1. Bacteria - Microbiology (USMLE).docx

**Structure** **Chemical Composition** **Function** **Appendages** **- Flagellum** \- Protein \- Motility **- Pilus\ - Fimbria** \- Glycoprotein \- Mediate adherence of bacteria to cell surface **Specialized Structures** **- Spore** \- Keratinlike coat\ - Dipicolinic acid\ - Peptidoglyca...

**Structure** **Chemical Composition** **Function** **Appendages** **- Flagellum** \- Protein \- Motility **- Pilus\ - Fimbria** \- Glycoprotein \- Mediate adherence of bacteria to cell surface **Specialized Structures** **- Spore** \- Keratinlike coat\ - Dipicolinic acid\ - Peptidoglycan\ - DNA **[Gram positive only]**\ [Survival]\ - Resist dehydration\ - Resists Chemical\ - Resists Heat **Cell Envelope** **Bacteria Capsule** \- Discrete layer usually made of polysaccharides (and rarely proteins) \- Protects against phagocytosis **Slime (S) layer** \- Loose network of polysaccharides \- Mediates adherence to surfaces,\ - Plays a role in biofilm formation (eg, indwelling catheters) **Outer membrane** **[Outer leaflet:]**\ - Contains endotoxin (LPS/LOS) **[Embedded proteins:]**\ - Porins\ - Other outer membrane proteins (OMPs) **[Inner leaflet:]**\ - Phospholipids **[Gram negative only]** [Endotoxin:]\ - Lipid A induces TNF and IL-1\ - Antigenic O polysaccharide component [Embedded proteins:]\ - Most OMPs are antigenic [Porins:]\ - Transport across outer membrane **Periplasm** \- Space between cytoplasmic membrane and outer membrane in gram ⊝ bacteria (peptidoglycan in middle) \- Accumulates components exiting gram ⊝ cells\ - Including hydrolytic enzymes (eg, β-lactamases **Cell wall** \- Peptidoglycan is a sugar backbone with peptide side chains cross-linked by transpeptidase \- Netlike structure gives rigid support\ - Protects against osmotic pressure damage **Cytoplasmic membrane** **[Phospholipid Bilayer Sac]**\ - Embedded proteins (eg, penicillin-binding proteins \[PBPs\]) and other enzymes **[Lipoteichoic acids (gram positive)]**\ - Only extend from membrane to exterior \- Site of oxidative and transport enzymes\ - Penicillin-binding proteins involved in cell wall synthesis\ **[Lipoteichoic acids (gram positive)]**\ - Lipoteichoic acids induce TNF-α and IL-1 +-----------------------+-----------------------+-----------------------+ | **Stains** | | | +=======================+=======================+=======================+ | **Gram Stain** | \- First-line lab | **[Bacteria which | | | test in bacterial | cannot be | | | identification.\ | visualized]{.underlin | | | [**Peptidoglycan | e}**\ | | | Layer\ | **[1. Too | | | **Crystal violet Dye\ | thin]**\ | | | ]- | - Treponema\ | | | Bacteria with thick | - Leptospira | | | peptidoglycan layer | | | | retain crystal violet | **[2. High lipid | | | dye (gram ⊕)\ | content]* | | | [Red or Pink | *\ | | | Dye]\ | - Mycobacteria\ | | | - Bacteria with thin | **[3. No cell | | | peptidoglycan layer | wall]**\ | | | turn red or pink | - Mycoplasma,\ | | | (gram ⊝) with | - Ureaplasma\ | | | counterstain. | **[4. Intracellular | | | | Bacteria] | | | | **\ | | | | - Legionella\ | | | | - Rickettsia\ | | | | - Chlamydia\ | | | | - Bartonella\ | | | | - Anaplasma\ | | | | - Ehrlichia | +-----------------------+-----------------------+-----------------------+ | **Giemsa Stain** | \- Helicobacter | | | | pylori\ | | | | - Trypanosomes A\ | | | | - Plasmodium\ | | | | - Chlamydia\ | | | | - Rickettsia\ | | | | - Borrelia | | +-----------------------+-----------------------+-----------------------+ | **Periodic | **[Targets]{.underlin | | | Acid-Schiff Stain** | e}**\ | | | | - | | | | Mucopolysaccharides\ | | | | - Glycogen\ | | | | **[Clinical]{.underli | | | | ne}**\ | | | | - Used to diagnose | | | | Whipple disease | | | | (Tropheryma whipplei) | | +-----------------------+-----------------------+-----------------------+ | **Ziel-Neelsen Stain | **[Acid-fast | **[Auramine-Rhodamine | | (Carbol Fuchsin)** | bacteria] | Stain]**\ | | | **\ | - More often used for | | | - Nocardia (stains | screening | | | mycolic acid in cell | (inexpensive, more | | | wall)\ | sensitive) | | | - Protozoa (eg, | | | | Cryptosporidium | | | | oocysts)\ | | | | - Mycobacteria | | +-----------------------+-----------------------+-----------------------+ | **Indie Ink Stain** | **[Mucicarmine | | | | Staining] | | | | **\ | | | | [Used to stain thick | | | | polysaccharide | | | | capsule | | | | red]\ | | | | - Cryptococcus | | | | neoformans | | +-----------------------+-----------------------+-----------------------+ | **Silver Stain** | **[Absorb Silver | works by depositing | | | Ions]**\ | silver salts on | | | - Fungi (eg, | microbial cell walls, | | | Coccidioides, | making them visible | | | Pneumocystis | under a light | | | jirovecii, | microscope | | | Aspergillus | | | | fumigatus)\ | | | | - Bartonella | | | | Henselae\ | | | | - Helicobacter | | | | Pylori\ | | | | - Legionella | | +-----------------------+-----------------------+-----------------------+ | **Fluorescent | **[Intracellular | | | Antibody Stain** | Microorganisms]{.unde | | | | rline}**\ | | | | - Pneumocystis | | | | jirovecii\ | | | | - Cryptosporidium\ | | | | - Bacteria\ | | | | - Viruses\ | | | | - Giardia | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | **Aerobic Bacteria** | \- Need oxygen to | | | | survive.