Bacteria Comparison - MicrobeMaster Hub

Gram-Positive Cocci (GPC)

Category / Feature	Staphylococcus aureus	Streptococcus pyogenes (GAS)	Streptococcus pneumoniae
I. Introduction
Discovery/Naming	Discovered by A. Ogston (1880)Sir Alexander Ogston identified it in surgical abscesses. Rosenbach later named it aureus (1884) from Latin for 'golden', due to colony pigment. A major opportunistic pathogen.	Described by T. Billroth (1874)Theodor Billroth described cocci from erysipelas. Pasteur later named genus Streptococcus from Greek for 'twisted berry/chain'. Significant human pathogen.	Isolated by Pasteur/Sternberg (1881)Independently isolated from saliva by Louis Pasteur and George Sternberg. Initially called Diplococcus pneumoniae. Key cause of pneumonia.
Taxonomy Snippet	Genus Staphylococcus ("Bunch of Grapes")Greek staphyle (bunch of grapes) reflects cluster arrangement. Family Staphylococcaceae. Compare vs Coagulase-Negative Staphylococci like S. epidermidis.	Genus Streptococcus ("Twisted Chain")Greek streptos (twisted) reflects chain arrangement. Family Streptococcaceae. Compare vs S. agalactiae (Group B Strep), Viridans group streptococci.	Species pneumoniae ("Lung")Member of Streptococcus genus, within the Mitis group of Viridans streptococci. Distinguished by specific features.
Key ID Grouping	Coagulase Positive StaphylococcusPrimary clinical differentiator from other staphylococci (CoNS). Many strains also produce golden pigment (staphyloxanthin).	Lancefield Group A Streptococcus (GAS)Defined by the Group A carbohydrate antigen in its cell wall. Prototype β-hemolytic Streptococcus.	Alpha-Hemolytic Streptococcus (Pneumococcus)Typically lacks Lancefield group antigens. Key α-hemolytic species identified by optochin susceptibility and bile solubility.
Epidemiology Snippet	Common Hospital- & Community-Acquired InfectionsFrequent human colonizer (anterior nares, skin). Causes opportunistic infections globally. Methicillin-Resistant S. aureus (MRSA) is a major public health concern.	Human Reservoir; Causes Pharyngitis/Skin InfectionsSpread person-to-person via respiratory droplets or direct contact. Leading bacterial cause of pharyngitis ("strep throat") and common cause of skin infections (impetigo, erysipelas, cellulitis).	Nasopharyngeal Carriage Common; Endogenous SourceCarried in upper respiratory tract by many healthy individuals. Infection often follows aspiration into lungs or spread to adjacent sites (ears, sinuses), especially after viral illness or with host risk factors.
Primary Distinction Test	Catalase PositiveProduces catalase enzyme (bubbles with H₂O₂). Differentiates all Staphylococci from Streptococci and Enterococci.	Catalase Negative; β-HemolyticLacks catalase. Complete clearing (beta-hemolysis) on blood agar is characteristic.	Catalase Negative; α-HemolyticLacks catalase. Partial, greenish hemolysis (alpha-hemolysis) on blood agar is characteristic.
II. Morphology
Gram Stain & Shape	Gram(+) Cocci in ClustersSpherical cells dividing in multiple planes form grape-like clusters.	Gram(+) Cocci in ChainsSpherical/ovoid cells dividing in one plane form pairs and chains.	Gram(+) Lancet-shaped DiplococciOvoid cocci, often in pairs (diplococci) with slightly pointed adjacent ends ('lancet' shape). Can form short chains.
Motility/Spores	Non-Motile, Non-Spore-FormingLacks flagella, does not form endospores.	Non-Motile, Non-Spore-FormingLacks flagella, does not form endospores.	Non-Motile, Non-Spore-FormingLacks flagella, does not form endospores.
Capsule Presence	Microcapsule Present (Variable)Often a thin polysaccharide capsule (serotypes 5 and 8 most common). Contributes to virulence and biofilm formation.	Hyaluronic Acid Capsule (Mucoid Strains)Some strains have a capsule of hyaluronic acid, which is non-immunogenic (host mimicry) and anti-phagocytic. Gives mucoid appearance.	Polysaccharide Capsule Present (Key Virulence Factor!)Major virulence factor. Anti-phagocytic. Basis for >90 distinct serotypes, used in vaccine formulations.
III. Culture Characteristics
Atmosphere/Growth	Facultative Anaerobe; Grows EasilyGrows readily on basic laboratory media like Blood Agar and Nutrient Agar, with or without oxygen.	Facultative Anaerobe; Needs EnrichmentRequires enriched media (Blood Agar) for optimal growth. Growth often enhanced by CO₂ atmosphere.	Facultative Anaerobe; Needs CO₂ & EnrichmentConsidered capnophilic (requires 5-10% CO₂). Needs enriched media (Blood or Chocolate Agar).
Colony Appearance	Medium; Golden/White; Opaque; ButteryTypically 1-3 mm colonies. Staphyloxanthin pigment gives yellow color in many strains. Smooth, convex.	Small (Pinpoint); Gray-White; TranslucentOften less than 1 mm colonies. Typically associated with a relatively large zone of beta-hemolysis. Matte or glossy surface.	Small; Grayish; Umbilicated ('Draughtsman')Around 1 mm colonies, alpha-hemolytic. Older colonies often show central depression (autolysis). Mucoid if heavily encapsulated.
Hemolysis (Blood Agar)	Beta-Hemolysis (Complete Clearing)Typically complete lysis of red blood cells due to production of hemolysins (e.g., alpha-toxin).	Beta-Hemolysis (Strong, Wide Zone)Characteristically strong and wide zone of complete lysis due to Streptolysin S and O.	Alpha-Hemolysis (Partial, Greenish)Incomplete lysis with green zone due to H₂O₂ production converting hemoglobin to methemoglobin.
Selective Medium Reaction	Grows on Mannitol Salt Agar (+ Mannitol Fermentation)Salt tolerant (grows). Ferments mannitol, turning phenol red indicator yellow around colonies.	Inhibited by High Salt (No Growth on MSA)Does not tolerate high salt concentrations of Mannitol Salt Agar.	Inhibited by High Salt (No Growth on MSA)Does not tolerate high salt concentrations of Mannitol Salt Agar.
IV. Key Biochemical Identifiers
Catalase Test	Catalase [+]Bubbles form with H₂O₂. Key differentiator for Staphylococci.	Catalase [-]No bubbles with H₂O₂. Typical for Streptococci.	Catalase [-]No bubbles with H₂O₂.
Coagulase Test	Coagulase [+] (Key ID)Clots plasma. Defines S. aureus versus Coagulase-Negative Staphylococci.	Coagulase [-]Does not clot plasma.	Coagulase [-]Does not clot plasma.
PYR Hydrolysis	PYR [-]Does not hydrolyze L-pyrrolidonyl-β-naphthylamide.	PYR [+] (Key ID)Hydrolyzes substrate (red color). Key ID for GAS and Enterococcus.	PYR [-]Does not hydrolyze substrate.
Bacitracin Susceptibility ('A' Disk)	Resistant [R]Not inhibited by 0.04 U Bacitracin disk.	Susceptible [S]Inhibited (zone). Presumptive ID for Group A Streptococcus.	Resistant [R]Not inhibited by Bacitracin disk.
Optochin Susceptibility ('P' Disk)	Resistant [R]Not inhibited by Optochin disk.	Resistant [R]Not inhibited by Optochin disk.	Susceptible [S] (Key ID)Inhibited (zone ≥14mm). Key ID for S. pneumoniae.
Bile Solubility	Insoluble [-]Does not lyse in bile salts (remains turbid).	Insoluble [-]Does not lyse in bile salts.	Soluble [+] (Key ID)Lysed by bile salts (clearing). Key ID for S. pneumoniae.
V. Key Virulence Factors
