Bacteriology Flashcards
What are mechanisms that bacteria or pathogens use to cause disease?
Invasion - The process of microorganisms entering body tissue or host cells, surviving & spreading in the body. Toxigenicity - Production of microbial toxins that damage the host but aid in microorganism’s survival. Immunopathology - Host’s immune response causes damage to the host itself.
Give an example of a bacteria that uses toxigenicity to cause disease.
Clostridium tetani - Causes tetanus by production of tetanospasmin toxin, which causes muscle spasms. Prevents neurons from releasing inhibitory neurotransmitters GABA & glycine by degrading protein synaptobrevin. Results in FAILED INHIBITION of motor reflexes by sensory stimuli. Gram+ rod, anaerobic, spore-forming, found in soil & faeces.
Give an example of a bacteria that uses invasion to cause disease.
Brucella abortus - Causes Brucellosis in cattle by invading host cells. Gram (-), non-spore-forming, facultatively intracellular.
Give an example of a bacteria that uses immunopathology to cause disease.
Mycobacterium bovis or M. tuberculosis - Causes granulomatous response that damages lung tissue. Gram+ rod, aerobic, non-motile; replicates in alveoli of host.
What is pathogenicity?
The ability of an infectious agent to cause disease.
What is virulence?
The measure of a pathogen’s ability to cause disease; how pathogenic something is.
What is pathogenesis?
The process of disease progression.
What is an opportunistic pathogen?
A pathogen only capable of causing disease when allowed to do so through particular circumstances of the host.
What is a commensal?
A microorganism that naturally resides on the body, causing no harm. In some cases, when immunity in the host is suppressed or compromised or ends up in the wrong area, a commensal can become pathogenic. Eg., E. coli is a commensal of the colon but becomes pathogenic if it gets into the urinary tract. Eg. Staphylococci is a commensal of the skin but can cause infection if skin is broken.
What is nosocomial infection?
Hospital-acquired infection. Eg., Bacteria tend to become more pathogenic in hospitals where a lot of antibiotics are used, resulting in resistant microorganisms.
What are the differences between Gram (+) & Gram (-) bacteria?
The distinction depends on the microorganism’s response to Gram stain with crystal violet. Gram (+) bacteria stain purple because they have a thick peptidoglycan wall that absorbs and reacts with the stain. Gram (-) bacteria stain pink with counterstain because they have outer & inner membranes that sandwich the thin peptidoglycan cell wall, which doesn’t pick up the crystal violet.
What are the main mechanisms employed by Gram+ bacterial exotoxins?
- Digest surroundings / break down host tissue so bacteria can extract needed nutrients for survival and replication. 2. Damage host’s immune system using neurotoxin or biological toxin.
Give some examples of exotoxins that are enzymes.
- Phospholipase 2. Protease 3. Collagenase 4. Hyaluronidase - digests host proteins
Give some examples of Gram+ exotoxins that are neurotoxins/biological toxins and explain how they work.
- Botulinum - produced by Clostridium botulinum; causes botulism. Prevents vesicles in neuromuscular junction from anchoring to neuron cell-membrane to release acetylcholine. Inhibition of Ach release at synapse results in FLACCID PARALYSIS. 2. Tetanus, aka tetanospasmin: produced by C. tetani; prevents affected neurons from releasing inhibitory neurotransmitters GABA & glycine, so muscles respond to just tiny sensory stimuli, tetanic spasms.
Give some examples of exotoxins that damage the host’s immune system.
- Leucocidins: kill white blood cells such as neutrophils, basophils, eosinophils, monocytes, lymphocytes, etc. These are produced by Staphylococcus & Streptococcus spp. 2. Antichemotaxins: Inhibit chemotaxis of neutrophils to site of infection. Eg., Chemotaxis Inhibiting Protein of S. Aureus (CHIPS) 3. C5a Protease: Cleaves potent neutrophil chemotaxin called C5a, which is produced by complement system. C5a peptidase, produced by Streptococcal progenes, is necessary to minimuse influx of neutrophils.
What are endotoxins and what type of bacteria produce them?
They are lipopolysaccharides (LPS) in the bacterial cell’s outer membrane that don’t do damage themselves but ignite host immune response (mainly cytokine response). They are kept “within” the bacteria cell membrane & only released after destruction of the bacteria cell wall, e.g. via detergent. The lipid part of cell membrane is the “endotoxin” & the hydrophilic”polysaccharide O side-chain” makes up the “O-antigen”. Gram (-) bacteria ONLY are associated with endotoxins.