\ | | | | - Oxygen is used in | | | | their energy | | | | production | | +-----------------------+-----------------------+-----------------------+ | **Anaerobic | \- These bacteria do | **[Gastrointestinal | | Bacteria** | not require oxygen | Tract]**\ | | | and may even be | - Anaerobes are | | | harmed by it.\ | normal microbiota in | | | - They rely on | GI tract\ | | | fermentation or | - Typically | | | anaerobic | pathogenic | | | respiration\ | elsewhere.\ | | | **[Vulnerability]{.un | **[Aminoglycosides]{. | | | derline}**\ | underline}**\ | | | - Lack catalase | - Ineffective against | | | and/or superoxide | anaerobes because | | | dismutase\ | these antibiotics | | | - Susceptible to | require O2 to enter | | | oxidative damage.\ | into bacterial cell. | | | **[Difficulty]{.under | | | | line}**\ | | | | - Generally foul | | | | smelling (short-chain | | | | fatty acids)\ | | | | - Difficult to | | | | culture\ | | | | - Produce gas in | | | | tissue (CO2 and H2). | | +-----------------------+-----------------------+-----------------------+ | **Facultative | \- These bacteria can | \- Streptococci\ | | Anaerobes** | grow with or without | - Staphylococci\ | | | oxygen.\ | - Enteric | | | - They use oxygen | gram-negative | | | when it is available | bacteria. | | | but can also switch | | | | to fermentation or | | | | anaerobic respiration | | | | if it is absent.\ | | | | - May use O2 as a | | | | terminal electron | | | | acceptor to generate | | | | ATP but can also use | | | | fermentation and | | | | other O2-independent | | | | pathways. | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | **Obligate | \- These bacteria | **[Rely on host | | Intracellular | **must** live and | ATP]**\ | | Bacteria** | replicate inside the | - Rickettsia,\ | | | host cell as they | - Chlamydia,\ | | | rely on the host\'s | - Coxiella | | | cellular machinery | | | | for survival and | | | | reproduction.\ | | | | - They are unable to | | | | grow outside of host | | | | cells because they | | | | lack the necessary | | | | metabolic pathways or | | | | enzymes for | | | | independent survival. | | +-----------------------+-----------------------+-----------------------+ | **Facultative | \- These bacteria are | \- Salmonella\ | | Intracellular | capable of living | - Neisseria\ | | Bacteria** | both **inside and | - Brucella\ | | | outside host | - Mycobacterium\ | | | cells**.\ | - Listeria\ | | | - They can replicate | - Francisella\ | | | and survive outside | - Legionella\ | | | of host cells in the | - Yersinia pestis | | | environment\ | | | | - They are also able | | | | to enter cells, | | | | especially immune | | | | cells like | | | | macrophages, to avoid | | | | the immune system and | | | | potentially cause | | | | chronic infections. | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | **Encapsulated | \- Capsule is | \- Streptococcus | | Bacteria** | composed mainly of | pneumoniae\ | | | polysaccharides\ | - Haemophilus | | | - Although some | influenzae type b,\ | | | bacteria may have | - Neisseria | | | capsules made from | meningitidis,\ | | | other substances like | - Escherichia coli,\ | | | polypeptides.\ | - Salmonella,\ | | | - Conjugate can serve | - Klebsiella | | | as an antigen in | pneumoniae\ | | | vaccines.\ | - Group B Strep.\ | | | **[T-Cell Independent | - Their capsules | | | Antigens] | serve as an | | | **\ | antiphagocytic | | | - Polysaccharides are | virulence factor. | | | T-cell independent | | | | antigens\ | | | | - This means they can | | | | stimulate B cells to | | | | produce antibodies, | | | | but they do not | | | | typically involve | | | | T-helper cells in the | | | | immune response.\ | | | | **[Protein Conjugated | | | | Enhanced | | | | Immunogenicity]{.unde | | | | rline}**\ | | | | - When a capsular | | | | polysaccharide is | | | | conjugated | | | | (chemically linked) | | | | to a protein carrier, | | | | the protein acts as a | | | | T-cell dependent | | | | antigen.