BIOL 2421 Microbiology Lecture Notes: Cocci Bacterial Diseases Dr. Weis
Gram Positive cocci are grouped together based on their gram stain reactions, thick cell wall composition, and spherical shape. Most of the organisms in these groups are members of the Micrococcaceae family.
MICROCOCCUS
G+ cocci in pairs or clusters
Aerobic
Colonies may be red or yellow in broth or on Nutrient/TSA agar plate
Location:
Soil
Water
Skin contaminant
Common species
M. luteus
M. roseus
M. varians
Id: color of colonies on nutrient agar
Growth on MSA
Catalase +
Saphrophytic, harmless, unless immunocompromised patients
Could cause UTI, pneumonia, septic shock
STAPHYLOCOCCUS
Most important species in Micrococcaceae family.
Classified into two groups: Aureus and non-aureus species
28 species and 4 subspecies
G+ cocci in clusters
Nonmotile
Facultative anaerobe
Catalase +
Grow in >7.5% NaCl
Ubiquitous: normal flora for skin, mouth, nose, throat
30% in anterior nares are pathogenic
20% on skin are pathogenic
Predisoposing factors to Staph infection
a) Immune: infants, pregnant mothers, burn patients, steroids, chemotx
b) Concurrent disease: CF, emphysema, leukemia, Neoplasia, F.B, DM
c) Antibiotic resistance
Major diseases:
Skin
Systemic: bacteremia, bone, pneumonia
Other: Toxin mediated
(enterotoxins) produced in stationary phase of growth
Staphylococcus aureus
Most virulent species of group
Most strains have several AB resistances (MRSA, VRSA)
DX: regular Staph tests (MSA, DNase, coagulase, catalase)
β- hemolysis on BAP
Ferment mannitol
Coagulase +
TX: Susceptible Antibiotics [Vancomycin, Cephalosporins, TMPS]
Prevention: aseptic precautions
Transmission: direct
Diseases:
* Skin and Soft Tissue
~ folliculitis
~ furuncles, carbuncles
~ impetigo
~ wound infection: postoperative
* Endovascular
~ endocarditits: IV drug users, prosthetic heart valves
* Bacteremia : catheter, Foreign body, burn
* Bone Infection
~ osteomyelitis
~ septic arthritis
* Respiratory Tract Infection
~ pneumonia
~ empyema
* Intoxications
~ TSS: exotoxinà sloughing (GI, skin)
~ Food poisoning: enterotoxin [exotoxin]
Virulence Factors
* Cell wall: Peptidoglycan, Teichoic acid, Protein A
* Clumping Factors
* Adhesions
* Exotoxins: membrane disrupting toxins (protein channels)
^ Hemolysins (α toxin): lysis of RBC à anemia
^ Enterotoxin: causes secretion large amounts of fluids
^ TSST: induces IL-1à inflammation, desquamation
^ Exfoliatinsàsloughing of skin
^ Leukocidin: destroys WBCsà leukopenia
* Extracellular Enzymes
^ coagulaseà conversion of fibrinogen to fibrinà clot
^ catalaseà converts H2O2 to H2O and O2
^ fibrinolysinàplasminogen to plasmin
^ nuclease
^ lipaseàpenetrates fatty tissue à abscess
^ protease
Staphylococcus epidermidis
DX: regular Staph tests
Coagulase (–)
TX: Sensitive AB [Vancomycin]
Diseases
Endocarditis
“Foreign Body”: catheter, prosthetic joint infections
Virulence Factors
Biofilm slime
Staphylococcus saprophyticus
DX: regular Staph tests
Coagulase (–)
TX: Sensitive AB [Vancomycin]
Diseases:
UTI,
usually in younger women
Staphylococcus intermedius
Primary animal bacteria, part of normal oral cavity flora
Recent documentations of zoonotic potential (contact, bite wounds)
Some subspecies can produce enterotoxins, important in food contamination
DX: regular Staph tests
Some subspecies found to be coagulase +
TX: based on Antibiotic sensitivity
Diseases:
Pyoderma (skin affected in animals)
Food
poisoning
Staph summary
S. aureus, capitis, epidermidis, haemolyticus, hominis, saprophyticus, warneri, and xylosis inhabit humans.
S. capitis, epidermidis, saprophyticus, xylosis are opportunistic human pathogens.
S.intermedius has potential for zoonotic disease.