What mechanisms of pathogenicity do Gram (-) bacteria employ?
- Adhesion 2. Exotoxins 3. Endotoxins (lipopolysaccharides) 4. Cell-host interaction 5. Capsular polysaccharide 6. Iron acquisition 7. Evasion of host immune system
How do Gram (-) bacteria use adhesion as a mechanism of pathogenicity?
- Fimbriae, villi-like extensions on cell wall made of pili protein units that act as antigens. Eg., K88 aka F4 help E. Coli stick to mucosal surfaces / enterocytes in colon. P. fimbriae help E. Coli stick to epithelium of urinary tract, causing infection. 2. Filamentous haemagglutinin helps Bordatella bronchisepta to stick to canine ciliated tracheal epithelium, avoiding muco-ciliary escalator. 3. Polar fimbriae help Dichelobacter nodosus to stick to keratinised tissues in hoof of sheep, leading to footrot.
Give examples of exotoxins used by Gram (-) bacteria.
- Cholera toxin - Activates adenylate cyclase; increased level of intracellular cAMP promote secretion of fluid and electrolytes in intestinal epithelium leading to diarrhea 2. Heat-labile LT toxin - released by E. Coli; similar or identical to cholera toxin 3. Heat-stable ST toxin - released by E. Coli; binding of ST enterotoxins to a guanylate cyclase receptor results in an increase in cyclic GMP (cGMP) that adversely effects electrolyte flux. Promotes secretion of water and electrolytes from intestinal epithelium leading to diarrhea 4. Shiga-like toxin - released by E. coli; cleaves rRNA resulting in inhibition of protein synthesis in susceptible cells. Results in diarrhea & hemorrhagic colitis. 5. Osteolytic toxin of Pasteurella multocida 6. Leucotoxin of Mycobacterium haemolytic 7. Exotoxin A of Pseudomonas aeruginosa 8. Keratinase of Dichelobacter nodosus
What is meant by cell-host interaction employed by Gram (-) bacteria?
Bacteria that are either commensal and/or opportunistic.
What is a Gram (-) bacteria’s capsular polysaccaride (capsule) and how does it work?
A thick, mucous-like, layer of polysaccharide. This “capsule” cloaks antigenic proteins on the bacterial surface that would otherwise provoke an immune response - phagocytosis by neutrophils and opsonophagocytosis by macrophages – & thereby lead to the destruction of the bacteria. Capsular polysaccharides are water soluble, commonly acidic & linear.
What is LPS and what role does Lipid A play in LPS’s role as Gram (-) endotoxin?
LPS is a three-part structure in Gram (-) outer membrane. The innermost, hydrophobic portion is Lipid A, which anchors the LPS molecule, comprised of Lipid A, core polysaccharide & O-side chains, aka O-antigen, to the outer membrane. When released from the bacterial cell well, Lipid A activates macrophages and causes IL-1 & TNFalpha release, stimulating a strong immune response. Clinically, the response can range from fever, thrombosis, DIC, leucopenia to complement, hypotension, circulatory collapse, shock & death.
How does iron acquisition aid in a Gram (-) bacteria’s pathogenicity?
Since no bacteria can synthesize iron, Gram (-) bacteria scavenge or harvest it to grow using: 1. Siderophores: High-affinity chelating compounds put out by Gram (-) bacteria into environment that scavenge iron & bring back. 2. Transferrin-binding protiens - Proteins that hold iron, like Hb, that bacteria can clutch onto & steal from. Eg. S. aureus possess transferrin-binding proteins in cell wall.
What are three ways in which the cell membrane & capsule of the Gram (-) bacteria help the pathogen evade the host immune system?
- Evade phagocytosis by innate immune system: use hydrophilic capsule or LPS outer membrane; 2. Resist complement & lysozyme: same non-stabilising capsule & LPS helps avoid opsonisation with C3b (alternative pathway); 3. Use of molecular mimicry to avoid antibody-mediated opsonophagocytosis ie., host recognises surface components as “self antigens”, thus no antibody not produced. Eg., K1 antigen (sialic acid) of E. coli, hyaluronic-acid capsule of beta-haemolytic streptococci & K5 antigen (desulfoheparin) of E. coli.
What are some diseases caused by bacterial use of adhesion, ie., fimbriae or filamentous haemagglutinin?
Kennel cough (Bordatella bronchisepta) Pink Eye / New Forest Eye (Moraxella bovis) Diarrhoea (E. coli) Footrot (Dichelobacter nodosus)
How do obligate & facultative intracellular pathogens hide from the host’s immune defences?