\ | | | | - This allows for the | | | | activation of both B | | | | cells and T-helper | | | | cells, leading to a | | | | much stronger and | | | | longer-lasting immune | | | | response. | | +-----------------------+-----------------------+-----------------------+ | **Urease-Positive | **[Urease Function\ | \- Proteus,\ | | Organisms** | ]**- | - Cryptococcus,\ | | | Urease hydrolyzes | - H pylori,\ | | | urea to release | - Ureaplasma,\ | | | ammonia and CO2 leads | - Nocardia,\ | | | to increased pH.\ | - Klebsiella,\ | | | - Predisposes to | - S epidermidis,\ | | | struvite (magnesium | - S saprophyticus. | | | ammonium phosphate) | | | | stones, particularly | | | | Proteus. | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | **Catalase-Positive | **[Catalase | **[Catalase Positive | | Organisms** | Function] | Bacteria] | | | **\ | **\ | | | - Catalase degrades | - Bordetella | | | H2O2 into H2O and | pertussis,\ | | | bubbles of oxygen\ | - Helicobacter | | | - Before it can be | pylori,\ | | | converted to | - Burkholderia | | | microbicidal products | cepacia,\ | | | by the enzyme | - Nocardia,\ | | | myeloperoxidase.\ | - Pseudomonas,\ | | | **[Chronic | - Listeria,\ | | | Granulomatous | - Aspergillus,\ | | | Disease]* | - Candida,\ | | | *\ | - E coli,\ | | | - People with chronic | - Serratia,\ | | | granulomatous disease | - Staphylococci. | | | (NADPH oxidase | | | | deficiency) have | | | | recurrent infections | | | | with certain catalase | | | | ⊕ organisms. | | +-----------------------+-----------------------+-----------------------+ | **Pigment-producing | **[Actinomyces | \- Actinomyces | | Bacteria** | Israelii] | israelii\ | | | **\ | - Staphylococcus | | | - Yellow "sulfur" | aureus\ | | | granules, which are | - Pseudomonas | | | composed of filaments | aeruginosa\ | | | of bacteria\ | - Serratia marcescens | | | **[Staphylococcus | | | | Aureus]\ | | | | **-Golden yellow | | | | pigment\ | | | | **[Pseudomonas | | | | Aeruginosa\ | | | | ]**- | | | | Blue-green pigment | | | | (pyocyanin and | | | | pyoverdin)\ | | | | **[Serratia | | | | Marcescens]{.underlin | | | | e}**\ | | | | - Red pigment | | +-----------------------+-----------------------+-----------------------+ | **In Vivo Biofilm | **[Staphylococcus | \- Staphylococcus | | Producing Bacteria** | Epidermidis]{.underli | Epidermidis\ | | | ne}**\ | - Streptococci | | | - Catheter and | Viridans (S mutans, S | | | prosthetic device | sanguinis)\ | | | infections\ | - Pseudomonas | | | **[Streptococci | Aeruginosa\ | | | Viridans (S mutans, S | - Hemophilus | | | sanguinis)]{.underlin | influenzae | | | e}**\ | | | | - Dental plaques\ | | | | - Infective | | | | endocarditis\ | | | | **[Pseudomonas | | | | Aeruginosa]{.underlin | | | | e}**\ | | | | - Respiratory tree | | | | colonization in | | | | patients with cystic | | | | fibrosis\ | | | | - | | | | Ventilator-associated | | | | pneumonia | | | | | | | | \- Contact | | | | lens--associated | | | | keratitis\ | | | | [**Nontypeable | | | | (unencapsulated) H | | | | influenzae**\ | | | | ]- Otitis | | | | media | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | **Spore-Forming | **[Spores in Gram ⊕ | \- Bacillus B | | Bacteria** | Bacteria] | anthracis (anthrax),\ | | | **\ | - Bacillus cereus | | | - Form spores when | (food poisoning),\ | | | nutrients are | - Clostridium | | | limited.\ | Botulinum | | | - Spores lack | (botulism),\ | | | metabolic activity | - Clostridium | | | and are highly | Difficile | | | resistant to heat and | (pseudomembranous | | | chemicals.\ | colitis),\ | | | - Core contains | - | | | dipicolinic acid | Clostridium Perfringe | | | (responsible for heat | ns | | | resistance). | (gas gangrene),\ | | | | - Clostridium Tetani | | | \- Must autoclave to | (tetanus).\ | | | kill spores (as is | - Autoclave to kill | | | done to surgical | Bacillus and | | | equipment) by | Clostridium (ABC). | | | steaming at 121°C for | | | | 15 minutes.\ | | | | - Hydrogen peroxide | | | | and iodine-based | | | | agents are also | | | | sporicidal. | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | **Bacterial Virulence | | | | Factors** | | | +-----------------------+-----------------------+-----------------------+ | **Capsule | \- Highly charged\ | | | Polysaccharide** | - Hydrophilic | | | | structure.\ | | | | **[Function]{.underli | | | | ne}**\ | | | | - Acts as barrier to | | | | phagocytosis and | | | | complement-mediated | | | | lysis.\ | | | | - Major determinant | | | | of virulence | | +-----------------------+-----------------------+-----------------------+ | **Protein A** | \- Binds Fc region of | **[Expressed | | | IgG.