Basic Bacteriology III Lecture 7 PDF

Basic Bacteriology III BPM3: Lecture 7 Dr. Maria Ramos-Nino [email protected] 1  Terminology Normal Flora: endogenous microorganisms that live on another living organism without causing disease Pathogen: an organism that can cause disease Opportuni...

Basic Bacteriology III BPM3: Lecture 7 Dr. Maria Ramos-Nino [email protected] 1  Terminology Normal Flora: endogenous microorganisms that live on another living organism without causing disease Pathogen: an organism that can cause disease Opportunistic pathogen are usually non-pathogenic organisms that cause serious disease in immuno-compromised individuals or when in other locations Virulence Factors are bacterial features that contribute to infection Pathogenesis is the mechanism by which infections lead to symptoms When pathogenic bacteria meet the intestinal microbiota, Volume: 371, Issue: 1707, DOI: (10.1098/rstb.2015.0504) 5 SOM.MKII.BPM3.7.1.1.M.MB.13 Difference between true and opportunistic infections Normal Flora  Normal flora consist of all the microorganisms present in our body Microbiome refers to the microorganisms and their genes Microbiota refers to the microbes themselves  Example: An adult human body has approximately 2 m2 of skin, and it contains about 10^12 numbers of bacteria https://theconversation.com/the-human-microbiome-is-a- treasure-trove-waiting-to-be-unlocked-118757  Normal flora prevents the colonization of pathogens by competing with them for essential nutrients and attachment sites 6 SOM.MKII.BPM3.7.1.1.M.MB.12 Human Microbiota  Microbiome Initial colonization of bacteria occurs in primarily in the first year of life A healthy microbiome is highly diverse with beneficial bacteria Milani C, et al. (2017) The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 81:e00036-17. https://doi.org/10.1128/MMBR.00036-17 7 SOM.MKII.BPM3.7.1.1.M.MB.12 Human Microbiota  Microbiome Normal flora or microbiota vary in anatomic location and composition Ubiquitous on the skin, example Staphylococcus Very high numbers in intestine example Escherichia coli Absent in sterile sites (blood, organs….) 8 SOM.MKII.BPM3.7.1.1.M.MB.12 Human Microbiota  Microbiome  Loss of diversity leads to altered microbiota aka dysbiosis, and is associated with many health conditions Milani C, et al. (2017) The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 81:e00036-17. https://doi.org/10.1128/MMBR.00036-17 9 SOM.MKII.BPM3.7.1.1.M.MB.12 Human Microbiota Microbiome Impact in Health Example of dysbiosis Clostridiodes difficile infection Fecal Transplantation? Dysbiosis may lead to infections….. 10 SOM.MKII.BPM3.7.1.1.M.MB.12 Human Microbiota  Types of infections 1. Primary infection: Initial infection with an organism in the host. E.g., “Strep” throat 2. Reinfection: Subsequent infection by the same organism in the host (after recovery) Superinfections in COVID19 3. Secondary infection: An infection that follows on from, or is the indirect result of another infection. E.g., AIDS/Candidiasis (thrush) 4. Superinfection: Secondary infection that occurs during treatment of a primary infection. E.g., Enterococcus faecalis septicemia during treatment of E. coli urinary tract infection 5. Opportunistic infection (primary or secondary): cause by normally harmless bacteria that becomes pathogenic upon https://www.medpagetoday.com/infectiousdisease/covid19/86192 favorable changes in the environment. E.g., a) E. coli from feces entering the urinary tract. b) Lost of competition from other organisms due to use of antibiotics, Clostridioides 12 (Clostridium) difficile in the gut. SOM.MKII.BPM3.7.1.1.M.MB.13 Difference between true and opportunistic infections Example: Secondary infection https://www.sciencedirect.com/science/article/pii/S1931312810000363 13 SOM.MKII.BPM3.7.1.1.M.MB.13 Difference between true and opportunistic infections  Infection is dose-related https://basicmedicalkey.com/22-pathogenesis-of-bacterial-infections/ 15 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  VIRULENT FACTORS Adhesion Secretion (Adhesins) Factors (Secretion systems, Invasion Enzymes, Exotoxins, (Flagella) Resistance to Endotoxins) environment and host Immunity (Spores, Biofilms) A virulence factor is a molecule that enhances the ability of a microorganism to cause disease beyond that intrinsic to the species 16 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Appendages with Adhesin Properties Bacterial adhesins are attached to the tip of thin thread-like structures that are called pili or fimbriae They are of medical importance because they mediate the attachment of bacteria to mucosal or other surfaces (virulence factor) https://lookfordiagnosis.com/mesh_info.php?term=fimbriae%2C+bacterial &lang=1 https://basicmedicalkey.com/22-pathogenesis-of-bacterial-infections/ 17 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Adhesins Important for attachment to host tissue or abiotic surfaces FimH inhibitor Proanthocyanidins in cranberries FimH adhesin https://www.lifeextension.com/magazine/2014/6/the-dangers-of-using-antibiotics-to-prevent-urinary-tract-infections 18 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Flagella Associated with motility Contributes to virulence ex. penetrate mucus layer and aid with attachment Important for classification ex. Salmonella is motile, Shigella is not Recognized by the innate immune system Monotrichous Lopotrichous Amphitrichous Peritrichous http://textbookofbacteriology.net/structure_2.html 19 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Capsule Glycocalyx Slime Layer (not well organized) Capsule (well organized) Gelatinous sugar material including proteoglycans, glycoproteins, and glycolipids Functions to help the organism resist environmental insults Anti-phagocytic Asplenic individuals are vulnerable to sepsis. The majority of antibodies against capsule are produced in the spleen. 