STREPTOCOCCUS
G+ cocci that divides in single plain to form chains
Classified based on haptan C substance carbohydrates in cell wall à
Lancefield Groups
Circular translucent pinpoint colonies
Normal flora: skin, throat, body cavity openings (resp, gi, urinary)
Catalase (-)
Anaerobic
Group A Strep
Streptococcus pyogenes
Opportunistic pathogen
Most virulent species for humans
β hemolytic
nonmotile
Diseases
Respiratory
* Pharyngitis: 90% of all cases [a.k.a. Strep throat]
* Otitis Media
* Scarlet Fever: erythrogenic toxinàrashàdesquamation
Cutaneous
* Pyoderma [Impetigo]
* Erysipelas
* Dermatitis
* Cellulitis
* Necrotizing fasciitis
Other
* STSS [Streptococcal Toxic Shock Syndrome]: pyrogenic
Complicating Infections
* Rheumatic Fever
* Acute Poststreptococcal
* Glomerulonephritis
Virulence Factors
~ Cell wall- M protein = resist phagocytosis by degrading C3B
~ Adhesins
~ Invasins
~ Streptolysin S: nonimmunogenic, O2 stable
~ Steptolysin O: immunogenic, O2 labile [sensitive]
~ Capsule
~ Erythrogenic toxinà rash
~ Protease: cleaves complement protein C5a
Transmission:
Direct
Respiratory
Droplets
Streptococcal Infections can be divided into 3 groups
a) Carrier state
b) Acute Infection
c) Delayed, non-suppurative [asymptomatic infections]
Infection spreads through the affected tissue
and along lymphatic channels to L.N.
Group B Strep
Streptococcus agalactiae
β hemolytic
non-motile
facultative anaerobe
catalase negative
CAMP factor [substance] that works with Staph aureus B-hemolysins
Located in vaginal mucosa
DX: CAMP test
Diseases:
Neonatal: bacteremia, meningitis, pneumonia
Soft tissue infections: pneumonia, arthritis, UTI
STD: vaginitis à vertical transmission
Virulence Factors
Capsule
Adhesins: fibrinogen binding proteins
Hemolysins
CAMP factor
Protease: C5a
Transmission:
Direct
Group C, F and G Strep
β hemolytic
nonmotile
Facultative anaerobe
Catalase (-)
Streptococcus equisimilis (Group C)
Streptococcus anginosus (Group F)
Streptococcus zooepidemicus (Group G)
Disease: Same as Strep. Pyogenes
Skin, respiratory, kidney
Sepsis
Virulence
factor: streptokinase
Group D Strep
Enterococci: E. faecalis, E. durans, E. faecium
Non-enterococci: S. bovis, S. equines
α or δ hemolysis
DX: bile esculin (+ for hydrolysis)
MSA growth
EMB growth
Primarily found in the GI tract
Diseases:
Urinary tract infection
Septicemia: wounds and soft tissue
Cellulitis
Endocarditis
Appendicitis
Virulence Factors:
Adhesins: Aggregation substance, Enterococcal protein
Exotoxins: Cytolysins, Gelatinase
Viridans Group (Lancefield K, H, N)
Streptococcus mutans
Streptococcus mitis
Streptococcus salivarius
Streptococcus oralis
Streptococcus mitior
Streptococcus milleri: S. constellatus, S. intermedius, S. anginosus
α [can be δ ] hemolysis
colonize the oral cavity
Diseases:
Tooth decay [S. mutans]
Subacute Endocarditis