\ | by]**\ | | | **[Function]{.underli | - S aureus | | | ne}**\ | | | | - Prevents | | | | opsonization and | | | | phagocytosis. | | +-----------------------+-----------------------+-----------------------+ | **IgA Protease** | \- Enzyme that | **[Secreted | | | cleaves IgA, allowing | by]**\ | | | bacteria to adhere to | - S pneumoniae,\ | | | and colonize mucous | - H influenzae type | | | membranes. | b\ | | | | - Neisseria | +-----------------------+-----------------------+-----------------------+ | **M Protein** | **[Function]{.underli | **[Expressed | | | ne}**\ | by]**\ | | | - Helps prevent | - Group A | | | phagocytosis.\ | streptococci | | | - Sequence homology | | | | with human cardiac | | | | myosin (molecular | | | | mimicry)\ | | | | - Possibly underlies | | | | the autoimmune | | | | response seen in | | | | acute rheumatic fever | | +-----------------------+-----------------------+-----------------------+ -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Bacterial Genetics** ------------------------ ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ----------------------- **Transformation** \- Transformation is the process where competent bacteria uptake free, naked DNA fragments from the environment, often from lysed bacterial cells.\  - This DNA can integrate into the bacterial chromosome, leading to genetic variation.\ - Competent bacteria can bind and import short pieces of environmental naked bacterial chromosomal DNA (from bacterial cell lysis).\ - The transfer and expression of newly transferred genes is called transformation.\ **[Examples]**\ - S pneumoniae,\ - H influenzae type b\ - Neisseria\ **[Inhibition]**\ - Adding deoxyribonuclease degrades naked DNA, preventing transformation **Coagulation** **[\  ]-** Coagulation (specifically F+ and Hfr conjugation) refers to the transfer of genetic material, particularly plasmids, between two bacteria through direct contact via a pilus (a mating bridge).\ - In F+ conjugation, a plasmid is transferred, while in Hfr conjugation, chromosomal genes can also be integrated.\ **[\ F^+^ X F^-^ Conjugation\ ]**- F+ plasmid contains genes required for sex pilus and conjugation.\ - Bacteria without this plasmid are termed F--\ - Sex pilus on F+ bacterium contacts F− bacterium.\ - A single strand of plasmid DNA is transferred only, across the conjugal bridge ("mating bridge").\ - No transfer of chromosomal DNA.**[\ Hfr x F^-^ Conjugation\ ]**- F+ plasmid can become incorporated into bacterial chromosomal DNA, termed high frequency recombination (Hfr) cell.\ - Transfer of leading part of plasmid\ - Transfer of chromosomal DNA also.\ - High-frequency recombination may integrate some of those bacterial genes.\ - Recipient cell remains F-- but now may have new bacterial genes. **Transduction** **[-]** Transduction is the process by which bacterial DNA is transferred from one bacterium to another by a bacteriophage (a virus that infects bacteria).\  - This can be generalized (any part of the bacterial genome is transferred) or specialized (specific bacterial genes are transferred along with viral DNA).**[\ \ 1) Generalized Transduction]**\ - A "packaging" error.\ [Lytic phage]\ - Infects bacterium, leading to cleavage of bacterial DNA.\ - Parts of bacterial chromosomal DNA may become packaged in capsid of lytic phage.\ - Phage infects another bacterium, transferring these genes.\ **[2) Specialized Transduction]**\ - An "excision" event.\ [Lysogenic phage]\ - Infects bacterium; viral DNA incorporates into bacterial chromosome.\ - When phage DNA is excised, flanking bacterial genes may be excised with it.\ - DNA is packaged into phage capsid and can infect another bacterium.\ **[Encoded Gene for Bacterial Toxins]**\ - Group A strep erythrogenic toxin\ - Botulinum toxin\ - Cholera toxin\ - Diphtheria toxin\ - Shiga toxin. **Transposition** \- Transposition refers to the \"jumping\" of transposons (mobile genetic elements) within the bacterial genome or between a plasmid and chromosome.\ - Transposons can move independently and integrate into new genetic locations, often causing mutations or gene regulation changes.\ - A "jumping" process involving a transposon (specialized segment of DNA), which can copy and excise itself and then insert into the same DNA molecule or an unrelated DNA (eg, plasmid or chromosome).