Week 3 Lec 1.pdf

A BAD DAY AT THE OFFICE A work lunch that almost resulted in death! Started with acute vomiting, headache and fainting followed by severe diarrhea and delirium ICU for a week – multiple organ shut-down within 24 hours of onset 5 week recovery in hospital and months at home...

A BAD DAY AT THE OFFICE A work lunch that almost resulted in death! Started with acute vomiting, headache and fainting followed by severe diarrhea and delirium ICU for a week – multiple organ shut-down within 24 hours of onset 5 week recovery in hospital and months at home 1  BIOL341/982 Infection and Immunity Interactions of Microbes with the Host: Colonisation and Survival Mechanisms Prof. Martina Sanderson- Smith [email protected] 2 A BALANCING ACT Microbe Factors Microbe burden 3  A BAD DAY AT THE OFFICE: Shigella dysenteriae Produces shiga toxin = one of the most toxic and lethal toxins known 4 MICROBIAL COLONISATION Lecture 5 outline Colonisation, attachment and invasion survival 5  ENTRY AND EXIT § Pathogens enter and exit the host through portals § Portal of entry: Refers to the site at which the pathogen enters the host §Varies considerably between organisms, and is a key factor in the establishment of disease § Portal of exit: Refers to the site from which the pathogen is able to leave the body after the end of its pathogenicity cycle § Easy transmission enables organism to continue its pathogenic existence § Shed in large numbers in secretions and excretions § Present in the blood for uptake – e.g. blood sucking arthropods 6  COLONISATION § Colonisation is the establishment of a stable microbial population in the host § Attachment to host cells plays a major role in colonisation § First step in development of an infectious disease § Primary sites of colonisation include: § Respiratory tract § Intestinal tract § Reproductive tract § Urinary tract § Skin, mucosa 7  COLONISATION § Host organisms have developed many ways to try and prevent microbial colonisation: Type of Host Defences Microbial Evasion Mechanism Examples Infection Respiratory tract Mucociliary clearance Adhere to epithelial cells, interfere with ciliary Influenza virus action Alveolar macrophage Replicate in alveolar macrophage Legionella, tuberculosis Intestinal tract Mucus, peristalsis, acidic Adhere to epithelial cells, Resist acid, bile Rotavirus, environment, bile, gut Salmonella, flora Helicobacter pylori Reproductive Flushing action of urine Adhere to urethral/vaginal epithelial cells Gonococcus, tract and secretions, mucosal Chlamydia defences Skin, mucosa Layers of constantly Invade skin/mucosa Measles shed cells (mucosa), Penetrate intact skin Staphylococci Dead keratinised skin layers Streptococci 8  POST-COLONISATION § Some pathogens remain at the site of infection, whereas others invade host tissues Bacterial pathogens restricted to epithelial surfaces include: Respiratory tract Urogenital tract Skin Intestinal tract Mycoplasma pneumoniae Neisseria gonorrhoeae Staphylococcus aureus Salmonella enterica (Atypical pneumonia) (Gonorrhea) (Skin infections) (Food poisoning) Bordetella pertussis Proteus mirabilis Streptococcus pyogenes Shigella spp. (Whooping cough) (Urinary tract infection) (Impetigo) (food poisoning) Corynebacterium Escherichia coli Campylobacter jejuni diptheriae (Diphtheria) (Urinary tract infection) (Food poisoning) Streptococcus pyogenes Vibrio cholerae (Pharyngitis) (Cholera) Escherichia coli (Food poisoning) 9  POST-COLONISATION § Post-colonisation, some pathogens remain at the site of infection, whereas others invade host tissues Bacterial pathogens that cross epithelial surfaces include: Respiratory tract Urogenital tract Skin Intestinal tract Mycobacterium Treponema pallidum Bacillus anthracis Salmonella typhi tuberculosis (TB) (syphilis) (anthrax) (Typhoid fever) Yersinia pestis Streptococcus pyogenes (plague) (Necrotising fasciitis) Legionella pneumophila (Legionnaire’s) 10  VIRAL ATTACHMENT TO HOST CELLS AND TISSUES Viruses gain access to host cells by binding to specific receptors expressed on the surface of host cells. 11 VIRUSES HAVE A HOST RANGE AND TISSUE SPECIFICITY § A host range refers to what organisms the virus can infect and depends on capsid or envelope structure. § Many viruses infect certain cell or tissue types within the host (tissue tropism). § The virus needs a specific receptor to invade the host cell. 12 VIRAL ATTACHMENT TO HOST CELLS AND TISSUES: Adenovirus § Adenoviruses are a double-stranded DNA virus and a major cause of human respiratory disease § 7 human species and over 50 serotypes § Found in mammals, birds and amphibians § Attach via a Penton fibre: § Projects from each apex § Consist of a slender shaft § Globular head § Different adenovirus subtypes attach to different receptors 13 14 BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES § Bacterial adhesins: surface structures that bind to specific host receptors § Fimbrial/pilus adhesins § Afimbrial adhesins (capsule/protein adhesins) § “Lock and key" mechanism § Overcome electrostatic repulsion (bacterial and host cells are both negatively charged) fimbrial/pilus adhesins afimbrial adhesins 15  BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES: Fimbrial Adhesins § Bacterial