Pathogenesis Of Bacteria PDF

PATHOGENESIS Of Bacteria Dr. Nada Abdallah Basheer Consultant microbiologist Pathogen: An organism that is capable of causing disease. Opportunistic organism rarely causes disease in immuno-competent people but can cause serious infection in immunocompromised patients. Virulence : is a qua...

PATHOGENESIS Of Bacteria Dr. Nada Abdallah Basheer Consultant microbiologist Pathogen: An organism that is capable of causing disease. Opportunistic organism rarely causes disease in immuno-competent people but can cause serious infection in immunocompromised patients. Virulence : is a quantitative measure of pathogenicity. Number of organisms required to cause diseases. Virulence The 50% lethal dose (LD50): is the number of organisms needed to kill half the hosts, and the 50% infectious dose (ID50) is the number needed to cause infection in half the hosts. Organisms with a lower LD50 (or ID50) are more virulent than those with a higher LD50 (or ID50) because fewer organisms are needed to cause death or disease. Infectious dose Number of organisms required to cause disease. Shigella and Salmonella both cause diarrhea but the infectious dose of Shigella is less than 100 organisms, whereas that of Salmonella is almost 100,000 organisms. The infectious dose of bacteria depends primarily on their virulence factors, e.g., pili, capsule, production of exotoxins,,,etc Infectious Diseases Occurs when microorganisms overpower the host defenses. The organism or its products present in sufficient amount to induce symptoms. The critical determinants are the number of organisms and their virulence. the main arms of the host defenses are innate and acquired immunity. Asymptomatic infections are common and recognized by detecting antibody against the organism in the patient's serum. Bacterial Infection Bacteria cause disease by three major mechanisms: Direct Invasion and inflammation. Toxin production: a) Exotoxin , polypeptides released by the bacteria. b)Endotoxin , lipopolysaccharides, part of the cell wall of Gm-ve bacteria. Immune - mediated mechanisms Types of Bacterial Infection Communicable infections, spread from host to host e.g; tuberculosis, contagious is highly communicable. Epidemic infection: occurs much more frequently than usual. Pandemic has a worldwide distribution. Endemic infection is constantly present at a low level in a specific population. Inapparent or subclinical infections that result in overt symptoms. Types of Bacterial Infection Some infections result in a latent state, after which reactivation of the growth of the organism and recurrence of symptoms may occur. Chronic carrier state, in which the organisms continue to grow with or without producing symptoms in the host. Normal flora are permanent residents of the body, it vary according to anatomic site. Colonization is the presence of a new organism that is neither a member of the normal flora nor the cause of symptoms. Stages Of Bacterial Pathogenesis 1. Transmission from an external source into the portal of entry. 2. Evasion of primary host defenses such as skin or stomach acid. 3. Adherenceto mucous membranes. 4. Colonization by growth of the bacteria at the site of adherence. 5. Disease symptoms caused by toxin production or invasion & inflammation. 6. Host responses; nonspecific & specific immuity. 7. Progression or resolution  Transmission Can be human-to-human or non-human sources (soil, water, and animals)or fomite source as towels. Mainly via respiratory tract, GIT , genital tract, blood transfusion and skin. Vertical transmission : through the placenta, during birth or breast milk. Horizontal transmission: person to person transmission. Animals can be a reservoir or a vector. Adherence to cell surfaces Pili, capsule & glycocalyces. Pili adhere to the surface of human cells enhancing the ability to cause diseases. E.coli & Neisseria gonorrhoeae E. coli with fimbriae Glycocalyx of S.epidermidis & St.viridans allow strong adherence to the endothelium of heart valves. Adherence to cell surfaces After attachment, bacteria often form a protective matrix "Biofilm" consist of polysaccharides & proteins, especially on prosthetic valves & IV catheters. it protect bacteria from antibiotics , antibodies and neutrophils. Important in the persistence of Pseudomonas in the lungs of cystic fibrosis & the formation of dental plaque & dental caries. Foreign bodies, predispose to infections, bacteria can adhere to these surfaces, but phagocytes adhere poorly due to the absence of selectins and other binding proteins on artificial surfaces  Invasion and inflammation Several enzymes play a role in pathogenesis: Collagenase & Hyaluronidase: degrade collagen and hyaluronic acid allows bacteria to spread through subcutaneous tissue; especially important in cellulitis. Coagulase accelerates formation of fibrin clot from fibrinogen, protect the bacteria from phagocytosis. (Staph.aureus) IgA protease. which degrades IgA allowing the organism to adhere to mucous membranes. (N. gonorrhoeae, H.influenzae, and St.pneumoniae). Leukcocidin destroys neutrophils & macrophages.  