\ - Critical in creating plasmids with multiple drug resistance and transfer across species lines\ - For example, Tn1546 with vanA from Enterococcus to S aureus -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Main features of exotoxins and endotoxins** ----------------------------------------------- ------------------------------------------------------------------ -------------------------------------------------------------------------------- **Exotoxins** **Endotoxins** **Source** \- Certain species of gram ⊕ and gram ⊝ bacteria \- Outer cell membrane of most gram ⊝ bacteria **Secreted from cell** \- Yes \- No **Chemistry** \- Polypeptide \- Lipid A component of LPS (structural part of bacteria; released when lysed) **Location of Genes** \- Plasmid or bacteriophage \- Bacterial chromosome **Toxicity** \- High (fatal dose on the order of 1 µg) \- Low (fatal dose on the order of hundreds of micrograms **Clinical Effects** \- Various effects (see following pages) \- Fever\ - Shock (hypotension),\ - DIC **Mode of Action** \- Various effects (see following pages) \- Induces TNF, IL-1, and IL-6 **Antigenicity** **[Antitoxins]**\ \- Poorly antigenic - Induces high-titer antibodies called antitoxins **Vaccines** **[Vaccine Available]**\ **[No Vaccine Available]**\ - Toxoids used as vaccines - No toxoids formed and no vaccine available **Heat Stability** \- Destroyed rapidly at 60°C\ \- Stable at 100°C for 1 hr - Except staphylococcal enterotoxin and E coli heat stable toxin **Typical Diseases** \- Diphtheria\ \- Meningococcemia;\ - Tetanus\ - Sepsis (by gram ⊝ rods) - Botulism\ - Cholera  --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Bacteria with Exotoxins** ------------------------------------------ ------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------ **Bacteria** **Toxin** **Mechanism** **Manifestation** **Inhibits Protein Synthesis** **Corynebacterium Diphtheriae** Diphtheria toxin **[Inactivate Elongation Factor (EF-2)]**\ \- Pharyngitis with pseudomembranes in throat\ [ADP-ribosylation]\ - Severe lymphadenopathy (bull neck)\ - Toxin induces ADP-ribosylation of EF-2 inactivates it, blocking its function in the elongation phase of protein synthesis. - Myocarditis **Pseudomonas Aeruginosa** Exotoxin Aa \- Host cell death **Shigella spp** Shiga toxin **[Inactivates 60S Ribosome]**\ \- Damages GI mucosa resulting in dysentery\ - Through removal adenine from rRNA - Enhances cytokine release leads to hemolytic-uremic syndrome (HUS; prototypically in EHEC serotype O157:H7)\ - Unlike Shigella, EHEC does not invade host cells **Enterohemorrhagic (E coli)** **Increases Fluid Secretion** **Enterotoxigenic (E coli)** \- Heat-Labile Toxin (LT)\ **[Overactivates Adenylate Cyclase (increasing cAMP)]**\ **[Bacteria which increase cAMP]**\ \ - Leads to increased Cl− secretion in gut and H2O efflux\ -\ \ \ **[Bacteria which increase cGMP]**\ - Heat-Stable Toxin (ST) **[Overactivates Guanylate Cyclase (increased cGMP)]**\ - Cholera\ - Leads to decreased resorption of NaCl and H2O in gut - Anthracis\ - Pertussis\ - E coli **Bacillus Anthracis** \- Anthrax toxin **[Mimics Adenylate Cyclase (increasing cAMP)]**\ **[Presentation]**\ - The elevated cAMP levels interfere with normal cellular signalling, disrupt water and ion transport, and impair immune response - Edematous borders of black eschar in cutaneous anthrax **Vibrio Cholerae** \- Cholera toxin **[Overactivates Adenylate Cyclase (increasing cAMP)]**\ \- Voluminous "rice-water" diarrhea - By permanently activating Gs **Increases Phagocytic Ability** **Bordetella Pertussis** \- Pertussis Toxin **[Activates Adenylate Cyclase (increasing cAMP)]**\ **[Whooping cough]**\ - By inactivating inhibitory subunit (Gi) - Child coughs on expiration and "whoops" on inspiration; can cause "100-day cough" in adults;\ - Associated with posttussive emesis **Inhibit Release of Neurotransmitters** **Clostridium Tetani** \- Tetanospasmin **[Cleave SNARE (soluble NSF attachment protein receptor),\ \- Toxin prevents release of inhibitory (GABA and glycine) neurotransmitters from Renshaw cells in spinal cord.\ ]**- Cleaves a set of proteins required for neurotransmitter release via vesicular fusion **[Presentation]**\ - Spastic paralysis\ - Risus sardonicus\ - Trismus (lockjaw)\ - Opisthotonos **Clostridium Botulinum** \- Botulinum Toxin \- Infant botulism---caused by ingestion of spores (eg, from soil, raw honey).\ - Toxin produced in vivo Foodborne botulism---caused by ingestion **Lyse Cell Membranes** **Clostridium Perfringens** \- Alpha Toxin **[Phospholipase (lecithinase)]**\ **[Degradation of Phospholipids]**\ - Degrades tissue and cell membranes - Leading to myonecrosis ("gas gangrene")\ - Leads to hemolysis ("double zone" of hemolysis on blood agar) **Streptococcus Pyogenes** \- Streptolysin O **[Protein Cell Membrane Degradation]**\ \- Host antibodies against toxin (ASO) used to diagnose rheumatic fever\ - Forms pores in the membranes of host cells.\ - Do not confuse with immune complexes of poststreptococcal glomerulonephritis) - Lyses RBCs; contributes to β-hemolysis **Superantigens Causing Shock** **Staphylococcus Aureus** \- Toxic shock syndrome toxin (TSST-1)\ \- Cross-links β region of TCR to MHC class II on APCs outside of the antigen binding site.