- Inhibit phagosome & lysosome fusion (evading macrophages); 2. Lyse phagosomal membranes to escape into cytoplasm 3. Resist killing by lysosomal killing mechanisms
Which of the following are extracellular pathogens? More than one. A. Escherichia coli B. Chlamydia C. Rickettsia D. Streptococci
A & D Chlamydia & Rickettsia are obligate intracelluar bacteria.
Salmonella, Listeria, Mycobacterium and Brucella are: A. Extracellular pathogens B. Obligate intracellular pathogens C. Facultative intracellular pathogens D. None of the above
C
Fimbriae that bind mannose are non-pathogenic except for assisting in bladder colonisation & infection. True or False?
True. Mannose sugar binds to fimbriae, thus blocking it from binding to enterocytes. But mannose-resistant fimbriae, such as K88 aka F4 on E. coli are highly pathogenic.
Which type of bacteria, Gram (+) or Gram (-), staphylococci or bacilli, can form spores?
Gram (+) bacilli only.
What are the two main genera of Gram (+) bacilli?
Bacillus and Clostridium
Describe Clostridium bacteria.
- Gram (+) bacilli - Spore-forming - Anaerobic - Found in faeces-contaminated soil & sewage - Cause tissue-invading (histotoxic) and enterotoxic syndromes in sheep especially, controlled by toxoid vaccines - Cause botulism & tetanus using neurotoxins - Clostridium perfringens - five types - cause serious enterotoxaemias.
What is special about Clostridium perfringens?
It produces many exotoxins that cause enterotoxaemias in various species, especially ruminants. FIVE TYPES (A-E), all producing alpha-toxin. Type A: Mostly alpha. Causes enteritis in pigs & chickens, gas gangrene in humans. Type B: Mostly beta, some epsilon. Causes LAMB DYSENTERY. Type C: Mainly beta. STRUCK & Necrotic enteritis in lambs & piglets. Type D: Mainly epsilon. PULPY KIDNEY in sheep. TYPE E: Mostly iota, less important. C. perfringens also causes histotoxic infections in which spores germinate in contaminated tissue, which becomes anaerobic, enabling secondary infection.
What is LAMB DYSENTERY & how is it caused?
Enterotoxaemia in sheep caused by Type B Clostridium perfringens (mostly beta toxin, some epsilon), prevalent in Scotland & N. England. Lambs < 2 mo suckle from infected ewe, overgrowth of toxin absorbed, die.
What is STRUCK & how is it caused?
Sheep enterotoxaemia caused by Type C Clostridium perfringens (mostly beta toxin), prevalent all over England. Sheep overeat, β-toxin not INactivated by trypsin because maybe there’s a pancreatic deficiency in the sheep, toxin damages mucosa, absorbed, major organ failure.
What is PULPY KIDNEY & how is it caused?
Sheep enterotoxaemia caused by Type D Clostridium perfringens (mostly epsilon toxin). Lambs transferred from rough pasture onto richer diet, poss. with concentrate, suddenly have overgrowth of bacteria, ε-toxin activated by enzymes, ↑ permeability of small intestine, absorption, ε-toxin affects brain & kidney ↑ capillary permeability, ↑ intracranial pressure, CNS affected. At PM, kidney shows autolytic changes.
How do spores, formed by Gram (+) bacilli, survive in the face of adversity?
They are resistant to: - dessication - cold & freezing - boiling - radiation - UV light - chemicals such as detergents & disinfectants
Name two types of anaerobic, spore-forming, Gram (+) bacteria that release neurological toxins.
Clostridium tetani & Clostridium botulinum
Name an aerobic, spore-forming, Gram (+) bacteria that uses its polysaccharide capsule & toxins to cause death.
Bacillus anthracis -> anthrax
What is the pathogenesis of Bacillus anthracis, which causes anthrax?
Spores in contaminated soil are ingested by mainly ruminants (and also horses) → phagocytosed by neutrophils, eosinophils, macrophages, etc. → germinate in the lymphatics → spread to bloodstream → multiply → septicaemia
How does the bacterial capsule aid in the virulence of Bacillus anthracis?
The poly-γ-D-glutamic acid (PGA) capsule disguises B. anthracis from immune surveillance by preventing C3b (complement) from binding to the surface (thus it’s anti-phagocytic) and allows its unimpeded growth in the host. The capsule stains mauve/pink with polychrome methylene blue stain.
How does the exotoxin aid in the virulence of Bacillus anthracis?
