Microbiology (Bio 205)

1
Microbiology (Bio 205) Pathogens lecture
outline Dr. Rhoads Summer 07
2
Respiratory pathogens
S. aureus 1 significant pathogen? why?
http//www.textbookofbacteriology.net/staph.html
opportunist nosocomial versatility O2
requ., AW, pH, metabolic options, etc AB
resistance MDR, pilus mediated
vancomycin (1993) linezolid (2003)
many toxins/conditions Conditions
typical pneumonia with
lingering inflamation 1 most
common food poisoning enterotoxin
1 most common post-operative infection
toxin super Ag Toxic shock syndrome
toxin super Ag Skin
impetigo, Ritters or scalded skin syndrome
coincident wound infections, carbuncles,
boils, styes
UTIs, meningitis, endocarditis, and on and on
3
Some toxins / proteins of S. aureus

invade/spread alpha toxin leucocidin vs
membranes hyaluronidase disseminate
between cells defense protein A bind
Ab in wrong orientation vs recognition
staphylokinase plasmin activator lyses
fibrin clots coagulase fibrin
activator leucocidin vs
macrophages pathology beta
hemolysin exfoliating toxins
enterotoxins TSST-1
superantigen non-specific T-cell and
cytokine proliferation
4

• S. pyogenes same (???) problems as S. aureus
• Group A strep Rebecca Lancefield
• Conditions
  Streptococcal pharyngitis (SCP) rapid strep
  test misdiagnosed for viral
  RSV Adeno Metapneumo
• If systemic various toxins
• Scarlet fever (SF) follows SCP was
  deadly for children immune response to S.
  Pyrogenic Exotoxin (super Ag) vascular
  damage? spiking fever red, sandpaper body rash
  strawberry tongue
• Rheumatic fever kids post SCP/SF joints,
  heart valves, CNS
• Necrotizing fasciitis flesh eating
  bacterium he was the 1st local acute tissue
  damage ? systemic damage shock
  multiple exotoxins super Ag
• Septicemia renal cardiac CNS

5

• A few of the other conditions caused by S.
  pyogenes
• Pneumonia
• Impetigo
• Cellulitis (erysipelas)
• Neonatal sepsis (puerperal fever)
• Glomerulonephritis
• Meningitis
• Osteomyelitis
• Otitis media
• a toxic shock-like condition
• many more

6
S. viridans group (???) of strep species that
commonly exist as a
commensal member of human microbiota are either
alpha or gamma hemolytic lack Lancefield
antigens (i.e. not classified in a group)
generally low virulence, but can cause a
variety of conditions in the elderly or
otherwise immunocompromised dental carries (S.
mutans) endocarditis necrotizing
fasciitis bacterial sepsis urinary tract
infections
7

• Pneumonia pneumo lung
• Consolidation (hardening due to filling
  inter-alveolar voids with fluid cellular debris
  ( maybe other stuff!)) results in
• 1. Restricted thoracic / pulmonary compliance
  2. Exudation?
  Effusion? Protracted inflammatory response
• Typical vs Atypical??? symptoms / pathology
  effectiveness of
  antibacterial treatment
• A) typical similar to pneumococcal pneumonia
  acute exudative
  localized / lobar sharp pain spiking fever
  -cillins / cephalosporins / azithromycinothers
  MDR uber-bacterial
• B) atypical NOT similar to pneumococcal
  pneumonia chronic? not productive
  global pulmonary extra-pulmonary atypical
  effectiveness of antibiotic therapy peculiar
  bacteria

8

• 1) typical pneumococcal-like acute sores
• S. pneumoniae pneumococcus the
  old pneumonia alpha hem. 1
  cause of (80) typical pneumonia?
  bacterial otitis media? meningitis?
  K. pneumoniae Friedlanders
  pilus MDR
• P. aeruginosa epitome of an
  opportunist arsenal of immune defenses
  and toxins nosocomial pneumonia on the
  increase CDC
  1 cause of ICU related pneumonia???
  sepsis in immuno-compromised
  patients (BURN patients)
  pilus MDR Acinetobacter baumanii
  nosocomial! like P.a. pilus MDR!
• S. aureus 3??? protracted inflammatory
  response MDR

9
Atypical pneumonia

• 2) atypical the walking pneumonias macrolide
  s, quinolones, tetracyclines
• a) Mycoplasma pneumoniae 1 atypical??? 1
  walking pneumonia 1 cause in young adults
  no cell wallpennicillin?
• b) Legionella pneumophila Legionaires
  disease 16 mortality condensate from AC,
  frig, water fountain, etc. CYE agar 96
  Christiansburg Lowes 14 cases from jacuzzi
  display
• c) Chlamydia pneumoniae bacteria or
  virus? OIP but antibiotic sensitive
  lytic-like cycle intracellular hard to kill
  misdiagnosis US 65 sero
  300,000cases/yr ???
• Viral 1RSV 2metapneumo orthomyxo
  adeno
• Fungal / protozoan Pneumocystis carinii
  genetically like fungus / otherwise
  protozoan PCP - AIDS