\ **[Toxic shock syndrome:\ - Exfoliative toxin\ **[Cytokine Release Resulting in shock]**\ ]**- Fever\ - Enterotoxin - IL-1,\ - Rash\ - IL-2,\ - Shock\ - IFN-γ\ - Other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (heat-stable enterotoxin) - TNF-α **Streptococcus Pyogenes** \- Erythrogenic exotoxin A **[Toxic shock--like syndrome:]**\ - Fever\ - Rash\ - Shock\ - Scarlet fever **Bacteria with Endotoxin** **Bacteria** **Manifestation** \- Lipopolysaccharide (LPS) found in outer membrane of gram-negative bacteria (both cocci and rods).\ **[Virulent Factors of LPS]**\ - O-antigen\ - Core polysaccharide\ - Lipid A (most toxic)\ - Neisseria have lipo-oligosaccharide.\ **[Pathophysiology]**\ - Released upon cell lysis or by living cells by blebs detaching from outer surface membrane (vs exotoxin, which is actively secreted).\ **[Main effects:]**\ 1. Macrophage activation (TLR4/CD14)\ 2. Complement activation\ 3. Tissue factor activation. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Hemolytic Bacteria**  ------------------------------ ------------------------------------------------------------------------------------------------------------------------ ---------------------------------------------- -- **Mechanism** **Examples** **Alpha Hemolytic Bacteria** \- Partial oxidation of hemoglobin leading to greenish or brownish colour without clearing around growth on blood agar \- Streptococcus pneumoniae\ - Viridans streptococci. **Beta Hemolytic Bacteria** \- Complete lysis of RBCs leading to pale/clear area surrounding colony on blood agar \- Staphylococcus aureus,\ - Streptococcus pyogenes (group A strep),\ - Streptococcus agalactiae (group B strep),\ - Listeria monocytogenes. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- +-----------------------+-----------------------+-----------------------+ | **Special culture | | | | requirements** | | | +=======================+=======================+=======================+ | **Bug** | **Media used for | **Media Content/ | | | Isolation** | Other** | +-----------------------+-----------------------+-----------------------+ | **- Haemophilus | \- Chocolate agar | **[Media | | influenzae** | | Content]* | | | | *\ | | | | - Factors V (NAD+ )\ | | | | - Factor X (hematin) | +-----------------------+-----------------------+-----------------------+ | **- Neisseria | \- Thayer-Martin agar | [**Media Content**\ | | gonorrhoeae\ | | Vancomycin]{.underlin | | - Neisseria | | e}\ | | meningitidis** | | - Selectively favors | | | | growth of Neisseria\ | | | | - By inhibiting | | | | growth of gram ⊕ | | | | organisms\ | | | | [Trimethoprim and | | | | Colistin] | | | | \ | | | | - Selectively favours | | | | Neisseria\ | | | | - By inhibiting | | | | growth of gram ⊝ | | | | organisms except | | | | Neisseria\ | | | | [Nystatin]{.underline | | | | }\ | | | | - Prevents growth of | | | | fungi | +-----------------------+-----------------------+-----------------------+ | **- Bordetella | \- Bordet-Gengou agar | **[Media | | pertussis** | | Content]* | | | -Regan-Lowe medium | *\ | | | | - Potato extract\ | | | | - Charcoal, blood, | | | | and antibiotic | +-----------------------+-----------------------+-----------------------+ | **- Corynebacterium | \- Tellurite agar\ | | | diphtheriae** | - Löffler medium | | +-----------------------+-----------------------+-----------------------+ | **- Mycobacterium | \- Löwenstein-Jensen | | | tuberculosis** | medium,\ | | | | - Middlebrook medium\ | | | | - Rapid automated | | | | broth cultures | | +-----------------------+-----------------------+-----------------------+ | **- Mycoplasma | \- Eaton agar | **[Media | | pneumoniae** | | Content]* | | | | *\ | | | | - Requires | | | | cholesterol | +-----------------------+-----------------------+-----------------------+ | **- | \- MacConkey agar | **[Media | | Lactose-fermenting | | Content]* | | Enterics** | | *\ | | | | - Fermentation | | | | produces acid\ | | | | - Causing colonies to | | | | turn pink | +-----------------------+-----------------------+-----------------------+ | **- E coli** | \- Eosin--methylene | **[Media | | | blue (EMB) agar | Content]* | | | | *\ | | | | - Colonies with green | | | | metallic sheen | +-----------------------+-----------------------+-----------------------+ | **- Brucella\ | \- Charcoal yeast | \- | | - Francisella\ | extract agar buffered | | | - Legionella\ | with cysteine and | | | - Pasteurella** | iron | | +-----------------------+-----------------------+-----------------------+ | **- Fungi** | \- Sabouraud agar | | +-----------------------+-----------------------+-----------------------+ +-----------------+-----------------+-----------------+-----------------+ | **Staphylococcu | **[Virulence | \- Gram ⊕\ | **[Toxic Shock | | s | Factor]{.underl | - β-hemolytic\ | Syndrome | | aureus** | ine}**\ | **[Enzymes]{.un | (TSST-1)]{.unde | | | - Binds Fc-IgG, | derline}**\ | rline}\ | | | inhibiting | - Catalase ⊕\ | **- TSST-1 is a | | | complement | - Coagulase ⊕\ | superantigen | | | activation and | - Urease ⊝\ | that binds to | | | phagocytosis.