Microflora & Bacetrial Virulence PDF

Normal flora types Microbial Flora & Bacterial ⚫1- Resident Pathogenesis 2- Transient ⚫Resident populations: normal flora, microb...

Normal flora types Microbial Flora & Bacterial ⚫1- Resident Pathogenesis 2- Transient ⚫Resident populations: normal flora, microbiota, indigenous microbial population, microflora, microbial flora Vast majority of normal flora are bacteria. - Internal tissues normally sterile. Resident flora What is Normal Flora ? ⚫Resident flora: The microorganisms that usually occupy These are mixture of microorganisms regularly found at any a particular body site are called the resident flora. anatomical site on/within the body of a healthy person. Bacteria of the resident flora outnumber a person's own cells 10 to 1. The normal flora prevent colonization by pathogens by competing for attachment sites or for essential nutrients. ⚫ If disturbed through environmental influences, it promptly This is thought to be their most important beneficial effect, reestablishes itself, otherwise disruption of the which has been demonstrated in the oral cavity, the intestine, microbiota may compromise immune function, leading to the skin, and the vaginal epithelium. increased susceptibility to infectious disease.  Transient flora Normal flora ⚫Non‐pathogenic or potentially pathogenic microorganisms that inhabit the skin or mucous membranes for hours, days, or ⚫Human body weeks. ⚫1013 cells ⚫Microorganisms that colonize people for hours to weeks but do not establish themselves permanently are called transient ⚫1014 bacteria flora. ⚫Derived from the environment, does not produce disease ⚫Does not establish itself permanently on the surface How much of your body weight is bacteria? This includes bacteria, fungi and viruses, which reach the hands, for example, The human body contains trillions of microorganisms — outnumbering human by direct skin-to-skin contact or indirectly via objects. Transient flora are cells by 10 to 1. Because of their small size, however, microorganisms make up found on the outer layers of skin and are fairly easily removed by only about 1 to 3 percent of the body's mass, but play a vital role in human handwashing. The resident flora are more deeply attached to the skin and health. are harder to remove. Relationship between normal flora and host Normal flora ⚫Some bacteria occupy more than one niche. ⚫Some bacteria occupy only one niche: tissue tropism. ⚫Tropism is the phenomenon by which bacteria are restricted to certain hosts, tissues and cell types. ⚫Tropism determined by bacterial ligand-host receptor interactions. ⚫Combinations of microflora at same site. The human cannot digest all of the food that he eats. The bacteria eat the food that the human cannot digest and partially digest it, allowing the human to finish the job. The bacteria benefit by getting food, and the human benefits by being able to digest the food it eats -> Mutualism Where is the Normal Flora Found? NORMAL FLORA‐ Skin ⚫ Skin SITE COMMON/ LESS COMMON BUT MEDICALLY NOTABLE ORGANISMS ⚫ Conjunctiva IMPORTANT ⚫ Nasopharynx ORGANISMS Cutaneous surfaces Staphyloccocus Staphyloccocus aureus, ⚫ Oral cavity including urethra and outer ear epidermidis Corynebacteria (diphteroids) ⚫ Gastrointestinal Streptococci, Anaerobes e.g. tract and rectum Peptostreptococci, ⚫ Urogenital tract Yeast (Candida sp.) Staphylococcus epidermidis, invariably found on skin and nasal membranes. Bacterial Flora in a normal person Normal flora - Skin ⚫Staphylococcus epidermidis: Major inhabitant making up more than 90% of the flora. ⚫Staphylococcus aureus: Nose, vulvar skin ⚫Occurrence in nasal passages varies with age being greatest in newborns, less in adults. Factors that are Important in Eliminating Non‐resident microorganisms from the Skin Normal flora - Conjunctiva 1. Low pH ⚫Variety of bacteria: low numbers present ⚫High moisture 2. Fatty acids (sebaceous secretions) 3. Lysozyme ⚫Blinking mechanically removes bacteria ⚫Lachrymal secretions include lysozyme Neither profuse sweating nor washing and bathing can eliminate or significantly modify the normal Lysozyme is a naturally occurring enzyme found in bodily resident flora secretions such as tears, saliva, and milk. It functions as an antimicrobial agent by cleaving the peptidoglycan The prime target of FA action is the cell membrane, where FFAs disrupt component of bacterial cell walls, which leads to cell death. the electron transport chain and oxidative phosphorylation. Normal flora of the skin: Normal flora – UPPER RESPIRATORY TRACT SITE COMMON/ LESS COMMON BUT MEDICALLY NOTABLE ORGANISMS IMPORTANT Benefit Harm ORGANISMS ⚫Inhibit fungal growth ⦁ Body odor ⚫Prevent transient NOSE Staphyloccocus aureus Staphyloccocus ⦁ Acne epidermidis, Corynebacteria pathogenic organisms from ⦁ Opportunistic (diphteroids) colonizing the skin surface, infections Assorted Streptococci, either by competing for nutrients, secreting Oropharynx Viridans streptococci Assorted streptococci, chemicals against them, or including Streptococcus nonpathogenic Neisseria, mutans stimulating the skin's Haemophilus influenzae immune system  Normal flora - Oral cavity Normal flora - Respiratory tract ⚫Ecology and developmental stages ⚫Lower respiratory tract ⚫Birth: sterile mouth within 4-12 hours (lactobacilli, streptococci) (trachea, bronchi, pulmonary tissues) ⚫Neonate (Streptococcus salivarius, Staphylococci, ⚫Usually sterile Neisseriae, Moraxella catarrhalis ⚫Ciliated epithelium ⚫Teeth appear (Streptococcus mutans, ⚫Mucus blanket: entrapment Streptococcus parasanguis) ⚫Alveolar macrophages ⚫Gingival crevice area (Anaerobic species, yeasts) ⚫If breached: opportunistic ⚫Puberty (Bacteroides, spirochetes) infections ⚫108 bacteria/mL of saliva; potentially >700 species Normal flora of the oral cavity Normal flora - Gastrointestinal tract ⚫GI ecology varies ⚫ Large intestine Benefit Harm ⚫Compete with ⚫ Plaque formation and ⚫ 109-1011/ml pathogens for ⚫Esophagus saliva ,food dental disease ⚫ >350 species colonization ⚫Stomach harsh 102 ⚫ ⚫Small intestine (103 - sites E. coli = 0.1% of total population ⚫Produce substances ⚫ Primarily anaerobic 108) ⚫ that inhibit Facultative aerobes deplete oxygen pathogens ⚫Proximal small ⚫ Adult excretes 3x1013 ⚫Stimulate intestine (duodenum bacteria/day local and jejunum) ⚫ 25%-35% of fecal mass = bacteria immunity ⚫Distal small intestine (ileum)  Normal flora - Gastrointestinal tract Normal flora of GI tract: SMALL INTESTINE streptococci, lactobacilli, enterococci, enterics, anaerobic rods and cocci Location (adult) Bacteria/gram contents Benefit Harm ⚫ Production of vitamins and ⚫ Possible relationship with duodenum 103-106 nutrients ⚫ Competition with jejunum and ileum 105-108 inf lammatory conditions cecum and transverse pathogens for colonization ⚫ Transfer antibiotic 108-1010 colon resistance to pathogens sites ⚫ Production of substances sigmoid colon and 1011 rectum that inhibit pathogens Normal flora of GI tract: LARGE INTESTINE Normal flora of GI tract – stomach Bacteroids, clostridia, bifidobacteria, lactic acid Helicobacter pylori bacteria, enterococci, enterics Harm Benefit Harm ⚫ Causes gastric ulcers ⚫ Competition with ⚫ Relationship with pathogens for inflammatory ⚫ Probable association with colonization sites bowel diseases duodenal ulcers ⚫ Production of ⚫ Production of Helicbacter pylori substances that carcinogens and - After H. pylori enters your body, it attacks the lining of your stomach, inhibit pathogens relationship with colon which usually protects you from the acid your body used to digest food. ⚫ Stimulate cancer Once the bacteria have done enough damage, acid can get through the development and ⚫ Methanogenesis activity of immune lining, which leads to ulcers. system There is enough evidence to suggest that H. pylori is also beneficial. Infection A strong association between methanogens' presence and chronic with H. pylori is asymptomatic in approximately 