10
Respiratory pathogens continued

• Corynebacterium diptheriae Boston George
  Washington? infection local BUT pathology
  can be systemic due to potent systemic toxin
  only cells lysogenized by virus
  produce the diptheria toxin ie. phage
  encoded pseudo-membrane
  suffocation especially in infants also CV
  damage, paralysis, coma, death
  lt106 annual deaths worldwide only 10
  annual cases in US DPT vaccine
  toxoid (1920s) conjugated (1940s)

11
Mycobacterium

• Mycobacterium
• mycolic (fatty) acids acid fast Gram
  variable 50 envelope hydrophobic
  shell immune defense vs proteins, WBCs
  cord factor in virulent strains
  rope-like cell arrangement is a
  virulence factor 1. toxic to mammalian
  cells 2. anti-phagocytosis via
  macrophages
  Intra-macrophage parasites MP giant cells
  Chronic bi-phasic pathology (CDC 5 stages?)
• Mycobacterium tuberculosis 8-10
  million new cases with 3 million deaths
  annually??? US 20,000 cases with 1000 deaths/
  but decreasing recently antibiotic resistance
  MDR XDR strains REI a few
  macrolides and/or quinolones MDR Predisposing
  factors HIV, alcoholism, other immune issues
  

12

• 1 phase
• MTB cells phagocytized by macrophages (dust
  cells) (1-3) dust cells fuse to
  form MP giant cells tubercles 6-9 months
  giant cells clear MTB cells or not T-cells and
  cytokines join battle contributing to tubercle
  formation low cell (not
  contagious) BUT highly tuberculin sensitive
  fibrous calcified tubercles (Ghon complex) can be
  persistent
• 2-10 years later
• 2 phase contagious phase
• MTB cells abundant BUT lower immune activity
  (4, 5) tubercles grow
  causing chronic necrosis of pulmonary tissue
  caseating granulomas tubercles liquefy
  accelerated MTB growth systemic wasting
  condition not as much a poor urban disease as
  used to be
• Bacillus Calmette Guerin vaccine 50
  effectiveness

13
Respiratory pathogens continued

• Bordetella pertussis whooping cough many
  systemic toxins pertussis toxin paralyzes
  tracheal cilia uncontrollable series of
  coughs anoxic whoop tracheal swelling
  suffocation cases increasing in US since 1980?
  Why? 300,000 deaths/yr. a leading
  cause of vaccine preventable death
• Histoplasma capsulatum fungal (1?)
  Darlings disease inhale bird (pigeon
  1, Starlings, chickens) bat feces
  hyphae can cause severe pulmonary damage
  obvious on X-ray can disseminate to other
  organs high mortality untreated

14
Viral respiratory pathogens review

• Flu Influenza virus
• Common cold rhino, adeno, corona (SARS)

15
CNS meningitis encephalitis
Symptoms headache nausea stiff neck
confusion ??? Neisseria meningitidis
diplococcus meningococcus
1 meningitis 15-24 yrs.??? 15 deaths/yr. in
US ACHA requires vaccine for ???
Dorm? Admissions? Fastidiousso Chocolate
agar X V factors Transmission? Direct
contact via nose throat secretions?
Haemophilus influenza see the name
chocolate agar was 1 meningitis 6
months - 6 yrs. most cases 1 yr. old 20,000
cases with 1000 deaths annually before HIB
vaccine virtually eliminated by HIB vaccine
in late 80s otitis media
Listeria monocytogenes invades monocytes at
least 500 US deaths/yr. food born
from animal feces or blood, hot dogs, dairy,
other ? septic causes meningitis,
encephalitis, uterine infections at risk 3rd
trimester mothers babies, elderly, AIDS
patients mortality from uterine infection mom
baby gt50 teratogen
16
CNS - meningitis continued

• Streptococcus agalactiae Group B strep
  1 of 3 women carry it in their
  genitourinary tract
  transmitted perinatally neonatal meningitis
  mortal intravenous penicillin during labor
  adolescent vaccine???
• Cryptococcus neoformans 1 cause of fungal
  meningitis currently inhaled in bird feces
  migrates to CNS 85 cases in US AIDS
• Toxoplasma gondii 1 protozoan mainly from
  cat feces (litter box) crosses placenta in 1/3
  of infected pregnant women teratogen 50
  of all people are sero() sub-clinical
• Viral meningitis coxsackie echo, rubula, HSVII

