exam 2 Flashcards
What are the general challenges and physiological conditions microbes face whenever they colonize a host site (first part of lecture on Skin Microbiota)? How do microbes live (form colonies-or not) in their hosts?
-They must be able to adhere to some substratum and not get flushed out- adhere to human cell directly, extracellular matrix, molecule secreted by another microbe
- they must satisfy nutritional needs and growth requirements-not always trivial
-must withstand host defense- a moving target
-must withstand changes in environment caused by other microbes- may actually be an asset
colonies/communities:
-microcolonies- usually enclosed in polymer
-biofilm- teeth, crypts `of tongue
-intracellular colonization- epithelial cell of mucosa
-planktonic- free, least common
What are the predominant biological determinants that affect the ability of the microbiota and pathogens to colonize a site?
Physiochemical determinants:
-temperature- most organisms must be able to grow at 37 degrees C, may affect eye flora and some diseases like leprosy (33 degree optimum)
-pH (1.5-8)
-atmospheric composition- aerobic, microaerobic, anaerobic
-water activity- relates to NaCl levels too
Water availability: areas like some parts of the skin are very dry. If <60, microbes can’t grow
High salt can reduce water activity
Many other parts of body are bathed in fluids
Secretion of lipid-rich substance
-light-UV exposure
Autogenic succession
microbes affect the environment, may be competitive or synergistic- so bacteria that initially colonize an area make it habitable for others who otherwise would not be able to
skin: Face, forehead, behind ear, back, sides or nostril
Structure/Parts
Face, forehead, behind ear, back, sides or nostril
Environmental factors
Sebaceous
-high density of sebaceous glands, hair and eccrine glands
Environmentally exposed
Antimicrobial Defenses
Physical and chemical barriers:
-air flow across surface prevents microbes from settling on skin
-intact stratum-prevents access
-desquamation-shedding-removes adherent microbes
-pH, dry, antimicrobials, lysozyme
Innate immunity:
Neutrophils, nitric oxide, toll-like receptors
Acquired immunity: SALT (skin associated lymphoid tissue), dendritic cells, cytokines, lymphocytes, mostly IgA secreting
Main types of bacteria in each area
Propionibacterium-lipophilic
Dry (palm)
Structure/Parts: Dry (palm)
Environmental factors: Thick stratum corneum
Hairless
High density of eccrine gland
Antimicrobial Defenses: - IL1 complement, TH17
Main types of bacteria in each area: -Propionibacterium
-Firmicutes: streptococcus,
veillonella
-Proteobacteria
-A few gram neg
Moist (axilla)
Environmental factors:Apocrine glands present
High density of hair
Occluded, humid environment
Main types of bacteria in each area: -staphylococci occupy aerobic niche, use urea as nitrogen source
-corynebacteria- play big role
Antimicrobial Defenses: antimicrobial peptides- IL1 complement, TH17
- What are some features that contribute to the large variation in Skin Microbiome?
Host physiology- sex, age, site
Environment- climate, geography, location
Immune system- previous exposures, Inflammation
Host genome- susceptibility genes such as filaggrin
Lifestyle- occupation, hygiene
Pathobiology- underlying conditions such as diabetes
Defenses of the Skin
Physical and Chemical Barriers • Flow of air across surface, prevents microbes from settling on skin • Intact stratum-prevents access • Desquamation-sheddingremoves adherent microbes • pH, dry, antimicrobials, lysozyme Innate Immunity • neutrophils, Nitric Oxide, Toll-like receptors Acquired Immunity- SALT (Skin- Associated Lymphoid Tissue), dendritic cells, cytokines, lymphocytes, mostly IgA secreting
What are the dominant bacterial phyla found and 3 dominant bacterial genera? Are there non-bacterial genera present-what is the most common one? Make sure you know these four genera.
4 dominant phyla: – Actinobacteria (52%) – Firmicutes (24%) – Bacteroidetes (16.5%) – Proteobacteria (6%) Dominant bacteria: -Corynebacterium: gram positive bacilli 8/59 species typically found, non-encapsulated, non-motile, unusual cell wall containing mycolic acid, facultative or aerobic, some don’t produce their own lipids.
- Propionibacterium: gram positive, accounts for ½ of skin microbiota, cause acne, hydrolyze troglycerides and release fatty acids, obligate anaerobe or microaerophilic
- Staphylococcus: 17/35 species found on skin, gram positive, halotolerant, important opportunistic pathogens, ferment sugars to lactic acid
Non-prokaryotic inhabitants:
Eukaryotes:
-Malassezia: dominant of skin fungal populations, dominant in most places expect foot
-Aspergillus
Visuses/Phage”
-Many phage, animal viruses: human papillomas, Polymavirus, retroviruses
- What factors can lead to skin dysbiosis?