85% of individuals, while 15% constipation in humans was shown. Methane was shown to slow intestinal develop symptomatic peptic ulcer disease, and less than 1% go on to develop transit by 59%, and thus may contribute substantially to constipation. gastric cancer  Normal flora - Urogenital tract Normal flora of the VAGINA - during child-bearing age lactobacilli and other lactic acid bacteria ⚫Upper urinary tract (kidneys, ureters, bladder) usually sterile ⚫Male anterior urethra contains the same microorganisms Benefit Harm as the skin, enteric and enterococcus ⚫Competition with ⚫none ⚫Vagina: complex microbiota pathogens for ⚫At birth Same as mother (PH 5) colonization sites ⚫Neonate Same as skin+enteric+ streptococcus (PH 7) ⚫Production of lactic acid ⚫At puberty Lactobacillus+same as skin+ that inhibits pathogenic bacteria and anaerobes+ streptococcus (PH 5) yeasts ⚫At menopause: return to prepuberty flora The vaginal microbiota (VMB) What are the roles of Normal Flora: The vaginal microbiota (VMB) are defined as a community of 1. Immunostimulation commensal, symbiotic and pathogenic microorganisms that They produce antibodies which may colonize the vagina. In the majority of healthy reproductive age contribute to host defenses. women, the VMB is dominated by lactobacilli; although these bacterial communities can vary considerably between individuals and over time. 2. Protection from External Invaders Because of the normal flora occupy body’s epithelial surfaces, they are able to prevent other The vagina's pH level is about 3.8 to 4.5, which means it's on bacteria from establishing themselves by the acidic side. Its acidity slightly decreases as you get older, blocking receptors (attachment), competing for with its pH level rising closer to 5. essential nutrients or producing anti-bacterial substances. e.g. Fatty acids, peroxides , Bacteriocins.  What are the roles of Normal Flora: What are the negative roles of Normal Flora: 1) Production of Carcinogens: Some normal flora may 3) Nutrition modify, through their enzymes, some chemicals in our Some of the normal intestinal flora e.g. E. coli & diets into carcinogens Bacteroids produce Vitamin K in the gut which is e.g. Artificial sweeteners may be enzymatically modified into available for use by host. bladder carcinogens. 4) Stimulate development of certain tissues: Predominant and important flora of various body sites in lymphatic tissues (Peyer’s patches) in GI tract and normal health. influence immunology of gut-associated lymphatics 2) May be a source of opportunistic infections e.g. In-patients with impaired defense Mechanisms Overall harmful effects of the normal flora Overall benefits of the normal flora ⦁ Synthesis and excretion of vitamins used by the host ⚫Competition with host for nutrients ⦁ Competition with pathogens for nutrients and colonization sites ⚫Bacterial synergism between normal flora and ⦁ Direct antagonism against pathogens potential pathogens ⦁ Stimulate the development of immunological tissues ⦁ Stimulate the activity of the immune system by ⚫Endogenous disease and opportunistic infection production of natural antibodies  Opportunistic flora Normal flora - Risks and Opportunistic ⚫Some normal flora become opportunistic pathogens ⚫ (Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, Streptococcus pneumoniae, Pseudomonas aeruginosa, etc.) ⚫Breach of skin/mucosal barrier: trauma, surgery, burns Sepsis is the body's extreme response to an infection. It is a life-threatening medical emergency. Sepsis happens when an infection ⚫Bacteria at you already have triggers a chain one site may be commensal, but might be reaction throughout your body. pathogenic at another site Pneumonia is an infection that inflames your lungs' air sacs (alveoli). Probiotics/Prebiotics Opportunistic flora ⚫ Probiotic ⚫ Oral administration of living organisms to promote health ⚫Growth of commensals may put patient at risk: Broad- ⚫ Mechanism speculative: competition with