Adherence/Colonization	MSCRAMMs (e.g., FnBPs), Protein ASurface proteins bind host matrix molecules. Protein A binds antibodies. Biofilm formation aids colonization.	M Protein, Lipoteichoic Acid (LTA), Protein FMediate adherence to epithelial cells, fibrinogen binding (M Protein).	Adhesins (PsaA, PspC/CbpA...), PiliBind to host cell receptors (e.g., pIgR), mucus. Choline Binding Proteins anchor adhesins.
Immune Evasion	Protein A (Binds IgG Fc), CapsuleProtein A prevents opsonization. Capsule inhibits phagocytosis. Coagulase may form protective clot.	M Protein (Anti-phagocytic!), HA Capsule, C5a PeptidaseM protein inhibits complement/phagocytosis. Hyaluronic acid capsule camouflages. C5a peptidase dampens neutrophil recruitment.	Polysaccharide Capsule!, PspA, IgA ProteaseCapsule is primary anti-phagocytic factor. PspA inhibits complement. IgA protease cleaves IgA on mucosa.
Cytotoxins	Alpha, Beta, Delta, Gamma Toxins; PVLDamage host cell membranes. Alpha toxin key pore-former. Panton-Valentine Leukocidin linked to severe infections.	Streptolysin O (SLO) & Streptolysin S (SLS)Pore-forming toxins lyse RBCs, WBCs. SLO antigenic (ASO test). SLS oxygen-stable hemolysin.	Pneumolysin (PLY) (Major Toxin!)Major cytotoxin released on lysis. Cholesterol-dependent pore-former, damages respiratory cells, triggers inflammation.
Superantigens	TSST-1, Staphylococcal Enterotoxins (SEs)Cause non-specific T-cell activation, massive cytokine release (Toxic Shock Syndrome, Food Poisoning effects).	Strep Pyrogenic Exotoxins (SpeA, C, F...)Cause rash of Scarlet Fever, contribute to Strep Toxic Shock Syndrome (STSS).	Not ApplicableS. pneumoniae does not produce recognized superantigens.
Other Key Toxins/Enzymes	Exfoliative Toxins (ETA/B); Spreading FactorsETA/B cause Scalded Skin Syndrome. Hyaluronidase, Kinase, Lipase, DNase aid spread/damage.	SpeB (Cysteine Protease); Spreading FactorsSpeB crucial for tissue destruction (Necrotizing Fasciitis). Streptokinase, Hyaluronidase, DNases aid spread.	Autolysin (LytA); NeuraminidaseLytA releases Pneumolysin. Neuraminidase aids spread/adherence. Hyaluronidase present.
VI. Pathogenesis & Disease
Hallmark Lesion	Abscess (Localized Pus Collection)Coagulase aids localization. Necrosis surrounded by inflammation.	Spreading Inflammation (Cellulitis/Erysipelas)Rapid spread through tissues aided by enzymes. Less localized than Staph abscess.	Lobar Consolidation (Pneumonia)Alveoli fill with edema fluid, RBCs, PMNs due to inflammation/bacterial products.
Key Local Diseases	Skin/Soft Tissue Infections (Boils, Impetigo!)Most common cause of folliculitis, furuncles, carbuncles, wound infections.	Pharyngitis ("Strep Throat")!, Impetigo, CellulitisLeading bacterial cause of pharyngitis. Also erysipelas.	Otitis Media!, Sinusitis, ConjunctivitisLeading bacterial cause of middle ear and sinus infections.
Key Invasive Diseases	Bacteremia/Sepsis, Endocarditis, Pneumonia, OsteomyelitisSerious bloodstream infections and seeding of distant sites.	Necrotizing Fasciitis!, Bacteremia/Sepsis, PneumoniaLife-threatening deep tissue infection. Can cause severe sepsis.	Pneumonia!, Meningitis!, Bacteremia/SepsisMost common bacterial Community-Acquired Pneumonia cause. Leading cause of bacterial meningitis (post-Hib vaccine).
Key Toxin-Mediated Syndromes	Toxic Shock Syndrome!, Scalded Skin!, Food PoisoningSystemic effects caused by TSST-1, Exfoliatins, or Enterotoxins respectively.	Scarlet Fever!, Strep Toxic Shock Syndrome!Rash related to Spe production. Severe systemic illness with invasive disease.	Not ApplicablePneumococcal disease primarily driven by inflammation and direct cytotoxicity of Pneumolysin.
Immunologic Sequelae	Not CharacteristicPost-infectious immune syndromes are not typically associated with S. aureus.	Acute Rheumatic Fever! Glomerulonephritis! (Critical!)ARF follows pharyngitis; PSGN follows pharyngitis or skin infection. Caused by immune response (cross-reaction / immune complexes).	Not CharacteristicPost-infectious immune syndromes are not associated with S. pneumoniae.
VII. Laboratory Diagnosis
Microscopy Finding	Gram(+) Cocci in Clusters (clinical site)Direct Gram stain highly suggestive if seen with PMNs in pus.	Gram(+) Cocci in Chains (often unreliable)May be seen in clinical samples, but less reliable/sensitive than culture.	Gram(+) Lancet Diplococci (CSF, Sputum)Highly suggestive, especially in CSF Gram stain for meningitis.
Culture & Identification Keys	Catalase(+), Coagulase(+), MSA(+) YellowStandard identification pathway for S. aureus.	β-hemolysis, Catalase(-), Bacitracin(S), PYR(+)Typical findings for Group A Streptococcus confirmation.	α-hemolysis, Catalase(-), Optochin(S), Bile Soluble(+)Required tests to differentiate S. pneumoniae from Viridans streptococci.
Rapid Diagnostic Tests	Rapid Coagulase/Latex; PCR (MRSA detection)Tests for specific surface components or mecA gene. MALDI-TOF rapid ID from culture.	Rapid Antigen Detection Test (RADT) (Throat Swab)Detects Group A antigen directly from swab; useful for rapid diagnosis of pharyngitis.	Urine Antigen Test; CSF Antigen/PCRUrine antigen useful for adult pneumonia. CSF tests aid meningitis diagnosis.
VIII. Treatment
Drug of Choice (Susceptible)	Anti-Staph Penicillin (e.g., Nafcillin) / CephalosporinFor Methicillin-Susceptible S. aureus (MSSA).	Penicillin or Amoxicillin (Still!)Still uniformly susceptible; preferred narrow-spectrum agents.	Penicillin or Amoxicillin (IF susceptible)Use depends on susceptibility results; resistance common.
Treatment for Resistant Strains	MRSA: Vancomycin (Severe); Oral (Clinda, TMP-SMX, Doxy)Vancomycin standard for invasive MRSA. Community SSTI options vary. Linezolid, Daptomycin alternatives.	Macrolide (e.g., Azithromycin) or Clindamycin (Pen Allergy)Check susceptibility as resistance exists. Cephalosporins possible for non-anaphylactic allergy.	Ceftriaxone, Resp. Fluoroquinolone, VancoChoice depends on MIC/resistance & site (esp. meningitis). Combo may be needed.
Important Adjunctive Therapy	Incision & Drainage of Abscesses!Crucial for localized collections of pus.	Surgical Debridement for Necrotizing Fasciitis!Urgent removal of dead tissue is life-saving.	Supportive Care; Dexamethasone (Meningitis)Maintain oxygenation. Steroids reduce inflammation/sequelae in meningitis.
IX. Prophylaxis
Vaccine Availability	None Currently EffectiveNo licensed vaccine provides broad protection despite efforts.	None AvailableNo vaccine currently available (M protein diversity a challenge).	Yes! Pneumococcal Vaccines (Conjugate & Polysaccharide)PCV (infants/adults) and PPSV23 (adults/risk groups) target capsular polysaccharides. Highly effective.
Chemoprophylaxis Uses	MRSA Decolonization (Situational)Nasal Mupirocin +/- CHG washes in specific high-risk scenarios (e.g., pre-surgery).	Penicillin for Rheumatic Fever Recurrence PreventionLong-term prophylaxis needed after episode of Acute Rheumatic Fever.	Penicillin for Asplenia/Splenic DysfunctionTo prevent overwhelming post-splenectomy infection (OPSI).