Localized abscesses [S. milleri group]
Virulence
factors: no traditional Strep virulence factors
Streptococcus pneumoniae
Surface CH2O does not correspond to Lancefield groups
Organism was called Diplococcus pneumoniae
Diplococcus in short chains with pointed ends
Capsule: large, thick
α hemolysis
aerobic or anaerobic
Causes purulent exudate (pus or pyogenic)
Diseases:
Pneumonia with blood tinged sputum: lobar-, broncho-
Fever, shaking, chills, pleurisy
Meningitis in children: brain damage, blindness, hearing loss
Sinusitis in children
Otitis media [50% of all cases] in children
On occasion can cause: bacteremia, endocarditis, arthritis, peritonitis
Virulence factors
Capsule: Developed vaccine based on capsular antigens
Hyaluronase
Autolysins
Neuraminidase
Pneumolysin
Secretory IgA protease
DX: gram stain of sputum, bacteria in pairs or short chains
culture
Optochin sensitivity
Capsular Antigen in body fluids
Transmission: Respiratory droplets
TX: AB [penicillin, unless resistant; cephalosporins, erythromycin, quinolones]
GRAM POSITIVE BACILLUS
Erysipelotrhix
E. rhusiopathiae
G (+) bacillus
Nonmotile
Nonspore former
Capsule
Microaerophilic
Saprophyte (world wide distribution)
Human infection à occupational [animal handling]
Exposure: penetrating wound involving animal matter
Disease: indurated macopapular rash, demarcated swelling
Self limiting, although may be temporarily disabling
May cause arthritis or endocarditis in susceptible individuals
Dx: culture of exudate, PCR
TX: AB [penicillins, cephalosporins]
Listeria
L. monocytogenes
L. ivanovii
L. seeligeria
G (+) bacillus
Non capsule, non spore
Motile
Facultative anaerobe
Environmental in soil and gut in non human mammals
Transmission: Direct contact, contaminated diary, vegetables
Vertical
Disease in Humans: Bacteremia
Dermatitis
Meningitis, encephalitis, ophthalmitis
Endometritis
DX: IgG
TX: AB [penicillin, erythromycin]
BACILLACAE : Bacillus and Clostridia
Bacillus cereus group that are human pathogens:
B. anthracis
B. cereus
Bacillus anthracis [anthrax is Greek for coal]
G(+) bacillus
Facultative anaerobe
Endemic in herbivores [goats, sheep, cattle, horses, hippos, elephants, buffalo]
Encapsulated
Spore former: spherical / ellipsoidal endospores; central or terminal; very resistant
Nonmotile
Catalase (+), VP (+), Nitrate Reduction (+), casein hydrolysis
Following entry of organism in the body, the spores germinate inside macrophages and the bacteria are transported to regional L.N. Incubation occurs in 3-5 days while bacteria multiply and produce toxins and protective antigen that binds to target cells and facilitates the entry of the edema / lethal toxin. Lethal toxin triggers the massive release of cytokines from macrophages, thus causing the sudden death common in anthrax infections. Virulence factors are located on 2 plasmids.