Dysbiosis (is a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota)
Mechanisms by which skin microbacteria may initiate or amplify skin disorders:
-genetic predisposition-barrier defect
Increased microbial density
Contextual pathogens-pathobionts
Co-infection
Increase in defined bacteria- inflammatory
- What is the correlation between acne and atopic dermatitis to the skin microbiome?
Atopic dermatitis- makes skin red and itchy- long term- skin can flare up, patients are colonized with S. aureus, causes eczema
Acne: propionobacter acnes, causes activation of complement
- What are features of S. aureus that contribute to its environmental resilience?
Salt tolerant, dessication tolerant
Most have protein A: binds Fc region (activate immune system) of IgG
Have tremendous genetic diversity- transduction, conjugation and transformation
- For Staphylococcus aureus of the skin pathogens know:
a. Basic biology and contribution of this to disease
b. Reservoir and mechanism of transmission
c. Major sites of colonization
d. Major sites of disease – are they the same or different than colonization sites
e. Main diseases
f. Major virulence factors
g. Main disease symptoms (if applicable)
Gram positive firmicute coccus
Facultative-areobic respiration and fermentation
Salt and dessication tolerant
Produce coagulase A (primary indicator used to identify it)
Main reservoir: humans, present transiently on companion animals
Transmission is direct or indirect:
-direct-skin to skin, resp secretions
Transmitted via fomites (towels, sponges)- viable for weeks outside host
Introduced into food
Nose, hands, chest skin, ankles, arms
Invasive infections in almost every organ in the body:
-bacteremia-bloodstream infection
-septic shick
-toxic shock syndrome
-endocarditis (heart)
-meningitis (brain)
Skin and soft tissue infections (SSTI): pimples, boils etc
Ulcers- open sores or craters, folliculitis- hair follicle
-Antibiotic resistance to methicillin and vacomycin is a huge problem
-Has protein A which binds the Fc region of IgG
-MecA which is methicillin, vancomycin etc resistant
-Has adhesions, enzymes that are degradative: facilitate tissue degradation- ex: nuclease- degrades NETs, protease- degrades structural proteins
-Toxins: alpha- forms pores, gamma- also pore forming, exfoliative toxins- serine proteases that destroy adhesion between cells in the epidermis, toxic shock syndrome toxin-1 is a cytotoxin and superantigen
Immune evasion (innate, complement, adaptive, intracellular)
Antibiotic resistance
Maintain skin health
Increased monitoring of populations
Public health practices to decease transmission
Antibiotic resistance is a problem, no vaccines
Mycobacterial leprae
know:
a. Basic biology and contribution of this to disease
b. Reservoir and mechanism of transmission
c. Major sites of colonization
d. Major sites of disease – are they the same or different than colonization sites
e. Main diseases
f. Major virulence factors
g. Main disease symptoms (if applicable)
Gram pos Slow growing Erobic intracellular Preference for cooler regions Bacterial tropism for macrophages and schwann cells
Leprosy
Chronic granulomatous infection skin and peripheral nerves
Nerve damage- mediated by cellular immune response and inflammation
Chronic inflammation
Get taken up by Schwann cells, grows slowly
Host genetic factors effect development of disease and patterns
Macrophages, not the causative M. leprae initiate host nerve demyelination and axonal damage
Large hypo pigment on skin
Mycobacterium ulcerans know:
a. Basic biology and contribution of this to disease
b. Reservoir and mechanism of transmission
c. Major sites of colonization
d. Major sites of disease – are they the same or different than colonization sites
e. Main diseases
f. Major virulence factors
g. Main disease symptoms (if applicable)
Emergind disease
Associated with wetlands in tropical wetlands
Neglected but treatable disease
Very similar to M. marinum which is a fish pathogen
Transmitted by insect bites
Reservoirs are insects, humans
Infection leads to progressive destruction of skin
Painless, mobile swelling of skin or diffuse swelling of limbs
No pain or fever, often not treated, may lead to massive ulcers sometimes bone deformities
Mycolactone: is a toxin
Is cytotoxic by unknown mechanism at high concentrations- causes localized necrosis
Is immunosuppressive at lower concentrations
-inhibits production of TNF by macrophages,
-suppresses dendritic cell activity
-inhibits macrophages, B cells, T cells
-inhibits IL production
Painless, mobile swelling of skin or diffuse swelling of limbs
leishmaniasis know:
a. Basic biology and contribution of this to disease
b. Reservoir and mechanism of transmission
c. Major sites of colonization
d. Major sites of disease – are they the same or different than colonization sites
e. Main diseases
f. Major virulence factors
g. Main disease symptoms (if applicable)
Neglected tropical disease
Type of disease depends on host and pathogen:
-cutaneous: localized, diffuse
Post
Mucocutaneous: visceral
Transmitted through bite of sand fly
Obligate intracellular pathogen- mostly macrophages but other cells- neutrophils
Prevents phagolysosome fusion
Also affects antigen presentation and hamper ability of CD8+ T cells to kill infected cells
Skin sores that heal very slowly
Stuffy nose, runny nose, nosebleeds, swallowing difficulty, ulcers and wearing away in the mouth, nose and inner nose
- What are features of S. aureus that contribute to its environmental resilience?
