What is the Microbiome?
Collection of genomes of all the microorganisms found in a particular environment
What is the Human Microbiome?
Collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, & viruses) that live inside/on the human body.
What is the collection of microbial genomes that contribute to the broader genetic portrait?
Metagenome
"The human body is a Supraorganism," means what?
Collection of human & microbial cells & genes = blend of human & microbial traits
What is the difference between Commensal & Mutualistic relationships?
Commensal coexists without harming humans & Mutualistic means they both benefit
What is the Human microbiome project (HMP)?
Founded in 2007 by the NIH, a research initiative to improve understanding of human microbiota for health & disease by characterizing the human microbiome & analyze its role in human health & disease
How did the HMP go about the project?
Sequencing the genome of the human microbiota specifically in the skin, mouth, nose, digestive tract, & vagina
What is the majority of Normal flora?
Bacteria (>200)
Other names for the Normal flora?
Normal microflora, commensals, & indigenous microbiota
What does the makeup of the Normal flora depend on?
Genetics, age, sex, stress, diet, antibiotics/drugs, & environmental conditions
What are major differences between the 2 types of Normal flora, resident & transient?
Resident - Fixed, established at a given age & area, & can reestablish if disturbed. Transient - Non-pathogenic/potentially pathogenic, inhibits skin or mucous membranes for hours-weeks, doesn't produce disease, & derived from the environment
What are some reasons that Transient flora microbes are temporary?
Can be washed from external surfaces by bathing, not able to compete with resident microbes &can be killed by their substances, can't survive in acidic/alkaline conditions, & may be flushed away by bodily secretions
Examples of anatomical sites involved the Normal flora?
Skin, eyes (conjunctiva), nose (resp. tract), oral cavity, ears, genitourinary tract, & alimentary canal
What are some commensal organisms that help to breakdown/destroy debris on the skin?
Propionibacterium acne, staphylococcus epidermidis, staphylococcus aureus, diphtheroids, candida, mycobacterium smegmatis, etc.
Examples of Normal flora of the conjunctiva:
Staphylococcus epidermidis, commensol neisseria, propoinibacterium acnes, etc.
Examples of Normal flora of the oral cavity:
Streptococcus viridans, lactobacilli, staphylococcus aureus, trichomonas, etc.
Examples of Normal flora of the respiratory tract (nasal cavity):
Staphylococcus epidermidis, corynebacteria spp, staphylococcus aureus, etc.
Examples of Normal flora of the respiratory tract (nasopharynx):
Non-hemolytic streptococci, alpha-hemolytic streptococci, streptococcus pneumoniae, neisseria meningitidis, etc.
Examples of Normal flora of the respiratory tract (lower resp. tract):
Usually sterile, but can become infected from nasopharynx pathogens such as H. influenza or S. pneumoniae
What intestinal bacteria accounts for 90% of the total intestinal bacteria?
Bifidobacteria
The other 10% of bacteria in breast fed infants?
Enterobacteriaceae, enterococci, bacteroides, staphylococci, lactobacilli, & clostridia
When breast fed infants switch over to bottle feeding Bifidobacteria is followed with?
Bacteroides, enterococci, lactobacilli, clostridia, & enterics
In the esophagus & stomach what bacteria is present <10% of the time?
In the small bowel area (duodenum, jejunum, & ileum) what bacterias are present <10% of the time?
In the large bowel area what bacterias are present <10% of the time?
What are the 6 benefits of the Normal flora?
Synthesize & excrete vitamins. 2. Prevent colonization by pathogens by competing for attachment sites or essential nutrients. 3. Antagonize other bacteria through prod. of substances that kill/inhibit non-indigenous species. 4. Stim. prod. of cross-reactive antibodies. 5. Stim. development of immune system in newborns. 6. Stop/suppress entry of pathogens
What are some harmful effects of Normal flora?
The immunocompromised normal flora can overgrow = pathogenic. Dental caries, plaque, gingivitis, etc. Dental manipulation - oral streptococci can cause rheumatic fever. When substances that can be mistaken are ingested the Normal flora may cause confusion when diagnosing
What are the sterile tissues within a human?
