Microbial diseases, part 1:

skin and respiratory diseases

BIOS 303: Lecture 18
Lecture 18: skin and respiratory diseases
§ The normal microbiota of the skin

§ Skin diseases
§ Bacterial: Propionibacterium, Staphylococcus,
Streptococcus
§ Viral: chickenpox/shingles, measles, herpes, and warts
§ Fungal: Candida albicans

§ Respiratory system, part 1: microbiota and defenses

§ Upper RT diseases: S. pyogenes and the common cold
§ Lower RT diseases (more in Lect. 19): influenza
 Normal microbiota of the skin
§ Resistant to drying, relatively
high salt concentrations

§ Often live on sebum -> fatty

acids (inhibit other microbes)

§ Live in small clumps

§ Washing reduces numbers

but does not eliminate
§ Remain in hair follicles/
Tortora
glands; quickly reestablish

See text tables: normal microbiota by body site

 Common groups of skin microbiota
§ > 200 genera, but Staphylococcus (S. epidermidis, S.
aureus) and two actinobacteria (Corynebacterium and
Propionibacterium) predominate
§ Also Micrococcus, β-proteobacteria, etc.

§ Most considered commensal, but some mutualistic

(colonizing and acidic pH)
§ Some opportunistic pathogens (S. aureus, P. acnes)

§ Fungi: Pityrosporum on face/chest/etc., Malassezia furfur

(grows on skin secretions; may cause dandruff!)
 Bacterial skin diseases: acne
§ 17 million people in U.S.; 85%
of teenagers (hormones
contribute)
Severe acne
§ Moderate acne is due to
inflammation, not infection

§ Skin cells shed in hair follicle + sebum -> clog the follicle

§ Propionibacterium acnes metabolizes sebum in clogged

follicle -> forms fatty acids
§ -> Induce inflammatory response; neutrophils secrete
enzymes that damage follicle wall
§ -> Leads to papules and pustules
Tortora et al.
 Bacterial skin diseases: acne
§ Diet has no known effect on sebum production

§ Since due to clogs/sebum,

therapy = prevent formation

§ Oral/topical antibiotics (e.g.,

tetracyclines)

§ OTC benzoyl peroxide targets, dries out skin (loosens

clogged follicles)
 Staphylococcal skin infections
§ S. epidermidis is less often pathogenic
§ Coagulase-negative

§ S. aureus: more common

opportunistic pathogen

§ Coagulase +: enzyme; clots ( )

blood fibrin on its surface =
evades phagocytosis Staphylococcus aureus
§ + correlated with toxins, other virulence factors
 Other virulence factors of S. aureus
§ Toxins facilitate spread, damage tissue, kill immune cells:

§ Alpha toxin, delta toxin: damage cell membranes

§ Leukocidin destroys leukocytes; hemolysins lyse red

blood cells et al.

§ Exfoliative toxin: causes outer layer of skin to peel

§ Toxic shock syndrome toxin: rash, other TSS

symptoms (superantigen)

§ And many others!

 S. aureus skin diseases
§ Folliculitis: infection of the hair follicle; varying severity
§ Pimple (skin) or sty (eyelash)
§ Furuncles (boils) and carbuncles
(hard; deep under skin)
Folliculitis (Atlas of Paediatric HIV Infection)
§ Impetigo (non-bullous): pustules-
rupture, form crusts (heal w/o
treatment or scarring; topical antibiotics)
§ Kids 2-5 common; highly contagious (autoinoculation)
Boil
Sty Impetigo
 S. aureus skin diseases
§ Scalded skin syndrome: bullous impetigo; localized
infection, but affects entire skin
§ Exfoliative toxin: separates dermis and epidermis
§ Toxin A stays localized; B circulates to distant sites

§ Skin becomes blistered (loss of

epidermis), then wet and looks
“scalded”

§ Starts near mouth (red patch);

spreads through body w/in 24 h
Tortora et al.
§ Most common in infants; nursery outbreaks
 S. aureus skin diseases
§ Toxic shock syndrome (TSS): fever, vomiting, and
sunburn-like rash, followed by shock and sometimes
organ (kidney) failure

§ Up to 50% mortality

§ Toxic shock syndrome toxin 1 (TSST-1): superantigen

§ 1980: originally associated with staphylococcal growth

on new, highly absorbent tampon

§ Now rare
 MRSA: Methicillin-resistant S. aureus
1. Hospital associated MRSA: nosocomial infections

2. Community associated MRSA (CA-MRSA)

§ Non-nosocomial; usually skin, can go systemic
§ Can acquire through contact sports, sharing towels,
clothes, athletic equipment
§ Crowded living conditions

§ Vancomycin-resistant strains exist

§ “Later line” (e.g., sulfa) drugs still can be effective
§ Proper cleaning/draining/disinfecting of infection site
can aid in recovery
§ Prevent spread with good hygiene: wash hands
thoroughly; keep wounds clean/dressed until healed
 Streptococcal virulence factors
§ Primarily group A streptococci (GAS) = Streptococcus
pyogenes

§ M protein: helps adhere; evades

complement, resists phagocytosis

§ β-hemolysin (lyse RBCs et al.)