other bacteria; stimulation of nonspecific immunity spectrum antibiotic therapy decreases total number of ⚫ Species specific: adherence and growth (tropism) bacterial in gut. ⚫During repopulation, faster-growing aerobic ⚫ Prebiotic Enterobacteriaceae over slower-replicating anaerobes ⚫ Non-digestible food that stimulates growth or activity of GI increases probability of gram-negative bacteremia microbiota, especially bifidobacteria and lactobacillus ⚫Cross-reactive responses to host tissue: Superantigen bacteria (both of which are noninflammatory) ⚫ Typically a carbohydrate: soluble fiber ⚫Chronic, low-grade inflammation ⚫Perturbation of cytokine network  Guide to the Normal Bacterial Flora of Humans Guide to the Normal Bacterial Flora of Humans Staphylococci Streptococci ⚫ Includes Staphylococcus epidermidis and ⚫Includes Streptococcus Staphylococcus aureus salivarius, S. mitis and S. mutans ⚫ Located on skin ⚫Located in oral cavity and most mucous membranes Staphylococcus epidermidis, invariably found on skin and nasal membranes. Streptococcus mutans, the main bacterium implicated in dental caries. Guide to the Normal Bacterial Flora of Humans Guide to the Normal Bacterial Flora of Humans Corynebacteria Lactic acid bacteria ⚫Includes Corynebacterium and ⚫Includes Streptococcus Probionibacterium and Lactobacillus species species ⚫Located primarily ⚫Located in oral on skin and upper cavity, intestinal Propionibacterim acnes colonies. The Lactobacillus acidophilus and a vaginal respiratory tract bacterium is found on skin, nasal tract and vagina squamous epithelial cell. membranes and the conjunctiva of the eye.  Guide to the Normal Bacterial Flora of Humans Why don’t we get ill? Enterococci i. The entire invading population is killed by phagocytic cells, such ⚫Includes Enterococcus as neutrophils, or circulating bactericidal compounds, such as faecalis and complement proteins of the immune system. Enterococcus faecium ii. the density of bacteria traversing the integument is collectively too low to condition the tissue to allow their population to grow. ⚫Located in iii.The mutations or phase shifts required to get across the mucosa the intestinal or survive in the blood do not occur. tract Enterococcus faecalis ‐ so regularly found in the intestine that some countries use the bacterium as their indicator of fecal pollution of water. Guide to the Normal Bacterial Flora of Humans Bacterial Pathogenesis Enteric bacteria ❖A pathogen is a microorganism that is able to cause disease in a plant, animal or insect. ⚫Gram‐negative rod‐ ❖Pathogenicity is the ability to produce disease in shaped bacteria a host organism. including E. coli and ❖Microbes express their pathogenicity by means its relatives of their virulence, a term which refers to the degree of pathogenicity of the microbe. ⚫Located in the intestinal tract ❖Determinants of virulence of a pathogen are any of its genetic or biochemical or structural Escherichia coli Gram stain and colonies features that enable it to produce disease in a on EMB agar. host. Bacterial Pathogenesis Mechanisms of Bacterial Pathogenicity ❖The relationship between a host and a pathogen is 1.Invasiveness: the ability to invade tissues. dynamic, since each modifies the activities and functions Encompasses mechanisms for: of the other. ❖The outcome of such a relationship depends on: ❖Colonization (adherence and initial - The virulence of the pathogen multiplication). - The relative degree of resistance or susceptibility ❖Production of extracellular substances which of the host, mainly due to the effectiveness of the host facilitate invasion (invasins) defense mechanisms. ❖Ability to bypass or overcome host defense mechanisms. Animals and microbes Mechanisms of pathogenicity 2. Toxicogenesis: ability to produce toxins. ❖Normal flora (beneficial) : ❖Bacteria may produce two types of toxins: - GI track, skin, upper respiratory track i. Exotoxins ❖Virulent bacteria (actively cause disease ) : ii. Endotoxins. - pathogenic islands ❖Exotoxins are released from bacterial cells and may act at tissue sites removed from the site of Opportunistic bacteria ( when host wish bacterial growth. underline problem ) : ❖Endotoxins are cell-associated substance. ( classic - pseudomonas acruginosa : cystic fibrosis/ burn sense, endotoxin refers to the lipopolysaccharide - TB, Kaposi’s sarcoma ( herpesvirus ) : AIDS component of the outer membrane of Gram- negative bacteria ). Mechanisms of Bacterial Pathogenicity Infection/entry of pathogens ❖Ingestion (fecal-oral): Salmonella , Shigella, Vibrio, ❖Endotoxins may be released from growing Clostridium etc… bacterial cells and that are lysed as a result of ❖Inhalation (respiratory): Mycobacterium, Mycoplasma, effective host defense ( e.g. lysozyme ) or the Chlamydia etc… activities of certain antibiotics ( e.g. penicillin's ❖Arthropod bite (mosquito, flea, tick, Tsetse fly ) and cephalosporin's ). ❖Sexual transmission: HIV ❖Hence, bacterial toxins, both soluble and cell- ❖Iatrogenic ( needle stick, blood transfusion ) associated, may be transported by blood and ❖Maternal-neonatal: HIV lymph and cause cytotoxic effects at tissue sites. ❖Some bacterial toxins may also act at the site of colonization and play a role in invasion. Bacterial pathogenesis Modes of infectious disease transmission ❖Contact transmission ❖Infection/ entry - Direct contact ( person-to-person ) : syphilis, gonorrhear, ❖Virulence factors herpes - Indirect contact ( fomites ) ❖Pathogenesis - Droplet ( less than I meter ) : whooping cough, strep throat ❖Escape of immune ❖Vehicle transmission surveillance - airborne : influenza, tuberculosis, chickenpox - Water-borne ( fecal-oral infection ) : cholera, diarrhea - Food-borne : hepatitis, food poisoning, typhoid fever ❖Vector transmission - Biological vectors Extracellular versus Intracellular Parasitism Barrier systems ❖Extracellular parasites - destroyed when phagocytosed. - damaging tissues as they remain outside cells. - inducing the production of opsonizing antibodies, they usually produce acute disease of relatively short duration. ❖Intracellular parasites - can multiply within phagocytes. - frequently cause chronic disease. The environment in a cell Virulence factors Cytosol pH=7 Factors enhancing the ability of bacteria to cause Phagosome pH=6 Phagolysosome pH=5 disease - Adhesin: attachment - Exotoxin A: inhibits host protein synthesis - Exoenzyme S: interferes with phagocytic killing - Phospholipase C: damage tissue - Pyocyanin: damages tissue by ROS - Antibiotic resistance: complicates therapy  Pathogenic action of bacteria Endotoxins Tissue destruction: flesh-eating bacteria Toxins: bacterial components that directly harm tissue or - formed from cell (Gram negative bacteria) trigger disease symptoms. - bound lipopolysaccharides that are usually released - Endotoxin: lipopolysaccharides upon lysis of the bacterial cell; the lipid component is - Exotoxin: A-B toxins the main toxin. Superantigens - leads to fever in the host by stimulating endogenous pyrogens (fever-inducing substances usually derived - Immunopathogenesis: from microorganisms.) - less toxic than exotoxins; - Excess immune responses - in contrast to exotoxins, the endotoxins are not - Autoimmunity destroyed by heating. A-B toxins A-B toxins have two components (initially linked together). One binds to host receptor, the other enters and damages the cell- Secretion of toxins Superantigens Bacteria can damage the host tissues by either exotoxins and endotoxins Superantigens are unusual bacterial toxins that interact with exceedingly large numbers of T4- lymphocytes. They bind to the surface of the target cell but do not enter the cell. Superantigens interact with antigen-presenting cells (APCs) and T cells to induce T cell proliferation and massive cytokine production, which leads to rash, capillary leak, and subsequent hypotension, the major symptoms of toxic shock syndrome. Evasion Strategies Superantigens