Blood, brain, muscle, & CSF
What is an Opportunistic pathogen?
Infectious pathogen that's normally commensal but can cause disease when the host's resistance is altered. Low resistance can be caused bc of HIV, genetic factors, leukopenia, or aging
Where are Opportunistic pathogens mostly found?
Hospital settings
What can cause disturbance of the host immunity?
Administering immunosuppressants, advanced HIV, chemotherapy, damage of the skin (surgeries), or antibiotic intake disrupting the normal flora in the body
What can influence an opportunistic infection?
Impaired immunity, surgeries & instrumentation, broad spectrum antibiotic administration, or damage of an organ or system
What is an HIV patient likely to develop during the advanced stages?
Kaposi's sarcoma
Opportunistic pathogens have a high percentage of death in patients with which diseases?
AIDS & cancer patients
Which Opportunistic infections are fungus & where are they found?
Candidiasis - mouth, throat, foot, & vagina. Cryptococcosis - brain & spinal cord. Pneumocystis pneumonia - lungs.
Which Opportunistic infections are viruses & where are they found?
Cytomegalovirus - eyes, lungs, brains, & guts. PML - brain.
Which Opportunistic infections are parasites & where are they found?
Cryptosporidiosis - gut. Toxoplasmosis - brain.
Which Opportunistic infections are bacterium & where are they found?
Mycobacterium avium complex - gut, lung, & skin
Which Opportunistic infections are bacteria & where are they found?
Mycobacterium tuberculosis - lung, heart, liver, & brain
What are the differences between a True pathogen vs a Opportunistic pathogen?
True pathogens cause disease in healthy individuals & asso. with specific & reasonable diseases while opportunistic pathogens cause disease in immunocompromised & gain access/injury to sterile regions
Examples of True pathogens:
Salmonella typhi, yersinia pestis, haemophilus influenzae, bordatella pertussis, shigella dysentriae, klebsiella pneumoniae, etc.
Examples of Opportunistic pathogens:
Pseudomonas aeruginosa - candida, acinetobacter baumanii, proteus vulgaris, enterobacter, etc.
What must a pathogenic microbe do to survive a host?
Attach to host cells for colonization, evade host's innate & adaptive immune defenses to persist, obtain nutrients essential for growth to multiply, disseminate/spread within a host & other hosts (critical for species survival), & produce symptoms of disease in the host in order to be pathogenic
What are virulence factors?
Components or structure of microorganism that helps in establishment of disease or infection
How is infection established & not eliminated?
Virulence factors must overcome host's defense mechanisms
What are some virulence factors?
Attachment factors/adhesins, anti-phagocytic factors, spreading factors & enzymes, & toxins = exo/endotoxins
What is an important antiphagocytic factor for some bacteria?
Capsules
What is the host defense mechanism that prevents spreading of microorganisms?
Blood clotting
What is Leukocidin?
Pore forming cytotoxin that attacks WBCs by targeting phagocytes, NKCs, dendritic cells, & T lymphocytes
What does Leukocidin prevent?
Bacteria from phagocytosis by releasing & rupturing lysosomes. Ex: S. aureus - LukED & leukocidin AB
What is Haemolysin?
A cytotoxic protein that causes lysis of RBCs by disturbing cell membrane & liberates hemoglobin
What is Alpha hemolytic streptococci?
Secretes hemolysins that cause the incomplete lysis of RBCs
What is Beta hemolytic streptococci?
Secretes hemolysins that cause the complete lysis of RBCs
What does the Fibrin coat do?
Protect the bacterium from phagocytosis & isolate it from other defenses of the host. Makes bacteria more virulent
How are Hyaluronidase's important in regards to drugs?
Mixed with the drug to help spread the drug throughout a body tissue
What is the difference between host Collagenases & bacterial Collagenases?
Host collagenases destroy extracellular structures in the pathogenesis of bacteria. Bacterial collagenases allow bacteria to breakdown protein to invade the host.
Collagenases are association with what disease?