§ Erythrogenic toxin (scarlet fever)

§ Leukocidin destroys leukocytes, streptolysin lyses

erythrocytes

§ Some enzymes facilitate rapid spread in tissue

Tortora
 Streptococcal skin diseases
§ Skin infection often localized

§ Impetigo = pyoderma; direct contact with person/fomites

§ Erysipelas: infects dermis; red patches, raised margins

§ Progresses to local tissue destruction, bloodstream
§ Treat with β-lactam antibiotics (cephalosporin)

Tortora
 Streptococcal skin diseases
§ Necrotizing fasciitis: tissue death of the fascia
(membranous layer of connective tissue)
§ Enter via skin break (wound, etc.)
§ Some others (S. aureus, E. coli, etc.) rarely cause

§ Do NOT actually eat flesh, but destroy tissue

§ A media misnomer
§ Needs several special
tissue-destroying toxins =
few strains cause it!

§ Exotoxin A: major virulence factor

§ Superantigen; IS contributes to damage
Tortora
 Necrotizing fasciitis disease
§ Early symptoms may be vague (sore, pulled muscle)
§ May feel disproportionate pain for a small wound
§ Early may also see purple/black spots

§ Infection may proceed rapidly to underlying muscle

§ Untreated, can lead to toxic shock syndrome, death

§ As fast as 1-4 h, so key to survival is early detection!

§ Docs should treat as such to be on the safe side

Tortora
 The good news
§ Extremely rare, especially among the healthy and those
with good hygiene (= wash cuts!)

§ Most common in high-risk groups: weakened immune

systems, nosocomial, diabetes or kidney disease

§ Main cause responds well to antibiotics; broad-spectrum

drugs usually

§ Surgery to remove dead tissue/prevent spread

§ Are other strep groups (e.g., Group B-infant septicemia)

CDC
Staphylococcus aureus causes all of the following
diseases EXCEPT:
A) Folliculitis
B) Erysipelas strep pyogenes
C) Impetigo
D) Scalded skin syndrome
E) Toxic shock syndrome

All of the following are virulence factors that contribute

to Streptococcus pyogenes pathogenesis EXCEPT:
A) Leukocidin and streptolysin
B) Exotoxin A
C) M protein
D) Exfoliative toxin Staph aureus
E) Erythrogenic (reddening) toxin
 Varicella virus: chickenpox
§ Herpesvirus varicella-zoster

§ Highly contagious; usually occurs in

children

§ Enters via respiratory tract/eyes and

replicates there

§ Skin lesions 14-16 days after

infection

§ Can move to ganglia near the spine

where it remains latent indefinitely…

BSM
 Varicella virus: shingles
§ Latent herpesvirus varicella-zoster

§ Adults/elderly
§ Reactivates by stress,
weakening of immune system

§ Discolored skin lesions like

chickenpox, but painful
§ Usually on trunk, confined to one
region

§ Treat w/ antivirals like valacyclovir

§ Vaccine 97% effective
Tortora
 Herpes simplex virus: cold sores
§ Herpes simplex virus type 1 =
HSV-1 (HSV-2 in Lect. 20)

§ Cold sores around mouth

§ May also infect mucous membranes

§ ~90% of U.S population infected

§ Latent in nerve ganglia

§ Recurrence can be triggered by
UV, emotion (“the Hulk virus”),
hormonal changes, etc.
Tortora
 Rubeola virus: measles
§ Enters via nose, mouth and eyes

§ 9-12 days after infection: macular rash

first appears on face, then spreads

§ Koplik’s spots (white spots with central

bluish specks) in mouth; diagnostic

§ Severe disease with fever, cough,

conjunctivitis; encephalitis may occur

§ Vaccine (part of MMR) has greatly

reduced incidence
Atlas of Paediatric HIV Infection (R. Oladokun)
Rubeola virus: MMR vaccine efficacy
 Human papillomavirus (HPV): warts
§ Bony skin projections formed by proliferation of cells

§ Over 50 types of Papillomavirus

cause warts
§ Incl. genital warts (Lect. 20)
§ A few rare types associated w/
skin, cervical cancer (Lect. 20)

§ Treated with cold liquid N2

(cryotherapy), zapping (electricity), or
burning (acids)
 Fungal infection: Candidiasis
§ Candida albicans
§ Opportunistic pathogen; can
colonize skin, mucous
membranes

§ Vaginitis: vaginal candidiasis

§ Skin: small, white pimples,

rash (immunosuppressed);
topical antifungals
= serious problem in AIDS patients

§ Thrush: oral candidiasis

(infants)
Tortora
Respiratory system microbiota and immunity
§ Upper: Staphylococcus, Streptococcus, Neisseria,
Corynebacterium, Haemophilus, other gram-negatives
§ Microbial antagonism: keep opportunistic at bay
§ Lower almost sterile (immune system)

§ First line: nose hairs trap dust/larger Tortora

particles; mucous traps many microbes
§ Ciliary escalator: cilia on LRT
mucous membrane cells expel
microbes upward

§ Second line: alveolar macrophages

§ Third line: secretory IgA antibodies

 Upper resp. tract: streptococcal
pharyngitis (strep throat)
§ Local, severe inflammation and fever
§ Tonsillitis may accompany
(white, pus-filled lesions)

§ Transmit via respiratory secretions

§ Group A strep (GAS) = S. pyogenes

§ Most still penicillin-sensitive

§ Most sore throats not due to strep!