17
Viral CNS pathology review NOT on test

• poliovirus
• rubeola
• Varicella-Zoster nerve ganglia damage
• EBV CMV mono
• rhabdovirus negri bodies
• encephalitis viruses

18
Gastrointestinal pathogens diarrhea
dehydration

• Bad water bugs fecal-oral 1 developing
  countries
• Shigella dysentery bacillary dysentery
  blood/mucus flux best enteric pathogen
  1 infectivity very common (1?)
• Salmonella typhi acute gastroenteritis a)
  like dysentery b) can become systemic
  typhoid fever high sustained fever intra-macroph
  age in Peyers patches carried in gall
  bladder perforated ileum liver abscesses
  encephalitis endocarditis Mary Mallon 1900
• Vibrio cholerae curved cells Asiatic cholera
  endemic to India severe diarrhea toxin
  stimulates adenylate cyclase ? cAMP responsible
  for millions of deaths in India
• Hepatitis A virus temporary liver
  dysfunction

19
Bad water bugs continued The Protozoa

• The Protozoan life cycle has various stages
  including a cyst stage very tough similar to a
  bacterial endospore (chlorine resistant).
• Entamoeba histolytica amoebic dysentery
  Montezumas revenge Travellers diarrhea liver
  abscesses acute mortality 20
• Cryptospiridium parvum cysts extremely HClO3
  resistant (1) cyst overload in potable water
  treatment systems spring rains feces
  (mainly cow) other organics in watershed
• Giardia lamblia 1 most common GI parasite in
  N. America 2.5 million US cases annually
  municipal
  recreational H2O, wild mammal reservoirs
  kids!!! outdoorsmen, campers, hikers, etc.
  Beaver fever small aquatic
  mammals as reservoirs

20
B) Food poisoning eating toxins in the food,
and maybe more Staphylococcus aureus 1
most common cause handled foods rapid on-set
short duration relatively mild
Clostridium perfringens obligate anaerobe
MEAT main culprit characteristics similar to S.
aureus food poisoning Bacillus cereus
starchy foods Oriental restaurants buffets
endospores rice / grain dry and
dirty characteristics similar to above, but
can be worse Vibrio paraheamolyticus
common in sea water seafood raw,
undercooked, held too long at room temp more
severe than above 10 day duration Japan

21
Food poisoning continued

• Campylobacter jejuni enterocolitis similar
  to V. paraheamolyticus vs dysentery colon
  small intestine, more severe? more blood?
  poultry, eggs, milk microaerophile
• Salmonella enteritidis 1 week incubation, then
  condition lasts a week GI symptoms (bad ones)
  PLUS headache fever! POULTRY, eggs, pork,
  milk
• E. coli and intestinal disease multiple strains
  severity varies POOP! Worst is E. coli
  0157-H7 tissue liquefying enterotoxin
  hamburger! or water in 3rd world countries
  
• Clostridium botulinum botulism 1 most
  potent toxin on Earth! flaccid paralysis
  prevents acetylcholine from filling gap junction
  only lysogenized cells produce the botulinum
  toxin

22
Miscellaneous GI pathogens

• Helicobacter pylori contributes to ulcers
  80-90! flagellated BUT uses
  corkscrew motion to burrow into stomach
  mucosa unprotected spot
  uses urease (test) ? NH3 from urea a) raises
  local pH b) contributes to irritation
  30-50 infected in US 10 of these get
  ulcers treatment histamine receptor
  antagonists (H2RA) antibiotics H2 RA
  drugs superceded by Proton pump inhibitors
  under-pasteurized dairy products
  linked to gastric carcinoma relation to GERD?
  or - ?
• Clostridium difficile commonly known as cdif
  antibiotic associated
  pseudo-membranous colitis
  toxin damages colon mucosa pseudo-membrane
  opportunist colonizes colon when lacking
  competition nosocomial in 30 of hospitalized
  patients.that..? source natural
  resident of colon

23

• STDs are next. Prepare yourself for some nasty
  pictures!

24
Genitourinary pathogens

• Treponema pallidum syphilis fastidious
  never in vitro Virulence
  ?serverity ?infectivity 6-7000/yr. in U.S.
  STD epithelial breaches congenital
  transplacental / perinatal Spirocheate
  corkscrew motility axial filament
• 1 phase 3 weeks, then external chancre
  genitalia, other no pain? female
  detection unlikely usually 6-8 weeks later
  
• 2 phase ?cell immune response rash
  on palms/soles or??? contagious via intimate
  contact, congenitally, other? Great
  variance in symptoms the great imitator
  .1-30 yrs. later 50 develop..
  