Salt tolerant, dessication tolerant
Most have protein A: binds Fc region (activate immune system) of IgG
Have tremendous genetic diversity- transduction, conjugation and transformation
Be able to give one example of the degradative enzymes, adhesins, toxins and anti‐immune functions that are used by S. aureus. What are three possible roles of adhesins in disease?
Also use immune evasion and antibiotic resistance- not all strains produce all factors
Adhesins: extracellular matrix binding protein, elastin binding proteins, Protein A, collagen binding protein, clumping factor A etc
Toxins: cytotoxins- taget leukocytes,
What is a MSCRAMM?
Microbial Surface components recognizing adhesive matrix molecule
adhesin proteins mediate the initial attachment of bacteria to host tissue, providing a critical step to establish infection
- What is the mechanism of resistance seen in MRSA strains? Vancomycin? What is different about Community Acquired MRSA (compared to Hospital Acquired)?
MRSA: methicillin resistant
Have the MecA gene which allows bacteria to be resistant to antibiotics like methicillin, penicillin and other penicillin-like antibiotics
Mechanism: PBP2 (penicilin binding protein) is a PG peptidase (catalyzes amino acid transfer- allowing cell wall synthesis) and is a target for Beta-lactams (antibiotics). MacA gene (encodes PBP2) which beta-lactam drugs can’t bind to
Vancomycin binds D-ala-D in crosslinks (resistance bacteria have D-ala, D-lac), but resistant strains don’t let it bind.
There are multiple independent origins:
CA-MRSA: community associated-
- have chromosomal genetic elements: mecA- so have B-lactam resistance
- Secreted toxins and factors
- Global gene regulators- ex: ag, sarA which upregulate many virulence factors
- efflux pumps: prodive fitnass advantage
- vancomycin resistant
HA-MRSA: hospital associated
- How are virulence genes regulated in staphylococci, how does this related to the relationship between colonization and disease?
The accessory gene regulator (agrA) locus of Staphylococcus aureus encodes a two-component signal transduction system that leads to down-regulation of surface proteins and up-regulation of secreted proteins during in vitro growth
-it regulates other genes
Adhesins, invasins and evasins lead to colonization, which leads to toxin production, which promotes disease and transmission
- What are some features of M. leprae that makes it difficult to study this pathogen?
Occurs in resource poor countries, tropics and warm temperate regions (so resource rich countries like the U.S won’t study it)
Cannot be grown in vitro
Prefers cooler regions
has a small genome, and many pseudohenes
- What is one feature of M. leprae biology that limits its ability to cause systemic disease?
It prefers cooler regions- so usually occupies limbs which are cooler in temperature
- What are the two poles of leprosy disease manifestation and how do they differ? How does this relate to the hosts immune response-specifically?
The two poles are tuberculoid pole or lepromatous pole
Exposure to leprae can either cause no disease or end in indeterminate leprosy(ill-defined, hypopigmented skin lesions)-> this can lead to either spontaneous healing or the patient enter a clinical spectrum where it can lead to TB (which involves more cell-mediated immunity) or lepromatous (which involves less cell-mediated immunity)
In tuberculoid- poor Th1 responses and strong Th2 responses, so make strong antibody response and impaired macrophage activation= is an aggressive disease
In lepromatous- strong Th1 response and low levels of Th2 antibodies= limited progression disease
- What cell types are targeted by M. leprae and how does this contribute to pathogenesis and disease symptoms?
