenic microorganisms employ diverse transmission mechanisms. Contact transmission includes: direct contact (person-to-person). e.g. touching, kissing, sexual intercourse, or droplet sprays. indirect contact - involves inanimate objects called *fomites that become contaminated by pathogens from an infected individual or reservoir. *fomites - objects or materials which are likely to carry infection, such as clothes, utensils, and furniture. Contaminated doorknobs, towels, and syringes are all common examples of fomites https://courses.lumenlearning.com/suny-microbiology/chapter/modes-of-disease-transmission/ Vehicle transmission: refers to transmission of pathogens through vehicles such as water, food, and air. e.g. water contamination through poor sanitation methods leads to waterborne transmission of disease. dust and fine particles known as aerosols, which can float in the air, can carry pathogens and facilitate the airborne transmission of disease. https://link.springer.com/article/10.1007/s10867-020-09562-5 Transmission over distances greater than one meter is called airborne transmission. Tuberculosis is often transmitted via airborne transmission when the causative agent, Mycobacterium tuberculosis, is released in small particles with coughs. Tuberkulosis (TB) atau batuk kering In summary https://link.springer.com/article/10.1007/s10311-023-01579-1?fromPaywallRec=false Vector transmission: transmitted by a mechanical or biological vector, an animal (typically an arthropod) that carries the disease from one host to another. Mechanical transmission is facilitated by Biological transmission occurs when the a mechanical vector, an animal that carries a pathogen reproduces within a biological pathogen from one host to another without being vector that transmits the pathogen from one infected itself (food poisoning - diarrhoea, dysentery) host to another (malaria, dengue etc.) https://courses.lumenlearning.com/suny-microbiology/chapter/modes-of-disease-transmission/  You will learn some of these vectors in CSI153 https://courses.lumenlearning.com/suny-microbiology/chapter/modes-of-disease-transmission/  You will learn some of these vectors in CSI153 https://courses.lumenlearning.com/suny-microbiology/chapter/modes-of-disease-transmission/  You will learn some of these vectors in CSI153 https://courses.lumenlearning.com/suny-microbiology/chapter/modes-of-disease-transmission/ Exercise: Self-learning): 1. Barrier defences (skin, hair, mucus) 2. Internal defences (immune cells (cellular) defences) End of Lecture 2