fimbriae/pili: § Hair-like structures 5-7nm diameter with varied morphology § Structurally diverse and different fimbriae recognise different host receptors § Comprised primarily of protein subunits called pilin “Bald” E. coli Bundle-forming pili CS1-piliated (non-pathogenic) enteropathogenic E. coli enterotoxigenic E. coli (ETEC) (EPEC) 16  BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES: Fimbrial Adhesins § Shaft - repeating protein subunits (pilins) assembled into a helical array § Adhesive subunit(s) § Specialised tip structure (Pap pili – UPEC) § Recognise specific cells e.g. bladder and kidney cells § No specialised tip structure (N. meningitidis). § Adhesive subunits along length of shaft § Interact with cells via multiple anchorage points Pap (pyelonephritis associated pili) associated with uropathogenic E. coli (UPEC) which causes UTIs (bladder, kidney infections)....... 17  BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES: Fimbrial Adhesins Type 1 pilus-mediated UPEC attachment to bladder epithelium UPEC Bladder epithelium Mulvey M A et al. PNAS 2000;97:8829-8835 18  BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES: Fimbrial Adhesins Host and tissue types specified by some E. coli fimbriae: Fimbriae/Pili Host/Tissue Disease Enterotoxigenic E. coli (ETEC) K88 Pig / intestine Diarrhoea K99 Cow, sheep, pig / intestine Diarrhoea CS1 Human/ intestine Diarrhoea Enteropathogenic E. coli (EPEC) Bundle-forming pili (Bfp) Human/ intestine Severe diarrhoea (children) Uropathogenic E. coli (UPEC) Pap Human/Urinary tract Urinary tract infections Type1 non-specific Urinary tract infections Extraintestinal pathogenic E. coli (ExPEC) ExPEC pili Human infant brain, kidney, Meningitis, septicaemia epithelium 19 BACTERIAL ATTACHMENT TO HOST CELLS AND TISSUES: Afimbrial Adhesins Afimbrial adhesins: contribute to tighter binding after pilus anchorage Dehio et al, 1998 Trends Microbiol. 6: 489-495 20  INTRACELLULAR PATHOGENESIS Why intracellular? § Immune evasion § Nutrient rich (in the cytoplasm) § Transport around the body Intracellular survival (olpaimages.nsf.gov/admin/images/listerias.jpg) § Subverting intracellular antimicrobial mechanisms such as phagosome- lysosome fusion, modulating phagosomal pH, damaging phagosomal membranes, and/or quenching microbicidal oxidative bursts § Escape from the phagosome to the cytoplasm § Replicate 21  BACTERIAL TISSUE INVASION § Invasiveness is the ability of a pathogen to invade tissues § Invasiveness encompasses: § Mechanisms for colonisation (adherence and initial multiplication) § Production of extracellular substances ("invasins"), that promote the immediate invasion of tissues – “spreading factor” § Ability to bypass or overcome host defence mechanisms which facilitate the actual invasive process 22 SUCCESSFUL INFECTION OFTEN DEPENDS ON A VARIETY OF ENZYME VIRULENCE FACTORS § Pathogens have to adapt to a new environment when they enter a host. § Enzymes can help pathogens resist body defenses.. 23  BACTERIAL TISSUE INVASION: Staphylococcus Clot formation contributes to staphylococcal skin boil 24 Pommerville Fig 20.8  BACTERIAL TISSUE INVASION: Staphylococcus § Some staphylococci produce coagulase to form a blood clot that protects them from phagocytosis. Figure 20.8A: Enzyme virulence factors. 25  BACTERIAL TISSUE INVASION: Staphylococcus § Hyaluronidase enhances pathogen penetration through tissues. § It digests hyaluronic acid, which binds cells together in a tissue. § Important for several streptococci and staphylococci. § Often leads to widespread destruction of connective tissue. Figure 20.8B: Enzyme virulence factors. 26  BACTERIAL TISSUE INVASION: S. pyogenes Haemolysin: § Group of enzymes that dissolve RBC’s § Combines with the membranes of erythrocytes producing pores § RBCs lyse and cytoplasmic contents spill out WHY???? § Lysing RBCs releases iron (in haemoglobin) § Bacteria need iron for metabolism, and In the laboratory the production of haemolysin and the only source of iron in humans is in haemolysis can be observed by the destruction of blood cells in a blood agar medium RBC’s. Eg. S. pyogenes 27  BACTERIAL TISSUE INVASION: S. pyogenes DNase § Production of streptodornase (DNase) allows S. pyogenes to evade capture by neutrophil extracellular traps (“DNA NETs”) – by digesting the NETs Bacterial capture by DNA NETs is part of the innate immune response to infection. Brouwer et al, Nature Comms (2020) 28 KNOWLEDGE LEVEL REQUIRED FOR BIOL341 Modes of transmission Colonisation – methods Attachment – viral and bacterial Bacterial Invasion – methods 29  DEFINITIONS Transmission is the passing of a disease from an infected individual or group to a previously uninfected individual or group. Colonisation is the establishment of a stable microbial population in the host, and is the first step in development of an infectious disease. Intracellular invasion is the entry of host cells by microbial pathogens and survival therein. Intracellular survival may allow immune system avoidance, transport throughout the host (e.g.. macrophages) or latent infection. Tissue invasion is the penetration of host tissues by microbial pathogens allowing entry into deeper tissues, the systemic system or other host compartments. 30