Clostridium perfrinogens - gas gangrene
In the Infection process what does bacteria do?
Bacteria invade the tissues, grow, & reproduce
In the Intoxication process what does bacteria do?
Bacteria produce certain potent effective toxins which cause disease & symptoms of disease
What is Toxemia?
State caused by toxins entering the bloodstream of the host
What are the Endotoxins?
Lipopolysaccharides (LPS)
What are the Exotoxins?
AB toxins, specific host site exotoxins, membrane disrupting exotoxins, & super antigen
What are some significant features of Exotoxins?
Some gram pos & neg, protein location = secreted from cell & gene location = plasmid or bacteriophage, high toxicity, highly antigenic (antitoxins), vaccine from toxoids, & heat labile
Examples of Exotoxins:
Toxins prod. by S. aureus, bacillus cereus, streptococcus pyogenes, b. anthracis, & c. tetani
What are some significant features of Endotoxins?
Most gram neg & listeria, protein location = part of cell/LPS that fragments off & gene location = bacterial chromosomes, low toxicity, poorly antigenic, no vaccine, & heat stable
Examples of Endotoxins:
Gram neg pathogens such as Escherichia coli, salmonella, shigella, pseudomonas, & neisseria
What is the exotoxin AB toxin?
B portion binds to the receptors & A portion can cause toxicity
What is the exotoxin Specific host site exotoxin?
Type of AB toxin that affects the specific regions of the host such as neurotoxins affects CNS, enterotoxins affects intestines, & general cells or tissues are affected by cytotoxins
What is the exotoxin Membrane disrupting toxin?
Type of AB toxin, but they act together by disrupting host cell membranes e.g., hemolysis, phospholipases
What is the exotoxin Superantigen?
Unusual bacterial toxins that triggers T cells (T4 Lymphocytes) to release cytokines - bind to surface of target cell but don't enter
How do AB toxins enter the cell?
B subunit binds to the target cell & allows A subunit to enter the cell
What occurs once Conventional antigens are engulfed by APCs?
They're degraded into epitopes, bind to peptide groove of MHC-II molecules, & are put on surface of the APC
When Superantigens bind outside MHC-II & activate T4-Lymphocytes what is the result?
Secretion of excessive amounts of IL-2 & activation of self-reactive T-Lymphocytes
Increased IL-2 in the blood can cause what?
Fever, nausea, vomitting, diarrhea, & malaise. Excess stim. leads to prod. of inflammatory cytokines like TNF-alpha, IL-1, inflammatory chemokines like IL-8, & platelet-activating factor (PAF) = shock & multiple organ system failure
Examples of bacterial Superantigens:
Staphylococcal enterotoxins - food poisoning. Staphylococcal toxic shock toxin (TSST-1) - toxic shock syndrome. Staphylococcal exfoliating toxins - scalded skin syndrome. Staphylococcal pyrogenic exotoxins (exotoxin A & B) - shock.
What is Toxic shock syndrome (TSST)?
Toxins produced by Staphylococcal aureus. Asso. with cuts or burns on skin, recent surgery, using contraceptive sponges, diaphragms, tampons/menstrual cups, or a viral infection like the flu or chickenpox
Symptoms & complications of TSST:
High fever, vomiting or diarrhea, redness around eyes & vagina, sunburn rash, low bp, headache, & muscle pain. Complications = shock, renal failure, or death
Difference between Reinfection & superinfection:
Reinfection is infection by the same organism in a host after recovery while superinfection is before recovery
What is a Focal infection?
Infection at localized site prod. general effects
What is a Nosocomial infection?
Infections acquired within a hospital
What is an Iatrogenic infection?
State of health or adverse effect caused by medical treatment
What are the differences between Exogenous infections & endogenous infections?
Exo infections are pathogens enter the body from outside environment via contaminated device, healthcare worker, surface, or other vector. Endo infections are pathogens present on/in host itself without prior symptoms
Examples of Exogenous infections:
Dysentery, cholera, influenza, & covid-19
Examples of Endogenous infections:
Periodontal diseases, aspiration pneumonitis, & bacterial vaginosis