\ | **[Shape]{.unde | MHC II and | | | **[Locations]{. | rline}**\ | T-cell | | | underline}**\ | - Cocci in | receptor\ | | | - Snare\ | clusters\ | - This results | | | - Ears\ | **[Virulence | in polyclonal | | | - Axilla\ | Factor]{.underl | T-cell | | | - Groin\ | ine}**\ | activation and | | | **[Causes]{.und | - Protein A\ | cytokine | | | erline}**\ | - Ferments | release.\ | | | - Inflammatory | mannitol | [Staphylococcal | | | disease---skin | | toxic shock | | | infections\ | | syndrome | | | - Organ | | (TSS)]{.underli | | | abscesses\ | | ne}\ | | | - Pneumonia | | **[Presentation | | | (often after | | ]** | | | influenza virus | | \ | | | infection)\ | | - Fever\ | | | - Infective | | - Vomiting\ | | | endocarditis\ | | - Diarrhea\ | | | - Septic | | - Rash\ | | | arthritis\ | | - Desquamation\ | | | - | | - Shock\ | | | Osteomyelitis.\ | | - End-organ | | | - | | failure.\ | | | Toxin-mediated | | [Laboratory]{.u | | | disease---toxic | | nderline}\ | | | shock syndrome | | - | | | (TSST-1)\ | | Increased AST\ | | | - Scalded skin | | - Increased | | | syndrome | | ALT\ | | | (exfoliative | | - Increased | | | toxin)\ | | bilirubin. | | | - Rapid-onset | | | | | food poisoning | | [Risk | | | (enterotoxins). | | Factors]{.under | | | \ | | line}\ | | | **[MRSA | | - Associated | | | (methicillin-re | | with prolonged | | | sistant | | use of vaginal | | | S | | tampons or | | | aureus)]{.under | | nasal packing.\ | | | line}**\ | | - Compare with | | | - Important | | Streptococcus | | | cause of | | pyogenes TSS (a | | | serious | | toxic | | | healthcare | | shock--like | | | associated and | | syndrome | | | community-acqui | | associated with | | | red | | painful skin | | | infections.\ | | infection).\ | | | [MecA | | **[Food | | | Gene]{.underlin | | Poisoning]{.und | | | e}\ | | erline}**\ | | | - Provides | | - S aureus food | | | resistance due | | poisoning due | | | to altered | | to ingestion of | | | penicillinbindi | | preformed toxin | | | ng | | resulting in | | | proteins\ | | short | | | [Panton-Valenti | | incubation | | | ne | | period (2--6 | | | Leukocidin | | hr) followed by | | | (PVL)]{.underli | | non-bloody | | | ne}\ | | diarrhea and | | | - Kills | | emesis.\ | | | leukocytes and | | - Enterotoxin | | | causes tissue | | is heat stable | | | necrosis. | | is not | | | | | destroyed by | | | | | cooking.\ | | | | | **[Coagulase]{. | | | | | underline}**\ | | | | | - Forms fibrin | | | | | clot around | | | | | itself | | | | | resulting | | | | | abscess. | +-----------------+-----------------+-----------------+-----------------+ | **Staphylococcu | \- Infects | \- Gram ⊕\ | | | s | prosthetic | **[Enzymes]{.un | | | epidermidis** | devices (eg, | derline}**\ | | | | hip implant, | - Catalase ⊕\ | | | | heart valve)\ | - Coagulase ⊝\ | | | | - IV catheters | - Urease ⊕\ | | | | by producing | **[Shape]{.unde | | | | adherent | rline}**\ | | | | biofilms. | - Cocci in | | | | | clusters\ | | | | | **[Other]{.unde | | | | | rline}**\ | | | | | - Novobiocin | | | | | sensitive.\ | | | | | - Does not | | | | | ferment | | | | | mannitol (vs S | | | | | aureus) | | +-----------------+-----------------+-----------------+-----------------+ | **Staphylococcu | \- Normally | \- Gram ⊕\ | | | s | colonises | **[Enzymes]{.un | | | Saprophyticus** | female genital | derline}**\ | | | | tract\ | - Catalase ⊕\ | | | | **[Presentation | - Coagulase ⊝\ | | | | ]** | - Urease ⊕\ | | | | \ | **[Shape]{.unde | | | | [Urinary tract | rline}**\ | | | | infection | - Cocci in | | | | (UTI)]{.underli | clusters.\ | | | | ne}\ | **[Other]{.unde | | | | - 2^nd^ most | rline}**\ | | | | common causes | - Novobiocin | | | | (after E. coli) | resistant. | | +-----------------+-----------------+-----------------+-----------------+ | | | | | +-----------------+-----------------+-----------------+-----------------+ | **Streptococcus | \- Normally | \- Gram ⊕\ | \- No virulence | | Pneumoniae** | colonises | - | without | | | nasopharynx**[\ | Alpha-hemolytic | capsule. | | | Associations]{. | \ | | | | underline}**\ | **[Enzymes]{.un | | | | - Otitis media | derline}**\ | | | | (in children)\ | - Catalase ⊝\ | | | | - Meningitis\ | - Coagulase ⊝\ | | | | - Pneumonia\ | - Urease ⊝\ | | | | - Sinusitis\ | **[Shape]{.unde | | | | **[Presentation | rline}**\ | | | | ]** | - Lancet-shaped | | | | \ | diplococci A.