Toxin contains three components that become progressively more toxic as they come together, the most lethal being the triple combination called Holotoxin. When Factor I (oedema factor), Factor II (protective factor) & Factor III (lethal factor) come together, the holotoxin inhibits phagocytosis, becomes toxic to macrophages, causes pulmonary oedema, shock and death.
What is Blackleg or Blackquarter & what causes it?
It’s a histotoxic infection in cattle caused by Clostridium chauvoei. Spores lie dormaon in muscle until activated by trauma, which lowers redox of tissues (lower oxygen tension); anaerobic environment leads to outbreak. Runs down fascia, darkish purple, gaseous tissue.
What are the three types of clostridial diseases?
- Enterotoxaemia eg. Lamb dysentery caused by C. perfringes 2. Histotoxic infection eg. Blackleg caused by C. chauvoei 3. Intoxication eg. Botulism caused by C. botulinum; ingestion of pre-formed toxin
How can clostridial diseases be treated?
- Clostridial toxoids - deactivated toxin treated with formalin, retain antigenicity but loses toxicity. Eg. Tetanus vaccine, Heptavac for sheep 2. Antiserum for immediate treatment - passive protection from antibody purified from horses; has antibodies in it so doesn’t stimulate immune system; faster than vaccine
How can bacillus diseases be treated?
- Sterne spore vaccine - live, avirulent (non-capulated) strain of B. anthracis (anthrax is notifiable - report to DEFRA)
All Gram (+) bacteria are capable of forming spores. True or false?
False. Only Clostridia & Bacilli, which are Gram (+) bacilli, can form spores. Other Gram (+) bacilli don’t form spores. These include: Listeria Corynebacterium Erysipelothrix Rhodococcus Arcanobacterium Actinomyces Nocardia Dermatiphilus Mycobacterium Gram (+) cocci also don’t form spores.
Can all Gram (+) bacteria be divided into acid-fast and non-acid-fast?
No. Only non-spore-forming Gram (+) bacilli can be divided into acid-fast and non-acid fast. Only Mycobacterium species, eg. M. bovis, M. tuberculosis & M. paratuberculosis, are classified as acid-fast. This means they carry a waxy layer on their surface that’s resistant to many chemicals & don’t let stains in. They must be stained with Ziehl-Neelsen, which reacts with mycolic acid in cell wall to stain red. Non-acid-fast stains blue.
Which Gram (+) bacteria is acid-fast?
Mycobacteria spp. including: M. bovis (bovine TB) M. tuberculosis (human TB) M. paratuberculosis (Johnes disease, ruminants) M. avian (avian TB) Mycobacterium is a Gram (+) bacillus, non-spore-forming, acid-fast.
Name four Gram (+) bacillus bacteria that are NOT acid-fast.
- Listeria 2. Erysipelothrix 3. Actinomyces 4. Arcanobacterium Others include Corynebacterium & Rhodococcus
Name five Gram (+) bacilli that are commensal or opportunistic, and name the diseases they cause.
- Erysipelothrix: Erysipelas in pigs. - Arcanobacterium (Trueperella); Summer mastitis aka “dry cow mastitis”; ovine foot disease - Actinomyces: Lumpy jaw in sheep & cattle (A. bovis); Actinomycosis in dogs; Canine thoracic lesions (A. viscosus) - Corynebacterium: Cystitis, UTI, kidney abscesses - Rhodococcus equi: Chronic suppurative bronchopneumonia in foals
What is Erysipelothrix?
Gram (+) bacilli, non-spore-forming, non-acid-fast commensal bacteria that resides in lymphoid tissue of pigs (also found in turkeys, fish & reptiles). Its capsule resists phagocytosis by white blood cells & it produces neuraminadase toxic enzyme that penetrates & damages tissue. Causes systemic bacterial infection by invading lymphatics; septicaemia results in acute cases. Endocarditis & arthritis in chronic infection in pigs. Characterised by diamond-shaped lesions on skin due to dermal ischaemic infarction. Zoonosis in fish & meat workers = Erysipeloid
What is Arcanobacterium?
Also known as Trueperella, it’s a non-motile, small, opportunistic Gram (+) bacilli that resides in the nasopharynx of ruminants, URT & genital tracts of domestic animals & the ruminal wall of cattle. It can cause a wide variety of suppurative infections in farm animals, & is the commonest cause of wounds & abscesses. Causes summer mastitis aka “dry cow mastitis”. Uses haemolysin, proteases, DNase, neurominadase. Important species: A. pyogenes
What is Actinomyces?