Gram-Negative Cocci (GNC)

Category / Feature	Neisseria gonorrhoeae	Neisseria meningitidis
I. Introduction & Morphology
Gram Stain & Shape	Gram [-] Kidney-bean DiplococciPairs of cocci with adjacent sides flattened. Often found intracellularly within neutrophils in urethral exudate.	Gram [-] Kidney-bean DiplococciSimilar morphology to gonococcus. Often found intracellularly and extracellularly in cerebrospinal fluid during meningitis.
Oxidase / Catalase	Oxidase [+], Catalase [+]Key reactions for Neisseria species identification.	Oxidase [+], Catalase [+]Similar reactivity to gonococcus.
Capsule	No Polysaccharide CapsuleVirulence relies more on pili and outer membrane proteins.	Yes, Polysaccharide Capsule! (Vaccine Target!)Major virulence factor, anti-phagocytic. Basis for serogrouping (A,B,C,Y,W-135) and conjugate vaccines.
II. Culture & Biochemistry
Culture Media/Atmosphere	Chocolate Agar; Needs Selective Media (e.g., Thayer-Martin); Needs CO₂Fastidious growth requires enriched media and incubation in increased CO₂ (capnophilic). Selective media necessary to inhibit normal flora from GU tract sites.	Chocolate or Blood Agar; Needs CO₂Also capnophilic. Grows on standard enriched media as typically isolated from sterile sites (blood, CSF).
Sugar Fermentation (Oxidation)	Glucose ONLY UtilizedKey biochemical differentiator. Oxidizes glucose, but not maltose or sucrose.	Glucose AND Maltose Utilized!Key biochemical differentiator from N. gonorrhoeae. Oxidizes both glucose and maltose.
III. Virulence & Disease
Key Virulence Factors	Pili (variation!), Opa proteins, IgA Protease, LOSPili allow attachment and undergo high frequency antigenic variation aiding immune evasion. Opa proteins involved in adherence/invasion. LOS (Lipooligosaccharide) is endotoxic.	CAPSULE!, Pili, Opa proteins, IgA Protease, LOSThe polysaccharide capsule is paramount for invasive disease, preventing phagocytosis. Pili, Opa, IgA Protease similar. LOS release is major driver of sepsis/shock.
Common Diseases	Gonorrhea (Urethritis, Cervicitis etc.), PID, DGI, Ophthalmia NeonatorumCauses range of GU tract infections, can disseminate (DGI), cause Pelvic Inflammatory Disease, or neonatal conjunctivitis.	Meningitis!, Meningococcemia! (Sepsis)Causes potentially fatal bacterial meningitis and/or overwhelming sepsis, often associated with a petechial/purpuric rash due to LOS-induced vascular damage.
Transmission	Sexual ContactSpread via vaginal, anal, or oral sexual contact.	Respiratory DropletsSpread through close contact via respiratory/throat secretions from carriers or cases.
IV. Laboratory Diagnosis
Primary Diagnostic Approach	NAAT (Nucleic Acid Amplification Test)!Preferred method (urine, swabs) due to high sensitivity. Gram stain useful in symptomatic males. Culture needed for susceptibility testing.	CSF/Blood Culture & Gram Stain!Isolation from normally sterile sites is gold standard. Gram stain of CSF is critical for rapid presumptive ID. PCR/Antigen tests on CSF supportive.
V. Treatment
Treatment	Ceftriaxone (High Dose); Resistance Rising!Due to widespread resistance, high-dose IM Ceftriaxone currently recommended, often with co-treatment for Chlamydia. Susceptibility testing crucial.	Ceftriaxone (IV) or Penicillin G (if susceptible)Third-gen cephalosporins used empirically. Penicillin can be used if proven susceptible. Supportive care essential.
VI. Prophylaxis
Vaccine Availability	NoneVaccine development challenging due to antigenic variation.	Yes! (Conjugate ACWY & Protein MenB)Effective vaccines targeting major capsular serogroups available and recommended.
Chemoprophylaxis	No Routine (Partner Tx is Key)Treatment of sexual partners is the strategy.	Yes! For Close ContactsAntibiotics (Rifampin, Cipro, Ceftriaxone) given to close contacts to eradicate carriage and prevent disease.