Diseases:
Cutaneous anthrax
Most common form of human infections, ~ 95%
Contaminated materials introduced into the skin à2-7 day incubation
Erythemic papule/pustuleàvesiculationà central ulcerationà
Serosanguinous exudationà black eschar
Inhalation anthrax
Symptoms resemble influenzaà respiratory distress
Hemorrhagic necrosis: LN, Brain
Cyanosis,
Shock, coma, death <24 hours
Gastroentestinal anthrax
Contaminated food
Fever à N/V/Dà bowel necrosisàshock àdeath
Virulence Factors
* capsule [polyglutamic acid]: inhibits phagocytosis
* Anthrax exotoxin [edema and lethal factor]
* Protective antigen
DX: organism isolation, PCR
TX: AB [penicillin, quinalones]
Prevention: limit exposure, Vaccine
available for at risk individuals
Bacillus cereus
G (+) rod
Motile: petrichous flagella
nonencapsulated
Aerobic to Facultative Anaerobe
Sporeformer: spherical / ellipsoidal; central or subterminal endospores
Catalase (+), ferments CH2O with no gas, VP (+), Nitrate Reduction (+)
Hydrolyse casein and starch
Diseases:
* Food poisoning [rice, pasta, dairy]
gastroenteritis: ingestion of spores (heat labile)à Diarrhea
intoxication: ingestion of toxins (heat stable) à Vomiting
* Catheter sepsis
* Ocular infections
Virulence Factors
Enterotoxins: heat labile, heat stable
Enterotoxin T, Enterotoxin FM, cytotoxin K, Emetic toxin
Hemolysins
Phospholipase C [lecithinase]
Tx: Supportive for food poisoning
AB for ocular infections
Clostridia
G(+) rod
Obligate Anaerobes
Motile: petrichous flagella
Psychotrophic – Mesophile – Thermophile
Ferments organic matter to create acids, alcohols, CO2
Sacchrolytic or Proteolytic or both
Spore former: distal; spherical / ellipsoidal
Spores can be found years later in soil and animal feces
Produces various exotoxins: tissue destructive and neural
Found in soil, vegetation, GI tract [colon] of mammals
Become pathogenic
in low O2, high lactate, low pH
Clostridium tetani
Acute infections due to exotoxin called tetanospasmin [A-B neurotoxin] in susceptible individuals such as: burn patients, elderly, Sx post op, IV drug users, postpartum [uterus, umbilical cord]. Toxin enters via blood or at peripheral motor nerves to CNS. Tetanospasmin binds to ganglioside membranes of nerve synapses, blocking the release of inhibitory neurotransmitters, thereby causing a generalized tonic spasticity with intermittent tonic convulsions. Once toxin is fixed @ neuron, it can not be neutralized. Proteolytic.
Localized: spasticity of muscle group near wound, without trismus
Cephalic: involves all cranial nerves, seen in children associated with OM
Generalized: described above
Incubation: 5-10 days
Symptoms: jaw stiffness à inability to open jaw (trismus) à tonic spasms
Stiff neck, headache, fever, sore throat, chills
Muscles fixed (facial muscles pulled back), rigid, spasms
Ultimately affects diaphragm à cyanosisàasphyxia
DX: history, muscle spasms
PX: 50% mortality
TX: supportiveà control muscle spasms, maintain airway
Neutralize unbound toxin: IgG (antiserum)--> "Antitoxin"
Tetanus Toxoid
AB
Prevention: immunization
Clostridia perfringens
Membrane disrupting toxin (Type II)à disrupts plasma membrane phospholipids
Sacchrolytic and Proteolytic
Diseases:
Gas gangrene
Uterus and ovarian tubes
Lecithinase exotoxin à RBC to cause hemolysisà renal failure
Myonecrosisà spreads along fascial plane, crepitation, gas production
Food poisoning
Due to meats contaminated by intestinal contents
Symptoms appear 8-12 hours after digestion
Abdominal pain, diarrhea
due to necrotizing enteritis
Clostridia botulinum
types A,B, E cause diseases in humans
Normal flora in the Large Intestine in humans and animals
Sacchrolytic and proteolytic
Spores enter anaerobic environment of canned goods, organism produces toxin
Exotoxin: Botulinum toxin [heat labile] type A-B neurotoxin
Toxin inhibits the release of ACH @ NMJ
* affects muscles of mastication
* affects muscles of limbs
* affects respiratory muscles: intercostals, diaphragm
Toxin type A
Most virulent, mortality is 70%
Most heat resistant
Found in Western U.S.