It’s a Gram (+) bacilli, non-acid-fast, FACULTATIVE AEROBE (prefers anaerobic), opportunistic & non-motile, normally reside in oral cavity of cattle. Filamentous & branching under micro. Inoculated into tissues by trauma such as barbed wire, it may set up granulomatous lesions in soft tissue & bone. A. viscosus -> canine thoracic lesions, actinomycosis A. bovis -> lumpy jaw (actinobacillosis) in ruminants
What is Corynebacterium?
Gram (+) bacillus, non-acid-fast, usually commensal, non-motile, found in skin & mucous membrane of animals & humans. In cattle it can cause cystitis, UTI & kidney abscesses. Transmitted via infected urine, sexual contact; adheres to urinary tract using fimbriae & produce potent urease enzyme.
What is Corynebacterium pseudo-tuberculosis?
Like other Corynebacterium species, it is found in skin of ruminants. Microscopically, it resembles “Chinese letters”. Unlike other Corynebacterium species, it is facultatively intracellular, and forms nodules that rupture & spread. It uses phospholipase as exotoxin, and causes caseous lymphadenitis in sheep & goats from shearing wounds; and ulcertiave lymphangitis in horses.
What is Rhodococcus?
Gram (+) bacilli, short rods, non-motile, can survive intracellularly & persists in contaminated soil for years. Its natural habitat is the soil and intestines of horses. It can cause chronic suppurative bronchopneumonia in foals (adults are immune), characterised by large pulmonary abscesses.
What is Mycobacterium?
Gram (+) bacillus, round-ended, aerobic, non-spore-forming, non-filamentous, non-branching, some pathogenic. Cause bovine TB, Johnes Disease, avian TB, leprosy (M. leprae) Pathogenesis: Inhalation/ingestion→uptake by macrophages & survival in macrophages → migration to lymph nodes → formation of granulomas → delayed (type IV) hypersensitivity & cell-mediated immune response (destructive to tissues). Transmitted via respiratory route in cattle >6 mo, via alimentary tract in post-natal calves, and congenital route Important species: M. bovis, M. paratuberculosis, M. avium
Name some PATHOGENIC, Gram (+) bacilli bacteria that are non-spore-forming.
- Mycobacterium tuberculosis, M. bovis, M. paratuberculosis. - Nocardia - Dermatophilus congolensis - Listeria monocytogenes, L. ivanovii
What is Listeria?
Gram (+) bacillus, motile, survives intracellularly in epithelial cells by lysing the phagosome that endocytoses it inside the cell, using listeriolysin. Can grow at low temperature (eg in fridge), 4C-45C, pH 5-9. Usually saprophytic; healthy ruminants can be carriers that shed it in milk & faeces. Causes septicaemia, mastitis, meningocephalitis, abortion & CNS disease in cattle & sheep (Listeriosis). Zoonotic in young & elderly who ingest contaminated meat or milk. Pathogenic: L. monocytogenes - found in silage from sheep faeces in cut pasture L. ivanovii
What is Dermatophilus congelensis?
Gram (+) bacillus, pathogenic, non-spore-forming. It’s in the actinomycete group so it microscopically resembles filaments, but also has life cycle that includes longitudinal & transverse division & a motile coccoid form that spreads the infection across the skin. Releases adenase & lectinase. Causes Mud Fever (streptothricosis) aka rain scald in horses; pyogenic.
What is Nocardia?
Gram (+) bacillus soil bacterium, non-spore-forming, non-motile, branching, short filamentous. Semi-acid-fast (contains mycolic acid). Often in oral flora. Infection by wound or inhalation, causes chronic, progressive disease: Causes granulomatous lesions because it can survive & grow in macrophages. Nodules form, rupture & spread. Resistant to penicillins that would kill Actinomyces. Important species: N. asteroides
What are two Gram (+) bacillus, non-spore-forming MOTILE bacteria?
- Listeria - tumbling motility at 18C 2. Dermatophilus congolensis - motile in its coccoid form
What is bovine tuberculosis & what causes it?
Caused by Mycobacterium bovis, a Gram (+), non-spore-forming, non-motile, acid-fast, strictly aerobic bacteria. It’s inhaled by cattle over 6 mo (nasal secretions) or ingested from pasture. It survives phagocytosis by macrophages & migrates to lymph nodes, where it causes granulomas, delayed hypersensitivity & destruction of tissues by T-cell response. It changes the cytokine response to favour spread of disease. It’s chronic progressive, fatal wasting disease. Shed from respiratory tract & udder by “open case” carriers. It’s resistant to drying and antibiotics.