Gram-Positive Rods (GPR)

Category / Feature	Corynebacterium diphtheriae	Clostridium tetani	Clostridium botulinum	Clostridium perfringens	Clostridioides difficile
I. Introduction & Morphology
Gram Stain & Shape	G[+] Pleomorphic Rod (Club, Palisades)Variable staining. Irregular 'Chinese letter' or parallel (palisade) arrangements common. May see metachromatic granules.	G[+] Slender Rod w/ Terminal SporeGram stain may be variable. Spore gives characteristic 'drumstick' appearance. Flagellated.	G[+] Rod w/ Subterminal SporeOval, subterminal spores often visible. Flagellated.	G[+] Large "Boxcar" RodRelatively large, rectangular-appearing rods. Spores rarely seen in clinical samples/routine culture. Non-motile. Often encapsulated in vivo.	G[+] Rod w/ Subterminal SporeSpores readily formed, allows persistence/transmission. Flagellated. Gram stain can be variable.
Oxygen Requirement	Aerobe / Facultative AnaerobeGrows well in presence of oxygen.	Obligate (Strict) AnaerobeRequires complete absence of oxygen for growth. Oxygen is toxic.	Obligate (Strict) AnaerobeRequires strict anaerobic conditions.	Aerotolerant AnaerobePrefers anaerobic but can survive brief oxygen exposure. Grows extremely rapidly anaerobically.	Obligate (Strict) AnaerobeRequires strict anaerobic conditions.
II. Culture & Key Identification
Culture Notes	Grows on BA; Selective: Tellurite Agar (Black colonies)Loeffler's medium enhances granule formation. Cystine-Tellurite Blood Agar (CTBA) is selective.	Difficult/Slow; Anaerobic BA; RCM BrothSwarming on agar may occur. Hemolysis common. Hard to isolate.	Difficult/Slow; Anaerobic Media (Egg Yolk Agar - Lipase)Requires specialized anaerobic techniques. Lipase activity (+) on egg yolk agar helpful for Group I strains.	RAPID Growth!; Anaerobic BA; Double Zone Hemolysis!Very fast doubling time. Characteristic target-like dual zone of hemolysis (inner beta, outer alpha) highly suggestive. Stormy fermentation in milk.	Difficult; Selective CCFA Agar (Yellow, "Horse Manure" Smell)Requires anaerobic conditions. Cycloserine-Cefoxitin-Fructose Agar (CCFA) inhibits fecal flora. Produces characteristic odor.
Key Biochemicals	Catalase[+], Nitrate Reduct[+], Urease[-]Ferments glucose/maltose. Essential test: Elek test or PCR for toxin production.	Catalase[-], Indole[-]Relatively inert biochemically. Proteolytic. Diagnosis rarely relies on biochemistry.	Catalase[-], Variable ferm/proteolysisDiverse groups (I-IV). Lipase useful. Primary ID often involves toxin detection.	Catalase[-], Lecithinase(+) (Nagler test), Ferments Sugars (Gas!)Strong fermentation. Gelatinase(+). Nagler test confirms alpha-toxin lecithinase activity.	Catalase[-], Indole[-]Identified by toxin assays/NAAT, or specific culture characteristics.
III. Key Toxins & Disease
Primary Toxin(s)	Diphtheria Toxin (DT)A-B toxin; inhibits protein synthesis (ADP-ribosylates EF-2). Phage-encoded. Causes local tissue necrosis & systemic effects.	Tetanospasmin (TeNT)A-B neurotoxin; blocks inhibitory neurotransmitter release (glycine/GABA) in CNS -> spastic paralysis. Plasmid-encoded.	Botulinum Neurotoxin (BoNT)Potent A-B neurotoxin (multiple types A-G); blocks Acetylcholine release at neuromuscular junction -> flaccid paralysis.	Alpha Toxin (CPA); Enterotoxin (CPE); OthersCPA=Phospholipase C/Lecithinase, key for myonecrosis. CPE causes food poisoning diarrhea. Beta, Epsilon, Iota toxins important in some settings.	Toxin A (TcdA Enterotoxin) & Toxin B (TcdB Cytotoxin)Large glucosylating toxins disrupting cytoskeleton, tight junctions causing enterocyte death/inflammation/fluid secretion. Binary toxin (CDT) in some strains.
Primary Disease(s)	Diphtheria (Respiratory or Cutaneous)Pseudomembrane in pharynx (potential airway obstruction), systemic cardiac/neurologic toxicity.	Tetanus (Spastic Paralysis)"Lockjaw", opisthotonos, muscle rigidity/spasms, autonomic dysfunction.	Botulism (Flaccid Paralysis)Descending paralysis (Foodborne, Infant, Wound forms). Respiratory failure is major risk.	Gas Gangrene (Myonecrosis); Food PoisoningRapidly progressive muscle necrosis with crepitus (gas). Self-limited watery diarrhea (Type A food poisoning). Type C causes necrotizing enteritis ('pigbel').	Antibiotic-Associated Diarrhea (AAD); Pseudomembranous Colitis (CDI)Spectrum from mild diarrhea to severe, potentially fatal colitis (PMC) following disruption of gut flora by antibiotics.
IV. Laboratory Diagnosis
Diagnostic Approach	Culture (Tellurite) + TOXIN Detection (Elek/PCR)!Clinical suspicion important. Must isolate organism AND prove it produces toxin.	Clinical Diagnosis Primary!; Culture Difficult/Rarely DoneBased on history and symptoms. Lab confirmation usually not feasible/necessary for treatment decisions.	Clinical Dx; Toxin Detection in Serum/Stool/Food!Mouse bioassay historically used. Immunoassays/PCR for toxin types becoming more common. Culture supports diagnosis.	Clinical Picture (Gas Gangrene); Anaerobic Culture (Blood Agar); Toxin Assay (Stool/Food)Gas gangrene often diagnosed clinically +/- imaging. Gram stain of tissue revealing large GPRs supportive. Nagler useful. CPE toxin assay for food poisoning confirmation.	Toxin Detection or Toxigenic Culture/NAAT in Stool!Modern approach involves multi-step algorithm: often start with sensitive GDH antigen test +/- Toxin EIA. NAAT (PCR) for toxin genes (tcdA/tcdB) is highly sensitive/specific. Culture possible but less routine.
V. Treatment
Key Treatment Modality	Antitoxin (DAT)! + Antibiotics (Erythromycin/Penicillin)Neutralizing antitoxin is crucial. Antibiotics eradicate bacteria. Airway management vital if needed.	Antitoxin (TIG)! + Antibiotics (Metronidazole/Penicillin) + Spasm ControlHuman Tetanus Immune Globulin. Wound debridement. Benzodiazepines/muscle relaxants. Supportive care.	Antitoxin! + Respiratory Support!Equine antitoxin (or BabyBIG). Mechanical ventilation often required. Antibiotics only for wound botulism to clear organism.	SURGICAL Debridement! (Gas Gangrene) + Antibiotics (Penicillin + Clindamycin)Urgent surgery essential. Hyperbaric O₂ controversial adjunct. Food poisoning supportive care only.	Oral Vancomycin or FidaxomicinStop inciting antibiotic if possible. Metronidazole less preferred now. Fecal Microbiota Transplant (FMT) highly effective for recurrent CDI. Bezlotoxumab (anti-TcdB MAb) reduces recurrence.
VI. Prophylaxis & Prevention
Vaccine	Yes! (Diphtheria Toxoid - DTaP/Tdap/Td)Highly effective component of routine immunizations.	Yes! (Tetanus Toxoid - DTaP/Tdap/Td)Highly effective. Requires periodic boosters (Tdap/Td) throughout life.	No (Routine Human Vaccine)Toxoid exists but not routinely used.	No (Human Vaccine)Veterinary vaccines exist for animals.	NoVaccines under development but none licensed.
Other Prevention	Vaccination; Respiratory IsolationMaintain high vaccination rates. Isolate active cases.	Vaccination; Proper Wound Care; TIG/Boosters Post-ExposureEnsure tetanus immunization up-to-date. Clean wounds. Assess need for TIG +/- booster after injury.	Proper Food Canning/Heating; Avoid Honey (<1yr)Heating food adequately destroys toxin. Avoid potentially contaminated honey for infants.	Proper Wound Care; Safe Food Temps (Reheating/Holding)Prevent wound contamination. Proper food handling to prevent spore germination/toxin production for food poisoning.	ANTIBIOTIC STEWARDSHIP!; Infection Control (Contact Precautions, HANDWASHING-Soap/Water!, Bleach Cleaning)Using antibiotics judiciously is key primary prevention. Spores resist alcohol; physical washing + bleach disinfection needed.