Organism is proteolytic: breakdown proteins
Toxin type B
Found in Eastern US and in Europe
Mortality is 25%
Proteolytic and nonproteolytic organisms
Toxin type E
Found in marine environments
Outbreaks involve seafood (Pacific NW, Great Lakes)
Nonproteolytic
Less heat resistant, destroyed by boiling
Organism can live in cooler temperatures and is less anaerobic
Other toxin types
C1, C2, D, G, F
C1 and D are bacteriophage induced
DX: ID toxin via antitoxin neutralization reaction
Use: Botox
NOTE:
C. botulinum can also be classified into various groups based on rod shape (straight vs. curved, the toxin produced, fermentation reactions and by products such as H2S and exoenzymes such as lipase, urease)
Group I : curved rod. Toxin A, B, or F, produce H2S and lipase
Group II: straight rod. Toxin B, E, or F; produce H2S, lipase, urease, indole
Group III: straight rod. Toxin C1, C2, or D. only produce lipase
Group IV: straight rod. G toxin. No fermentation, use citrate. Produce H2S only
Pathogens can be classified as
* Intestinal infections
ingesting toxin produced by organism in poorly prepared food
* Extra-intestinal
: wound botulism
Clostridia difficile
Toxins
* Enterotoxin
* Cytotoxin
Nosocomial diarrhea:
direct transmission,
30% of Nosocomial diarrheas
semi-formed stool
Antibiotic associated / induced colitis
Other “G (+)” rods that are actually Acid Fast
Actinomyces
“G (+) “ rod, branching
weakly acid fast
Mycolic acid in cell wall
Anaerobic
Oral cavity commensals: lives in crevices around teeth
Proprionobacterium
Actinomycoses israelii
Location:
Lumpy jaw (cervicofacial): swelling
Thoracic (Pulmonary form): chest pain, cough, fever
Abdominal form (Cecum, appendix, peritoneum): V/D
Pelvic form (vagina): discharge
Generalized: spreads hematogenously
Skinà brainà liverà kidney
Disease
Small communicating abscesses
Purulent discharge with sulfur granules
Tissue induration and avascular fibrosis
DX: ID organism
Sulfur granules
TX: AB [Penicillin, tetracycline, erythromycin]
Drain
abscesses
Nocardia
Sometimes classified in the Mycobacteriaceae family
N. asteroides
G(+) rod, filamentous, branching
Weakly acid fast [less mycolic acid in cell wall, moderate length chain]
Soil saprophyte, worldwide
Human systems affected: respiratory, sometimes GI & Skin
Seen in susceptible individuals: HIV, organ transplant
Diseases:
* respiratory infections that resemble TB infections
* abscesses: skin, brain, kidney
DX: ID organism in culture
TX: AB [TMPS], if not treated = fatal
MYCOBACTERIACEAE
“G(+)” rod à Acid Fast [long chains of mycoloic acids in cell wall]
non sporeformer
non motile, but will have branching growth of slightly curved rods
Aerobic
Catalase (+)
Slow growers = disease producing,
Fast growers= nonpathogenic
Disease TB
Caused by Mycobacterium tuberculosis, M. bovis, M. africanum
Respiratory droplet transmission
Slow growers, therefore, pathogenic
Mycobacterium tuberculosis
Disease
Pulmonary TB: Caseous necrosis, nodular scars
Disseminated TB: clinical TB in any organ such as
L.N., brain, kidney, bone, skin, abdominal organs
Organism is phagocytized but not killed. Creates calcified nodule
Increase in incidence, especially immunocompromised, IV drug users
Disease stages:
a) primary (initial) : any age, clinical TB in any organb) latent (dormant)c) Recrudescent (reactivates and spreads): immuncompromised
Disease Classifications:
1) Pulmonary TB2) Extra Pulmonary TB: any other organ besides lung
a. Genitourinary TB:
i. kidney, destroys parenchyma
ii. salpingo-oophoritis: sterility due to scarring
b. Tuberculous Meningitis: subarachnoid spacec. Miliary TB: bone marrow, causes blood dyschrasiad. Tuberculosis Peritonitis: from abdominal LNe. Tuberculosis Pericarditis: from mediastinal LNf. Tubuerculosis Lymphadenitis: from lung to hilar LNg. Tuberculosis of Bones and Joints: vertebra, long bonesh. Gastroinestinal TB: after prolonged exposure, high loadi. Tuberculosis of the Liver and Gall bladder: advanced dz
DDX: Other pulmonary diseases, lymphadenitis, cutaneous granulomas
Caused by other Mycplasmas (avium, fortuitum, kansasii)
Virulence Factors
~ mycolic acid wax in cell wall
~ mycobactin : Iron chelator
~ catalase
DX: organism in specimen (sputum, lavage fluids, CSF, urine, peritoneum)
Culture on special media
Chest X-rays
Tuberculin skin test (screen)
TX: AB [Isoniazid which blocks mycolic acid synthesis AND Rifampin]
Vaccine made
from attenuated strain of M. bovis,
will cause (+) skin test reaction. Used
only in developing countries with high prevalence for TB. Not
used in US, no conclusive efficacy.