20 https://www.chegg.com/flashcards/test-2-cellular-components-of-acute-inflammation-260aba4f-e91f-4137-932c-00bb1789a54e/deck  Capsules and the immune system PAMPS Non-encapsulated organisms OR Encapsulated organisms Phagocyte Resistance to unenhanced Antibodies and Complement are phagocytosis important in dealing with https://bio.libretexts.org/ 21 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors encapsulated organisms Bacterial Endospores Formed during harsh environmental growth conditions Highly resistant to desiccation, chemicals, hot/cold temps due to spore coat of Dipicolinic acid Found in the environment Germinate into vegetative (replicating) bacterial cells on contact with moisture and suitable temp. and pH 2 Gram-positive genera form spores: Bacillus Clostridium 22 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors Bacillus anthracis Clostridium botulinum  23 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Biofilm Bacteria are sheltered from harmful factors in the environment, such as desiccation, antibiotics, and a host body's immune system. Slimy extracellular matrix produced by the bacteria Biofilm composed of extracellular polymeric substances (EPSs) 24 https://www.mdpi.com/1660-3397/9/10/2010 SOM.MKII.BPM3.8.1.2.M.MB.14 Microbial and host factors  Bacterial Secretion Systems Secretion Systems: Found in several Gram-negative bacteria. Important in the release of exotoxins, enzymes and effector proteins Type 3 Secretion System T3SS acts as a “needle” to inject effector proteins into host and modifying host cellular characteristics Ex. Salmonella inject effector proteins via T3SS to facilitate intracellular survival Changes in cell signaling (takes over the host) https://www.researchgate.net/publication/323249412_Some_current_concepts_in_antibacterial_drug_discovery 25 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Bacterial Enzymes  Enzymes to break down host tissues  Hyaluronidase which breaks down the connective tissue component  A range of Proteases  Lipases  DNAses  Hemolysins which break down a variety of host cells, including red blood cells. Promote invasion and dissemination 26 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Bacterial Toxins: Exotoxins Exotoxins: Toxins produced by bacteria that are secreted into the environment Produced by both Gram-positive and Gram-negative bacteria Types of exotoxins: AB Toxins (Type III toxin) Membrane disrupting toxins (Type II toxin) Superantigens (Type I toxins) Think cholera, tetanus, botulism 27 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes  Exotoxin: A/B-type Toxin 2 Components: A “active” subunit and B “binding” subunit B-subunit binds to specific host cell receptor, leading to internalization. A-subunit disassociates from B-subunit in host cell and targets cellular function. Ex. Cholera Toxin https://www.pinterest.co.uk/pin/643944446691380166/ 28 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Exotoxin: Membrane disrupting toxin Cytotoxin secreted by bacteria from local infection Toxin acts by forming pores in host cell membrane Cytotoxin causes localized inflammation and damage Ex. Staph aureus α-toxin causes Beta-hemolysis pattern on Blood agar Staphylococcus aureus 29 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes  Exotoxin: Super-antigen (exotoxin) Super-antigen: Non-specific activation of T cells leads to massive cytokine release, causing Toxic Shock Ex. Staph aureus Toxic Shock Syndrome Toxin https://lookfordiagnosis.com/mesh_info.php?term=Superantigens&lang=1 30 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Bacterial Toxins: Exotoxins  Types based on the host they attack: Enterotoxins: found in the intestinal mucosa (e.g., in the pathogenesis of Vibrio cholera) Neurotoxins: which occur in nerve tissues where they cause neurological damages (e.g., in the pathogenicity of Clostridium tetani) Cytotoxins: which are normally found in the general tissues of the body where they cause a series of local and systemic damages (e.g., in the pathogenicity of Staphylococcus aureus) 31 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes  Notable Exotoxins https://www.slideshare.net/timtim1391/fat2chapter15-pathogenicity 32 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Temperate Phage Lysogenic conversion: spread of virulent factors (example: exotoxins) 33 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Bacterial Toxins: Endotoxins Endotoxins are microbial toxins which are produced only on cell lysis (cell death) They are lipopolysaccharide (LPS) components of the outer membrane of Gram-negative bacteria Endotoxins produce their effect in a host by activating the complement system by the alternative pathway They are pyrogenic in action (i.e., they produce fever in their host). They can cause bacterial sepsis (shock) and intravascular coagulation Think meningococcemia, sepsis 34 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Bacterial Toxins: Endotoxins 35 SOM.MKII.BPM3.7.1.1.M.MB.16 Damage from microbial exotoxins and enzymes Pathogenicity Multi-step Disease Process https://oncohemakey.com/immunity-to-bacteria-and-fungi/ Chronic –persistence Acute 37 Adapted from Microbiology Pearson Education 4ed, Figure 14.10 SOM.MKII.BPM3.8.1.2.M.MB.L7.14 Microbial and host factors Disease Process: Outcomes Acute – finite duration of time of infection and symptoms, resulting in resolution Transient carrier – finite duration and absence of symptoms with low infections Chronic latent –long duration of time and not display of any symptoms of disease Chronic persistent –long duration of time and experiences continuous symptoms Chronic recurrent – long duration of time and symptoms will exacerbate and abate, often as a result in the change of a person’s immune status Acute Transient Carrier Bacterial load Chronic latent Chronic Persistent Chronic Recurrent Bacterial load 38 SOM.MKII.BPM3.8.1.2.M.MB.L7.14 Microbial and host factors