Enterobacteriaceae (Enteric Gram-Negative Rods)

Category / Feature	Escherichia coli	Klebsiella pneumoniae	Proteus mirabilis	Salmonella enterica	Shigella spp.
I. Key Biochemical Identifiers
Lactose Ferm (MacConkey)	LF [+] (Pink/Red)Rapid fermentation -> pink colonies.	LF [+] (MUCOID Pink)Lactose fermenter, often highly mucoid colonies due to capsule.	Non-LF [-] (Pale)Pale colonies, may exhibit swarming motility.	Non-LF [-] (Pale)Pale colonies.	Non-LF [-] (Pale)Pale colonies. S. sonnei is late LF (+).
Indole (IMViC 'I')	Indole [+] (Key ID)Tryptophanase positive (red ring w/ Kovac's).	Indole [-]Tryptophanase negative.	Indole [-] (P. mirabilis)P. vulgaris is positive.	Indole [-]Tryptophanase negative.	Indole [-] (Most)S. sonnei can be variable/positive.
Citrate Use (IMViC 'C')	Citrate [-]Cannot use citrate as sole carbon source (green on Simmons).	Citrate [+]Can utilize citrate (blue on Simmons).	Citrate [+]Usually utilizes citrate.	Citrate [+]Usually utilizes citrate.	Citrate [-]Cannot utilize citrate.
Urease	Urease [-]No urease production.	Urease [+] (Variable Speed)Produces urease, but often slower than Proteus.	Urease RAPID [+]!Characteristic strong, rapid urease activity (bright pink).	Urease [-]No urease production.	Urease [-]No urease production.
H₂S Production (TSI Agar)	H₂S [-]No black precipitate in TSI butt.	H₂S [-]No H₂S production.	H₂S [+]Produces H₂S (blackening of TSI butt).	H₂S [+]! (Key ID vs Shigella)Characteristic H₂S production (black butt). S. Typhi variable/weak.	H₂S [-]! (Key ID vs Salmonella)Does not produce H₂S.
Motility	Motile [+] (Most)Typical peritrichous flagella.	NON-MOTILE [-]!Key differentiating feature.	HIGHLY Motile [++] (SWARMING!)Characteristic swarming growth on agar plates.	Motile [+] (Most)Typical peritrichous flagella.	NON-MOTILE [-]!Key differentiating feature.
II. Key Virulence & Disease Association
Virulence Mechanisms	Adhesins (Pili!), LPS, Toxins (Variable!), Capsule (K1)Diverse mechanisms depending on pathotype (e.g., LT/ST, Shiga Toxin, Hemolysin). Adherence critical for UTI.	CAPSULE! (Major VF), Adhesins, LPS, SiderophoresThick capsule protects from phagocytosis/complement. Adherence factors important. Iron acquisition systems.	Urease! (-> Stones!), Motility!, Adhesins, LPS, IgA ProteaseUrease causes alkalinization, promotes struvite stone formation. Swarming motility aids ascent. Biofilm.	Invasion! (T3SS-1), Intracellular Survival (T3SS-2, Typhi), LPS, Flagella, Vi Capsule (Typhi)Ability to invade gut cells and survive in macrophages is central to pathogenesis.	Invasion! (T3SS injecting Ipa proteins), Intracellular Spread! (Actin), Shiga Toxin (some)Highly adapted for epithelial cell invasion and cell-to-cell spread causing mucosal destruction. Low infectious dose.
Common Clinical Settings	UTI!, Diarrhea (Traveler's, Foodborne), Neonatal Sepsis/MeningitisMost common cause of uncomplicated UTIs. Major cause of various diarrheal syndromes worldwide. K1 strains cause severe neonatal infections.	Pneumonia (HAP/VAP/Alcoholic), UTI (Catheter), Sepsis, Liver AbscessOften associated with healthcare settings, compromised hosts. Classic cause of lobar pneumonia with "currant jelly" sputum.	UTI! (Complicated/Catheter-Associated), Kidney StonesSignificant cause of UTIs, especially when structural abnormalities or devices are present. Strong association with stone formation.	Gastroenteritis (Poultry/Eggs); Enteric Fever (Typhoid)Common foodborne diarrheal illness (non-typhoidal). Systemic illness caused by specific serovars (typhoidal).	Dysentery (Bacillary)!; Daycare OutbreaksClassic inflammatory colitis with fever, cramps, bloody/mucoid stool. Highly contagious, outbreaks common where hygiene is poor.
III. Resistance & Prevention Notes
Antibiotic Resistance Profile	HIGH Resistance! (β-lactamases incl ESBL, FQ-R)Significant resistance burden worldwide. Susceptibility testing crucial. Carbapenem resistance emerging.	VERY HIGH Resistance! (ESBLs, KPC/NDM Carbapenemases -> CRE!!)A major reservoir of multi-drug resistance, especially Carbapenem-Resistant Enterobacteriaceae (CRE). Often limited therapeutic options.	Increasing Resistance (FQ, TMP-SMX); ESBLs presentSusceptibility testing important, especially for complicated infections.	Rising Fluoroquinolone Resistance! (Especially Typhoid)Resistance complicates treatment of enteric fever significantly. Resistance also common to older drugs.	Rising Fluoroquinolone & Azithromycin Resistance!Reduces treatment options, especially for travel-associated infections. Check local patterns/susceptibility if treating.
Prevention Highlights	Hygiene, Safe Food/Water, UTI Prevention StrategiesCook food properly, avoid contaminated water. For UTIs: hydration, proper hygiene.	INFECTION CONTROL! (Healthcare); Hand HygieneStrict contact precautions, environmental cleaning vital for preventing CRE spread. Antibiotic stewardship.	Catheter Care, Prompt Stone TreatmentMinimize catheter use, maintain closed drainage. Address underlying conditions causing stones.	Safe Food Handling!; Typhoid Vaccination! (Travelers/Endemic)Cook poultry/eggs well. Hygiene. Typhoid vaccines (injectable Vi polysaccharide or oral live attenuated) available.	HANDWASHING! SanitationStrict personal hygiene critical due to very low infectious dose required. Safe water/food important in endemic areas.