Mycobacterium leprae
Obligate intercellular parasite
Worldwide, most cases in Asia, Africa, South-Central America
Reservoir: Humans, Armadillos, soil
Contact: Direct, nasal droplets, possible vector transmission
Incubation: 5-7 years, slow growing
Disease: Leprosy
Types
Tuberculoid Leprosy
Nonpuritic rash with few macules/ plaques with raised borders
Possible damage to peripheral nerves
Lepromatous Leprosy
Skin nodules/plaquesà erythema nodosum
Distal peripheral neuropathy/neuritisà somatic sensory
Loss of skin appendages: body hair, eyelashes, eyebrows
Ulcerations that become secondarily infected àbacteremia
Other areas:
Nasal mucosa and cartilage: congestion, perforation
Testicular Atrophy: Impotence
Renal failure due to amyloidosis
Borderline Leprosy
Can
develop into lepromatous or reverse to tuberculoid
Virulence Factors: same as M. tuberculosis
* high lipid content of wall: mycolic acid, Wax D
* Iron chelation
* Catalase (+)
DX: Biopsy, Serum IgM, skin test [Lepromin]
TX: Must use multi-drug regimen [Dapsone, Rifampin; Minocycline, Ofloxacin]
May have to give
drugs for several years (5-10) and even for life
Corynebacterium diptheriae
Member of Mycobacteriaceae family
G(+) bacillus, can be pleomorphic (club like) {Coryne = club; diphtheria = hide}
Weak Acid fast (less Mycolic acid in cell wall, shorter chain than rest of family)
Older cells store inorganic phosphate that will appear as metachromic granules
Some thin spots in cell wall lead to gram stain variability
Aerobic
Nonmotile
Normal flora: nasopharynx, skin (Diptheroids) [Humans are the reservoir]
Three strains / biotypes: gravis, intermedius, mitis. Most severe disease with gravis.
Transmission: direct via respiratory droplets
Incubation: 2-3 days
Disease:
Diptheria: pseudomembrane that forms from destroyed tissue and coats
the surface of the pharynx causing obstruction that leads to death.
First appears whiteà blueàgray/greenà black (necrotic), bleeding
Complications due to toxin spread
* Edema: submandibular regions {bull neck}
* Mycoarditis à abnormal rhythmsà heart failure
* Neuritis à motor nerves of head and neckà respiratory
* Thrombocytopeniaà low plateletsàbleeding
* Cutaneous: rash and ulcers, less severe disease, nontoxogenic
* Other mucous membranes
Nasal= mucopurlent discharge
Laryngeal: can be only site, or extension of pharyngeal
Conjunctiva
Vulvo-vaginal
External auditory canal: Otitis media
Virulence
~ Diptheria toxin: A-B exotoxin that inactivates a translation factor and stops protein synthesis.
Bacteriophage can carry gene that allows for toxic strains
~ Neuraminidase: splits NAN to create pyruvate for
cellular energy
~ dipthin: protease that inactivates IgA
Dx: Culture: use of Tellurite media, Corynebacteria produce jet black colonies
Schick test (Diptheria toxin into skin, used to screen)
ID toxin
TX: Antibiotics [erythromycin, IM procaine penicillin]
Antitoxins: will neutralize circulating toxin to help prevent dz progression
Prevention: Vaccination schedule [DTP= Diphtheria, Tetanus, Pertussis]
ID chronic carriers
Limit exposure to sources (Asia, Soviet Union area)