§ GAS presence ≠ cause

§ Scarlet fever if has erythrogenic

(reddening) toxin; rheumatic fever Tortora
 The common cold
§ Caused by _____________
influenza virus

§ Most rhinoviruses (~30-50%)

§ Coronaviruses (2nd most: ~10-15%),

adenoviruses, etc.
Rhinovirus:
§ Coughing, sneezing, runny nose, etc.

§ 1 rhinovirus is sufficient to cause a cold

Coronavirus:
§ Grow best in URT-bit below normal
body temp
Common cold treatment and transmission
§ No real treatment: many viruses = no vaccine
§ Symptoms usually relatively mild, so therapy = relief

§ More cases in colder weather; unclear why (may be close

indoor contact, physiological changes, or both)

§ Transmission not totally clear

§ Seems via airborne water vapor droplets

§ Low winter humidity, droplets smaller, in air longer
§ May facilitate person-to-person spread

§ Seems direct spread also possible and via fomites for

several hours post-contamination
 Lower respiratory tract: influenza (flu)
§ Chills, fever, muscular aches, headaches, etc.

§ Usually recover w/in a few days; cold-like symptoms as

the fever subsides

§ Virus in the lungs can cause pneumonia

§ Even in non-epidemic years, ~30-50,000 Americans die

annually of the flu

§ Stomach “flu”: intestinal pathogen, not influenza virus!

 Influenzavirus
§ Enveloped RNA virus
§ Genome: 8 separate RNA
segments

§ Envelope spikes:

§ Hemagglutinin (HA or H): help

recognize, attach to body cells
(major Ab target)

§ Neuraminidase (NA or N): seem to

help virus separate from cell during
exit
Tortora
 Classifying Influenzavirus
§ Two subgroups: Influenza A and B
§ A is most pathogenic to humans, birds, other animals

§ Strains IDed based on variation in the HA and NA

antigens
§ E.g., H1N1, H5N1, etc.

§ Antigenic variation (Lect. 16): changes in HA and NA

antigens help evade host immunity
§ Sometimes big changes = a lot of the population
does not have immunity

§ 1918-19 pandemic: H1N1; ~50 million died (likely more)

Two types of Ag variation in Influenzavirus
1. Antigenic drift: accumulated mutations lead to minor
HA and NA Ag changes
§ Allow virus to elude previous host immunity
§ Local outbreak; every ~2-3 years
§ E.g., H2N2 virus still H2N2, but can infect again

2. Antigenic shift: major Ag changes

§ Allow to evade immunity in most of the human pop.
§ = epidemics or pandemics (> 10 years)
§ Reassortment (genetic recombination) of the 8 RNA
genome segments
§ Combines segments from different strains (e.g.,
H1N1 + H5N5 -> H5N1)
 Antigenic shift (reassortment)
§ Different host strains mixing genome segments in a
common host:

§ E.g., humans not affected by most avian flu strains, but

both types infect swine and wild birds -> reassortment
 Practice: Ag drift vs. shift

Feature Ag drift Ag shift

Ag change Minor major

Genetic cause accumulated mutations reassortment

Strain e.g. seasonal flu pandemic

Normal host(s) Human everyting

Frequency occurs continuously less frequent.

Epidemiology localized pandemic, outbreaks

 Influenza epidemics and vaccines
§ Epidemics occur almost every year-not always worldwide

§ Why do we need a new annual flu vaccine? ___________

§ Collection of HA and NA Ags predicted to be common
in the coming flu season
§ Based on strains seen in population in ~February
§ Usually target three of most important strains in
circulation

§ Two types of vaccine: injected inactivated and live

attenuated nasal spray—neither give you the flu!
§ Labor-intensive production in egg embryos = why
need 6-9 months lead time
 Influenza vaccines and treatment
§ Both are perfectly safe, as long as you’re healthy
§ Flu shots = dead; nasal spray = only grow at cool
temps
§ Some questions about spray efficacy; not use in
recent years

§ Mild side effects for 1-2 days: soreness, redness, and

swelling at the injection site
§ Fainting (mainly teens), headaches, low fever, nausea

§ Antivirals: Zanamivir (inhaled) and oseltamivir (Tamiflu;

orally administered) inhibit neuraminidase
§ Shortens symptom duration and lowers mortality

CDC