Other Clinically Significant Gram-Negative Rods

Category / Feature	Vibrio cholerae	Haemophilus influenzae	Bordetella pertussis	Brucella spp.
I. Morphology & Key ID
Gram Stain & Shape	G[-] Curved Rod (Comma)Characteristic shape, usually seen clearly.	G[-] Coccobacillus / Pleomorphic RodSmall, variable shape; can appear almost coccal or filamentous.	G[-] Tiny CoccobacillusVery small and stains faintly. May be missed on Gram stain.	G[-] Tiny CoccobacillusAlso very small and stains poorly with standard Gram stain.
Oxygen Requirement	Facultative AnaerobeCan grow with or without oxygen.	Facultative Anaerobe; CapnophilicPrefers increased CO₂.	Strict Aerobe!Requires oxygen for growth.	Strict Aerobe!Requires oxygen; some species (abortus) prefer CO₂ initially.
Oxidase Test	Oxidase [+]Key differentiator from Enterobacteriaceae.	Oxidase [Variable]Often positive, but can vary.	Oxidase [+]Positive result.	Oxidase [+]Positive result.
Special Growth Factors	No Special FactorsGrows readily on simple media, although selective media helps isolation.	Needs X Factor (Hemin) AND V Factor (NAD)!Will not grow on standard blood agar unless V factor supplied (e.g., by Staph satellitism). Grows on Chocolate Agar.	Needs Specialized Media! (e.g., Regan-Lowe, Bordet-Gengou)Highly fastidious; standard media are inhibitory. Charcoal or other substances needed.	Needs Enriched Media; Slow Growth! BSL-3!Requires Brucella agar or enriched blood agar. Takes days to weeks. Significant lab hazard.
II. Key Culture Characteristics
Appearance on Key Media	TCBS Agar -> Yellow ColoniesFerments sucrose on selective Thiosulfate Citrate Bile Sucrose agar. Grows well in alkaline conditions (APW broth enrichment).	Chocolate Agar -> Growth; Blood Agar -> No Growth (or Satellitism)Transparent, dewdrop-like colonies on Chocolate. Satellitism shows growth only near V-factor producing bacteria on BA.	Regan-Lowe -> Small "Mercury Drop" Colonies; Slow GrowthTiny, glistening, pearl-like colonies after 3-7+ days incubation.	Enriched Blood Agar -> Small, Non-hemolytic Colonies; Very SlowMay take several weeks to appear. Need to hold cultures long-term.
III. Key Virulence Factors
Primary Toxin(s) / VF	Cholera Toxin (CTX)!; Toxin Co-regulated Pili (TCP)CTX ADP-ribosylates Gs -> high cAMP -> massive Cl⁻/water secretion. TCP needed for colonization. Motility via flagellum also important.	Capsule (Type b = PRP)!; Pili; Adhesins (HMW); IgA Protease; LOSPRP capsule critical for invasive Hib disease. Pili/adhesins for respiratory tract attachment. LOS endotoxic. IgA protease helps mucosal survival.	Adhesins (FHA, PRN)!; Pertussis Toxin (PTx)!; Adenylate Cyclase Toxin (ACT); Tracheal Cytotoxin (TCT)Multiple factors damage respiratory epithelium (TCT), disrupt signaling (PTx, ACT -> ↑cAMP), and facilitate attachment (FHA, Pertactin).	Intracellular Survival (Macrophages)!; LPS (Smooth); Type IV Secretion System?Key is ability to survive/replicate within phagocytes by inhibiting phagolysosome fusion. Smooth LPS associated with virulence. T4SS may contribute. No major exotoxins.
IV. Disease & Diagnosis
Disease Caused	CholeraProfuse, dehydrating watery diarrhea ("rice water stool").	Meningitis/Epiglottitis (Hib, pre-vaccine); Otitis Media, Sinusitis, Pneumonia (NTHi)Disease pattern shifted significantly after widespread Hib vaccination. NTHi is common respiratory pathogen.	Pertussis (Whooping Cough)Characteristic paroxysmal cough with inspiratory 'whoop', vomiting. Can be severe/fatal in infants.	Brucellosis (Undulant Fever)Systemic febrile illness with sweats, malaise, often waxing/waning fever. Potential focal complications (bone/joint, endocarditis). Granuloma formation.
Primary Diagnostic Method	Stool Culture (TCBS); Rapid Ag TestsIsolation on selective media. Rapid tests available.	Culture (Chocolate Agar) + X/V Factors Test; PCRFrom relevant site (sputum, ear fluid, CSF). PCR useful.	PCR! (NP Swab/Aspirate); Culture less sensitive/slowNAAT is diagnostic standard now. Serology useful retrospectively/epidemiologically.	Blood Culture! (Prolonged); Serology! (MAT, ELISA)Requires holding blood cultures for weeks, BSL-3 handling. Serology essential. PCR available.
V. Treatment & Prevention
Treatment	REHYDRATION!; Doxycycline/Azithro/CiproFluid replacement is primary. Antibiotics reduce duration/volume of diarrhea.	Amoxicillin-Clavulanate / Cephalosporins (e.g., Cefixime/Ceftriaxone)Many strains produce β-lactamase, requiring alternatives to amoxicillin alone.	Macrolides (Azithromycin, Erythromycin)!; TMP-SMX altEarly treatment may shorten duration/reduce transmission. Treat close contacts prophylactically.	Doxycycline + (Rifampin or Aminoglycoside)! Long Duration!Combination therapy for 6+ weeks is essential to prevent relapse.
Prevention / Vaccine	Safe Water/Sanitation; Oral Cholera Vaccines (Targeted Use)OCVs useful in endemic areas/outbreaks.	Hib Conjugate Vaccine! (HIGHLY Effective vs Type b)Part of routine infant immunizations. No vaccine against NTHi.	Acellular Pertussis Vaccine! (DTaP/Tdap Boosters!)Routine immunization critical. Boosters needed due to waning immunity.	Animal Control!; Pasteurization!; Lab Safety! (No Human Vaccine)Prevent via pasteurizing dairy, occupational safety, controlling disease in animals.