Invasion and inflammation Several virulence factors: The capsule prevents the phagocyte from adhering to the bacteria; anti-capsular antibodies allow more effective phagocytosis to occur (a process called opsonization) Cell wall proteins of the Gram-positive cocci, as the M protein of St.pyogenes (atiphagocytic) & protein A of S.aureus binds to IgG and prevents the activation of complement. Pili of Escherichia coli. Inflammation& intracellular survival Types of inflammation: a)Acute pyogenic infection; neutrophils predominate e.g. Pneumonia b)Chronic granulomatous infections; macrophages &T-cell predominate e.g. Tuberculosis infection. Intracellular survival is an important for certain bacteria enhances their ability to cause diseas, commonly cause granulomatous lesions.  Intracellular Parasites Obligate intracellular parasites (Chlamydia & Rickettsia) Many are facultative parasites (Mycobacterium, Legionella, Brucella, and Listeria). Mechanisms allow intracellularly survival: 1. inhibition of the fusion of the phagosome with the lysosome. 2. inhibition of acidification of the phagosome, which reduces the activity of the lysosomal degradative enzymes 3. escape from the phagosome into the cytoplasm, where there are no degradative enzymes.  Bacterial invasion The invasion of cells by bacteria depend on the interaction of specific bacterial surface proteins called invasins and specific cellular receptors. The movement of bacteria into the cell is a function of actin microfilaments. Once inside the cell, bacteria typically reside within cell vacuoles as phagosomes. Some remain there, others migrate into the cytoplasm, and some move from the cytoplasm into adjacent cells through tunnels formed from actin. Bacterial invasion The genes that encode many virulence factors in bacteria are clustered in pathogenicity islands on the chromosome, those encoding adhesins, invasins, and exotoxins are adjacent to each other on these islands Nonpathogenic variants do not have these pathogenicity islands. After bacteria have colonized and multiplied at the portal of entry, they may invade the bloodstream and spread to other parts of the body. Receptors for the bacteria on the surface of cells determine, in large part, the organs affected. Toxin production 1.Exotoxins: Secreated by both G+ve & G-ve bacteria , polypeptides in nature ,its gene is located in plasmids or bacteriophage (e.g diphtheria & cholera) Is one of the most toxic substance known. Toxoid is a toxin treated with formaldehyde acid or heat. Loses its pathogenicity but retains it’s immunogenicity. Used in vaccination. Toxins have A(the active)& B(binding) subunits. 2.Endotoxin Integral part of the cell wall of Gm-ve bacteria. Are lipopolysaccharides(LPS). Encoded on the bacterial gene. Produce fever, hypotension & shock. They are weakly antigenic. Have high mortality rate (30-50%).  Immunopathogenesis In rheumatic fever & acute glomerulonephritis, the symptoms of disease are due to the immune response to the presence of the organism. In rheumatic fever, antibodies are formed against the M protein of Str. pyogenes, which cross-react with joint, heart, and brain tissue. Inflammation occurs, resulting in the arthritis, carditis, and chorea that are the characteristic findings in this disease. Different Strains of Bacteria Produce Different Diseases bacteria that belong to the same genus and species can cause such widely divergent diseases. The different virulence factors are encoded on plasmids, on transposons, on the genome phages, and on pathogenicity islands. These transferable, extrachromosomal genetic elements accounts for the ability to cause different diseases. Virulence Factors Typical stages of an infectious diseases 1.Incubation period: the time between acquisition of the organism and the beginning of symptoms 2.Prodromal period: nonspecific symptoms occur. 3.The specific-illness period. 4.The recovery period. During which the patient either becomes a chronic carrier or goes into a latent period.  TH TH EN E AN TH K Y D EN E O U D