Machrophages and schwann cells- In macrophages- nerve damage mediated by cellular immune response and inflammation, causes chronic inflammation, cell wall contrains important targets for host immune response-infect progenitor cells->grows in them-> recruits and transfers bacteria to macrophages-> granuloma formation-> release of infected macrophages
Macrophages and not the causative bacterium M. leprae, initiate host nerve demyelination and axonal damage
In schwann cells (cells that cover the nerve fibers in the peripheral nervous system): grow slowly, host genetic factors effect development of disease and
Pattern->causes infected smooth muscle and infected skeletal muscle
- What is the relationship between M. marinum and M. ulcerans
M. ulcerans has an almost identical genome to M. marinum which is a fish pathogen- only difference s that M. ulcerans replicates more slowly, has no pigments, gained important macrolide cytotoxin mycolactone- toxin
- What is the main virulence factor of M. ulcerans, what disease does it cause, and what are the biological activities of this factor?
May be transmitted by insect bite
Infection leads to progressive destruction of skin
Painless, mobile swelling of skin or diffuse swelling of limbs
No pain or fever, often not treated
May lead to massive ulcers sometimes bone deformities
Has mycolactone which is cytotoxic by an unknown mechanism, it caises localized necrosis
It is immunosuppressive at lower concentrations- inhibits production of TNF by macrophages, suppresses dendritic cell activity, inhibits macrophages, B cells, T cells, inhibits IL production
- What is the causative agent of Leshmanisis and what are the general features of this microbe? What is the role of the insect?
Causative agent: Leishmania spp.
It is protozoan
Transmitted through bit of sand fly
Obligate intracellular pathogen- mostly macrophage but also others
Prevents phagolysosome fusion through LPG-modified lipid microdomains which block the fusion
Causes a variety of diseases- cutaneous is our focus
Type of disease depends on host and pathogen:
-cutaneous: localized, diffuse
-post: dermal
-mucocutaneous: visceral
Skin sores that heal very slowly, stuffy nose, runny nose, and nosebleeds
Difficulty swallowing,
Ulcers and wearing away (erosion) in the mouth and nose and inner nose
Breathing difficulty
- In which type of host cells can it reside and what are two ways it can accomplish its survival in these cells?
Leshmanisis
It is an obligate intracellular pathogen- mostly lives in macrophages but also neutrophils
Has a lot of mechanisms to live intracellularly- avoids phagolysosome acidification by preventing phagolysosome fusion
Also affects antigen presentation and hampers ability of CD8+ T cells to kill infected cells
Cheeks, lips, palate
Antimicrobial Defenses Main types of bacteria in each area
Desquamation (skin shedding)
Saliva Low diversity
Streptococcus predominates
Some periodontal pathogens persist by invading buocal cells
Teeth
Environmental factors Antimicrobial Defenses Main types of bacteria in each area
Environmental factors Antimicrobial Defenses Main types of bacteria in each area
Non-shedding
Stagnant sites: food impaction possible Saliva influences this Diverse microflora, site variation
Many obligate anaerobes
Stepto
Actinomyces
Veillonella, fusobacteria, prevotella, Treponema, unculturable organisms
Tongue
Highly papillated surface Has some anaerobic sites Desquamation Diverse microflora Facultative and obligate anaerobes Stepto, actinomyces, Rothia, Neisseria, some gram neg anaerobes
- What are the 4 main bacterial phyla found in the oral cavity? How, in general does the oral cavity differ than other sites?
Proteobacteria
Actinobacteria
Bacteriodetes
firmicutes
- What is a biofilm? Know the relationship between the microbes in saliva, tongues and in plaque
Each tooth is an island-hard surface, near constant presence of liquid
Sites on same tooth are variable
Biolfilm is a cluster of bacteria
There are some microbes that are present in saliva, tongue and plaque such as streptococcus
- Know the terms adhesion, coadhesion, and coaggregation and how they play into the formation of a biofilm on teeth. What has current research on oral biofilms revealed about the spatial organization of the biofilm?
Adhesion-microbes can recognize specific sites to adhere to- ex: streptococci can recognize receptors in salivary pellicle
Coadhesion- planktonic microbes can adhere to genetically distinct microbes
Coaggregation- bonding of 2 distinct microbes suspended in fluid phase
Plaque formation is dependent on signals- nothing is random
Autoinducer 2 is a universal intergeneric signal
Time and spatial relationships are critical for plaque formation
Signaling across even across domain
And nutrients and DNA are exchanged
spatial organization: a cauliflower structure, using tooth side and base between teeth, or in plaque or corncob