Mycobacteria

Category / Feature	Mycobacterium tuberculosis complex	Mycobacterium leprae	Atypical Mycobacteria (NTM) Overview
I. Introduction & Morphology
Defining Feature	ACID-FAST Bacilli!; Causes Tuberculosis (TB)Waxy cell wall rich in mycolic acids resists Gram stain but retains carbolfuchsin after acid-alcohol wash (Ziehl-Neelsen/Kinyoun). Major global health problem.	ACID-FAST Bacilli!; Causes Leprosy; UnculturableAcid-fast but often stains weaker than MTB. Unique tropism for skin macrophages & peripheral nerve Schwann cells. Cannot be grown on artificial media.	ACID-FAST Bacilli!; Environmental; OpportunisticLarge group of environmental mycobacteria, classified by growth rate/pigment (Runyon). Cause disease mainly in susceptible hosts.
Morphology Notes	Slender Rods; May appear 'beaded'; Forms "Cords" in vitroCord factor (trehalose dimycolate) contributes to clumping/virulence.	Slender Rods; Often found in clumps ("Globi") within cellsCharacteristic large aggregates seen within macrophages, especially in lepromatous leprosy.	Morphology similar to MTB, variable lengthSpecific shapes not generally diagnostic for species ID within NTM.
II. Culture & Identification
Oxygen / Growth Rate	Obligate Aerobe; VERY Slow Grower! (Weeks)Needs oxygen. Generation time ~18-24 hours.	Obligate Intracellular; CANNOT Be Cultured In Vitro!Lacks genes for independent life. Grown in mouse footpad or armadillo model for research.	Aerobic; Variable Growth Rate! (Slow or Rapid)Major grouping: Slow Growers (>7 days for colonies) vs Rapid Growers (<7 days). Key for initial classification.
Media / ID Methods	Special Media (LJ, Middlebrook); NAAT from sample/culture!Complex egg (LJ) or agar (Middlebrook) based media. Automated liquid culture (MGIT) faster. NAAT (e.g., GeneXpert) is standard for rapid detection/RIF resistance. Traditional biochem (Niacin+) less used.	Diagnosis: Clinical + Skin Biopsy (AFB/Histology)!Relies on recognizing characteristic skin/nerve lesions plus visualizing AFB in slit skin smears or skin biopsy specimens. PCR possible but not standard.	Culture! + Molecular ID (Sequencing)!; Growth/Pigment helpsCulture essential. Runyon grouping (photo/scoto/non-chromogen, rapid/slow) useful start. Precise species ID by molecular methods (e.g., hsp65, rpoB, 16S sequencing, MALDI-TOF) needed for treatment.
III. Pathogenesis & Disease
Key Pathogenesis Feature	Intracellular Survival (Macrophages)!; Granuloma FormationResists killing within alveolar macrophages, inhibits phagolysosome fusion. Host CMI response forms granulomas to contain infection -> latent TB. Disease = breakdown of containment or primary progression.	Intracellular Survival (Macrophages & Schwann Cells!)!; Nerve DamageUnique ability to infect nerve cells directly leads to peripheral neuropathy. Cell wall lipids (PGL-1) interact with host cells. Host immune response determines clinical spectrum (Tuberculoid vs Lepromatous).	Variable: Intracellular Survival, Biofilm, ColonizationMechanisms differ. Many can survive in macrophages. Biofilm formation aids persistence (e.g., water pipes). Colonization may precede infection in susceptible hosts. Direct tissue damage can occur.
Disease Spectrum	Pulmonary Tuberculosis (Primary, Reactivation, Miliary); Extrapulmonary TB (Lymph, Bone, Meninges etc)Lungs most common site. Can spread hematogenously anywhere. Latent TB Infection (LTBI) = asymptomatic containment.	Leprosy (Hansen's Disease): Tuberculoid (Paucibacillary) <-> Lepromatous (Multibacillary) SpectrumDetermined by host cell-mediated immunity (Strong CMI=Tuberculoid, few lesions/bacilli; Weak CMI=Lepromatous, many lesions/bacilli, high nerve damage).	Pulmonary Disease! (MAC, kansasii), Lymphadenitis (kids), Skin Infections (marinum, Rapid Growers), Disseminated Disease (AIDS/MAC)Mycobacterium avium Complex (MAC) common cause of lung disease & disseminated disease in AIDS. Other NTM cause diverse infections.
IV. Treatment & Prevention
Treatment	Multi-Drug Therapy (MDT - RIPE)!; Long Duration!; Directly Observed Therapy (DOT)Standard: Rifampin/Isoniazid/Pyrazinamide/Ethambutol for 2 months, then RI for 4 months (sensitive TB). MDR/XDR-TB require longer, complex, toxic regimens. Treating LTBI prevents progression.	Multi-Drug Therapy (MDT)!; Rifampicin + Dapsone (+ Clofazimine for MB); Long DurationBased on paucibacillary (PB: RIF+Dapsone 6mo) vs multibacillary (MB: RIF+Dap+Clofazimine 12mo) WHO guidelines to prevent resistance.	Multi-Drug Therapy!; Species/Susceptibility Dependent!; Very Long Duration!Often difficult. Need specific species ID/drug susceptibility. MAC: Macrolide+Ethambutol+Rifamycin. M. abscessus extremely resistant. Therapy often 12+ months after culture conversion.
Prevention / Control	BCG Vaccine (Childhood); Treat Latent TB!; Infection ControlBCG protects young children from severe disease (variable pulmonary protection). LTBI treatment key. Respiratory isolation for active pulmonary cases.	Early Diagnosis/Treatment; Contact Tracing +/- Prophylaxis?MDT renders patients non-infectious. Single-dose Rifampicin prophylaxis for contacts studied. BCG may offer some cross-protection.	No Vaccine; Avoid Environmental Exposure (Risk Groups); AIDS Prophylaxis (MAC)Prevention difficult. Azithromycin/Clarithromycin prophylaxis for AIDS patients with very low CD4 counts prevents disseminated MAC.