\ | | | | - Pneumococcal | **[Virulence | | | | pneumonia is | Factors]{.under | | | | associated with | line}**\ | | | | "rusty" | - | | | | sputum.\ | Encapsulated.\ | | | | **[Vulnerable | - IgA protease\ | | | | Population]{.un | - Optochin | | | | derline}**\ | sensitive\ | | | | - Patients with | - Bile Soluble | | | | anatomic | | | | | hyposplenia\ | | | | | - Patients with | | | | | functional | | | | | hyposplenia\ | | | | | - Patients with | | | | | asplenia\ | | | | | **[Vaccines]{.u | | | | | nderline}**\ | | | | | - Pneumococcal | | | | | vaccines are | | | | | available in | | | | | both conjugate | | | | | (PCV13, PCV15, | | | | | PCV20) and | | | | | polysaccharide | | | | | (PPSV23) | | | | | formulations. | | | +-----------------+-----------------+-----------------+-----------------+ | **Streptococci | \- Normally | \- Gram ⊕\ | | | Viridans | colonises | - | | | group** | nasopharynx | Alpha-hemolytic | | | | [**\ | cocci.\ | | | | Streptococcus | **[Enzymes]{.un | | | | Mutans and | derline}**\ | | | | Streptococcus | - Catalase ⊝\ | | | | Mitis**]{.under | - Coagulase ⊝\ | | | | line}\ | - Urease ⊝\ | | | | - Dental | **[Virulence | | | | caries.\ | Factors]{.under | | | | **[Streptococcu | line}**\ | | | | s | - Optochin | | | | Sanguinis]{.und | resistant\ | | | | erline}**\ | - Bile | | | | - Makes | insoluble. | | | | dextrans that | | | | | bind to fibrin | | | | | platelet | | | | | aggregates on | | | | | damaged heart | | | | | valves\ | | | | | - Resulting in | | | | | infective | | | | | endocarditis. | | | +-----------------+-----------------+-----------------+-----------------+ | **Streptococcus | \- Normally | \- Gram ⊕\ | **[Key | | Pyogenes\ | colonises | - | virulence | | **(Group A | nasopharynx**[\ | Beta-hemolytic\ | factors]{.under | | streptococci) | Disease | **[Enzymes]{.un | line}**\ | | | Associations]{. | derline}**\ | - DNase\ | | | underline}**\ | - Catalase ⊝\ | - Erythrogenic | | | [1.Pyogenic]{.u | - Coagulase ⊝\ | exotoxin\ | | | nderline}\ | - Urease ⊝\ | - | | | - Pharyngitis\ | **[Shape]{.unde | Streptokinase\ | | | - Cellulitis\ | rline}**\ | - Streptolysin | | | - Impetigo | - Cocci in | O.\ | | | ("honey-crusted | chains\ | - ASO titer or | | | " | - Bacitracin | anti-DNase B | | | lesions)\ | sensitive,\ | antibodies | | | - Erysipelas\ | **[Virulence | indicate recent | | | [2.Toxigenic]{. | Factors]{.under | S pyogenes | | | underline}\ | line}**\ | infection.\ | | | - Scarlet | - Pyrrolidonyl | **[Scarlet | | | fever\ | Arylamidase | fever]{.underli | | | - Toxic | (PYR) | ne}**\ | | | shock--like | positive.\ | [Presentation]{ | | | syndrome\ | - Hyaluronic |.underline}\ | | | - Necrotizing | acid capsule | - Blanching\ | | | fasciitis\ | and\ | - Sandpaper | | | [3.Immunologic] | - M protein | like body rash\ | | | | inhibit | - Strawberry | | | | phagocytosis.\ | tongue\ | | | \- Rheumatic | - Antibodies to | - Circumoral | | | fever\ | M protein | pallor in the | | | - | enhance host | setting of | | | Glomerulonephri | defenses. | group A | | | tis\ | | streptococcal | | | **[Structure]{. | | pharyngitis | | | underline}**\ | | (erythrogenic | | | - Similar to | | toxin ⊕) | | | host proteins | | | | | (ie, myosin)\ | | | | | - Can lead to | | | | | autoimmunity | | | | | (ie, carditis | | | | | seen in acute | | | | | rheumatic | | | | | fever).\ | | | | | **[Diagnosis]{. | | | | | underline}**\ | | | | | - Diagnose | | | | | strep | | | | | pharyngitis via | | | | | throat swab, | | | | | which can be | | | | | tested with an | | | | | antigen | | | | | detection assay | | | | | (rapid, | | | | | in-office | | | | | results) or | | | | | cultured on | | | | | blood agar | | | | | (results in 48 | | | | | hours). | | | +-----------------+-----------------+-----------------+-----------------+ | | | | | +-----------------+-----------------+-----------------+-----------------+ | **Streptococcus | \- Normally | **[Polysacchari | \- Screen | | Agalactiae\ | colonizes | de | pregnant | | **(Group B | vagina\ | capsule.]{.unde | patients at | | streptococci) | **[CAMP | rline}**\ | 35--37 weeks of | | | Factor]{.underl | - Hippurate | gestation with | | | ine}**\ | test ⊕.\ | rectal and | | | - Produces CAMP | - Pyrrolidonyl | vaginal swabs.\ | | | factor, which | Arylamidase | **[Antibiotic | | | enlarges the | (PYR) positive. | Prophylaxis]{.u | | | area of | | nderline}**\ | | | hemolysis | | - Patients with | | | formed by S | | ⊕ culture | | | aureus.\ | | receive | | | - CAMP stands | | intrapartum | | | for the aut