• 3phase 0 or few cells but massive
  delayed-type hypersensitivity
  neuro-syphilis stage teflon pathogen
  horrible pathology granulomas gummas CNS
  CVS blindness insanity death
• Pennicillin works Mozart Henry VIII
  Capone Hitler

25
Genitourinary pathogens continued

• Neisseria gonorrhea vs syphilis ?severity
  ?infectivity 106 in US 2nd only to Chlamydia in
  US??? the gonococcus 4-6 days (up to 30)
  before onset of symptoms
• females 60-90 transmission but detection
  unlikely scarring of oviducts tubal
  pregnancy, sterility
• males 10-35 transmission but urethral
  pathology is painful, purulent and cannot go
  undetected eventual epididymal or urethral
  stricture infertility
• perinatal gonococcal conjunctivitis purulent
  (vs Chlamydia) neonatal treatment with AgNO3
  antibiotics (cillins, cipro,
  
• high incidence 1. no immunity via fimbriae Ag
  changes 2. unaware in females
  ?transmission 3. birth control pill
  78 peak

26
Genitourinary pathogens continued - NGU

• Chlamydia trachomatis remember the OIP
  bacterium?
• ill-defined condition, symptoms vary
  significantly like C. pneumoniae,
  hard to study statistics sketchy
• highly prevalent gt gonorrhea 1 in
  US??? 3 x 106 cases in U.S. many
  asymptomatic ? more contagious in men than in
  women?
• pathology 1. NGU urethritis, cervicitis,
  infertility 2. trachoma ie. inclusion
  conjunctivitis, rough eye transmitted via
  direct contact, fomites arid
  Africa Asia 1x108 cases, 106 blinded 3.
  lymphogranuloma venereum

27

• Trichomonas vaginalis protozoan trich
  trichomoniasis also ?prevalent
  ???106 annual cases in N. America
• females NGU frothy, foul-smelling
  discharge itching pregnancy can result in
  preterm delivery low birth
  weight more severe conditions
• males unaware, asymptomatic urethritis
  vs other STDs
• rarely pathogenic for males
• antibiotic resistance increasing

28
Non-STD urinary tract infections (UTIs)

• Enteric bacteria E. coli and P. mirabilis
  fecal ? urethra motile
  predispositions hygiene diarrhea
  catheters, etc.
  
• Candida albicans yeast thrush urethral
  itching burning predisposition same as above
  disturbing normal flora

29
Parenteral route arthropod vector
Yersinia pestis black plague black death
bubonic plague endemic in European
Asian rodents flea vector highly acute
even kills its own reservoir vector!
Major pandemics (540, 1350, 1700, 1850) killed
108 ? pneumonic bubonic both septic
shock spiking fever bubos hemorrhage
subdermal (GG), pulmonary
Typhus stupor of fever reservoir for most
is wild rodents symptoms red rash
migrates from extremities to trunk fever
arthritis-like neurological abdomen pain
diarrhea Caused by species of Rickettsia
OIPs like Chlamydia Rickettsia rickettsii
Rocky Mtn. spotted fever tick typhus
various tick species 95 of modern day typhus
cases in US all US but Oklahoma N. Carolina
have ?prevalence
30
Arthropod vector continued

• Ehrlichia Richettsias? Typhus? Still up in
  the air but if not, they are very similar via
  symptoms, arthropod vectors, OIPs
• E. chaffeensis causes human monocytic
  ehrlichiosis OIP of
  leucocytes, mainly monocytes (ie. macrophages)
  Deer reservoir Vector lone star
  tick Common in SE US Symptoms
  Typhus-like but rash in only 20 of patients
  Also leucopenia due to WBC destruction
  Often misdiagnosed mortality rate 3
• E. ewingii causes human granulocytic
  ehrlichiosis Similar to E.
  chaffeensis with these exceptions 1. more
  severe with 10 mortality rate 2. parasitized
  cells mainly neutrophils other granulocytes

31
Continued but NOT typhus

• Borellia burgdorferi Lyme, CT spirocheate
  deer tick vector typhus-like symptoms
  bulls-eye rash in 80 patients also CNS
  symptoms bells-palsy, meningitis, stabbing
  pains East coast of US prevalent in
  most of N.E. VA
• female Anopheles mosquito feeding at night
• Plasmodium falciparum protozoan malaria
  black water fever 4-6 hr. cycle of fever,
  rigor/convulsion sweating each 36-48hrs
  anemia / cerebral hemorrhage headache coma
  liver/renal
• 2-5 x 108 infected with 1-3 million deaths
  annually quinine used to work great toxic
  now requires a anti-protozoan cocktail
  quinine derivatives, terramycin, doxycycline

32
Skin/parenteral route NOT arthropod
Clostridium obligately anaerobic endospore
former perfringens gas gangrene via
post-op, umbilicus, trauma lecithinase vs
cell membranes, hemolysin, gas production
tetani tenanus tetanospasmin umbilicus,
trauma cholinesterase inhibitor
spastic paralysis 10yr. toxoid