Spirochetes

Category / Feature	Treponema pallidum	Borrelia burgdorferi (Lyme)	Leptospira interrogans
I. Morphology & Motility
Shape / Size / Visibility	Thin, Tightly Coiled; Darkfield!Very slender (0.1-0.2 μm diam) with regular, tight coils. Requires darkfield or immunofluorescence microscopy to visualize live, motile organisms. Gram stains poorly.	Larger Diameter, Wider Coils; StainableWider (0.2-0.5 μm diam) with fewer, irregular coils. Can be seen with Giemsa or Silver stains in blood (relapsing fever Borrelia) or tissue biopsies.	Very Thin, Tight Coils, Hooked Ends!; DarkfieldExtremely thin (0.1 μm diam) with very tight coils. Characteristic bent or hooked ends often seen. Requires darkfield to see motility.
Motility Structure	Endoflagella (Axial Filaments)Periplasmic flagella located between inner and outer membranes cause characteristic corkscrew motion, facilitating tissue invasion.	Endoflagella (Axial Filaments)Similar periplasmic flagella drive motility.	Endoflagella (Axial Filaments)Two periplasmic flagella confer rapid motility and tissue penetration ability.
II. Transmission & Disease
Key Disease	Syphilis (Primary, Secondary, Latent, Tertiary)A multi-stage disease: Primary (chancre), Secondary (rash, systemic), Latent (asymptomatic), Tertiary (cardiovascular, neurosyphilis, gummas). Also Congenital syphilis.	Lyme Disease; (Also Relapsing Fever - other Borrelia spp.)Early localized (Erythema Migrans rash), Early disseminated (cardiac, neuro), Late disseminated (arthritis, chronic neuro).	Leptospirosis; Weil's Disease (Severe Form)Biphasic illness: initial septicemic phase (fever, headache, myalgia), followed by immune phase. Severe form (Weil's) involves jaundice, renal failure, hemorrhage.
Reservoir / Transmission	Humans Only / Direct Contact (Sexual/Congenital)Transmitted through contact with infectious lesions (chancres, rashes).	Zoonosis (Rodents, Deer etc.) / Tick Bite! (Ixodes spp.)Maintained in rodent/deer populations. Transmitted by bite of infected blacklegged ticks.	Zoonosis (Rodents, Livestock etc) / Contaminated Water/Soil! (Animal Urine)Excreted in urine of infected animals, survives in environment. Humans infected via contact with contaminated sources through breaks in skin/mucosa.
III. Culture & Diagnosis
Cultivation	Cannot Be Cultured In Vitro!Obligate human parasite. Relies on animal models (rabbit testes) for propagation.	Difficult! Complex Media (BSK-H); Slow GrowthRequires Barbour-Stoenner-Kelly medium. Microaerophilic. Takes weeks. Culture rarely useful clinically.	Difficult! Special Media (EMJH); Slow GrowthRequires enriched liquid/semi-solid media (Ellinghausen-McCullough-Johnson-Harris). Aerobic. Takes weeks. Culture often insensitive.
Diagnostic Approach	SEROLOGY! (VDRL/RPR Screen + FTA/TPPA Confirm); Darkfield (Early Lesions)Antibody detection mainstay. Non-treponemal tests for screening/activity, treponemal tests for confirmation. Direct visualization possible from active lesions. PCR available but not routine.	Clinical Picture! (EM Rash); SEROLOGY! (2-Tier ELISA/Western Blot - LATE Stage)Erythema Migrans rash is diagnostic if present. Serology unreliable early, use 2-step testing later for confirmation (esp. arthritis/neuro). PCR on CSF/joint fluid possible.	SEROLOGY! (MAT Gold Standard); PCR (Early Stage Blood/CSF); Culture less commonMicroscopic Agglutination Test is reference but complex/requires live antigens. IgM ELISA useful early. PCR useful in first week.
IV. Pathogenesis & Treatment
Pathogenesis	Invasion; Inflammation (Endarteritis); Immune EvasionSlow clearance allows persistence. Vascular damage characteristic of tertiary syphilis. Few outer membrane proteins hinders antibody response.	Motility/Dissemination; Host Inflammatory Response!; Immune ModulationSpreads widely. Inflammation triggered by lipoproteins drives symptoms like arthritis. May alter surface proteins (Osp).	Direct Tissue Invasion; Vascular Damage!; Endotoxin-like Activity?Invades via motility. Damages endothelium causing bleeding. Can trigger severe immune response (cytokine storm?). Renal/hepatic injury common.
Treatment	Penicillin G! (Benzathine form for Early/Latent)Remains drug of choice for all stages. Dosing and duration depend on stage. Doxycycline alternative for allergy.	Doxycycline (Early)!; Amoxicillin (Kids); Ceftriaxone (Severe/Late)Oral antibiotics effective for early stages. IV Ceftriaxone needed for meningitis, carditis, late arthritis.	Doxycycline (Mild)!; Penicillin/Ceftriaxone (Severe)!Early/mild disease treated orally. Severe disease (Weil's) requires IV therapy. Supportive care vital.
Prevention	Safe Sex!; Screening; Partner NotificationCondom use reduces risk. Routine screening (esp. pregnancy). Treat partners.	Tick Avoidance/Removal!; Repellents/PermethrinCheck for ticks after outdoor activity. Use DEET/Picaridin. Treat clothing with permethrin. Landscape management.	Avoid Contaminated Water/Soil; Protective Gear; Animal VaccinationRisk reduction for occupational exposure. Control leptospirosis in livestock/pets.

Cell Wall Deficient Bacteria

Category / Feature	Mycoplasma pneumoniae	Ureaplasma urealyticum / parvum
I. Defining Features
Cell Wall Status	LACKS Peptidoglycan Cell Wall!Cannot be Gram stained. Intrinsically resistant to cell wall active antibiotics (e.g., Penicillins, Cephalosporins).	LACKS Peptidoglycan Cell Wall!Same lack of rigid wall structure. Requires sterols in membrane.
Unique Requirement	Requires Exogenous Sterols (Cholesterol) for MembraneIncorporates host cholesterol into its cell membrane for stability.	Requires Exogenous Sterols AND Urea!Unique metabolic requirement for urea, hydrolyzes it via Urease enzyme.
Size / Morphology	Smallest Free-Living Bacteria!; PleomorphicVery small genome and cell size. Variable shape due to lack of rigid wall. Can pass through some bacterial filters.	Extremely Small ('T-strains'); PleomorphicForms tiny ('T' = tiny) colonies on specific media.
II. Culture & Diagnosis
Culture Needs	VERY Fastidious; Slow (Weeks!); Special Media (SP4); AerobicRequires complex media with sterols, yeast extract, glucose. Needs aerobic conditions. Colonies take weeks.	VERY Fastidious; Needs Urea!; Special Media (A8); Microaerophilic/AnaerobicRequires urea in media, sterols. Grows faster (days) than M. pneumoniae but colonies minute.
Colony Appearance	"Fried Egg" Appearance (Microscopic)Characteristic colony morphology with dense center growing down into agar and lighter periphery on surface.	Tiny Granular ("T-strain") ColoniesVery small colonies, historically referred to as T-strains.
Primary Diagnostic Method	PCR! (Respiratory sample); Serology common (but slow)NAATs highly sensitive/specific. Serology (IgM/IgG) often used but takes time to develop. Culture rarely done clinically.	PCR! (Urogenital sample); Culture difficultNAATs available for detection in GU tract specimens. Culture requires specialized labs.
III. Disease & Pathogenesis
Key Disease Association	Atypical "Walking" Pneumonia; TracheobronchitisMajor cause of community-acquired pneumonia, especially in school-age children and young adults. Often milder course than typical bacterial pneumonia.	Non-Gonococcal Urethritis (NGU); Possible Role in Preterm Birth?Established cause of NGU in men. Role in adverse pregnancy outcomes (chorioamnionitis, preterm labor) debated but biologically plausible. Neonatal infections possible.
Virulence Factors	P1 Adhesin!; H₂O₂ Production; CARDS Toxin?P1 protein crucial for attachment to respiratory cilia causing damage. Oxidative stress contributes. Community Acquired Respiratory Distress Syndrome (CARDS) toxin may play role.	Urease!; Phospholipase A/C?; Adherence?Ammonia from urease may be toxic. Phospholipases could damage host membranes. Mechanisms less well defined.
IV. Treatment & Prevention
Antibiotic Resistance Profile	Intrinsic Resistance to β-Lactams!Cannot use drugs targeting cell wall synthesis.	Intrinsic Resistance to β-Lactams!Same intrinsic resistance.
Effective Drug Classes	Macrolides!; Doxycycline; FluoroquinolonesProtein synthesis inhibitors or DNA gyrase inhibitors are active. Macrolide resistance is increasing.	Macrolides (Azithro); Doxycycline; Fluoroquinolones (Limited role)Susceptibility can vary. Tetracycline resistance reported.
Prevention	None (No Vaccine)General respiratory hygiene helps reduce spread.	None (No Vaccine); Safe Sex Reduces SpreadCondom use can reduce sexual transmission.

Select Bacteria Category

Gram-Positive Cocci

Gram-Negative Cocci

Gram-Positive Rods

Enterobacteriaceae

Other G(-) Rods

Mycobacteria

Spirochetes

Cell Wall Deficient

Gram-Positive Cocci (GPC)

Gram-Negative Cocci (GNC)

Gram-Positive Rods (GPR)

Enterobacteriaceae (Enteric Gram-Negative Rods)

Other Clinically Significant Gram-Negative Rods

Mycobacteria

Spirochetes

Cell Wall Deficient Bacteria