Skin & STD Infections

Staphylococcus aureus

• Staphylococcal immune avoidance

  • Impairment of phagocyte recruitment

  • Interference with complement activation

  • Resistance to oxidative burst killing

  • Resistances to antimicrobial peptides

  • Nonopsonic binding or degradation of immunoglobins

  • Cloaking of opsonins

  • Neutrophil lysis

Toxins

• Membrane disrupting toxins

  • Alpha — pore forming

  • Beta — sphingomyelinase

  • Delta — surfactant

  • Gamma — leucocidin

• Exfoliatin

  • Destroys cellular junctions in epidermis

• Enterotoxins

  • Heat / digestive enzyme stable proteins with super Ag activity

• TSST-1

  • Toxic shock syndrome toxin; super Ag activity

• Spreading factors

  • Coagulase

  • Catalase

  • Hyaluronidase

  • Fibrinolysin

  • Lipases

  • Nucleases

  • Beta-lactamases

Staphylococcal Diseases — Invasive (Abscesses)

• Impetigo

  • Bacteria can enter through small breaks in skin

  • More common in most areas of body

  • Contagious by contact, but may begin from bacteria already present

    • Infant to early elementary aged children

  • Topical and/or oral antibiotic treatment

• Folliculitis, furuncles & carbuncle

  • Infected hair follicles (itchy, sore, redness)

  • Cluster can join together and go deeper into the tissues

    • Often associated with more pus production and possible scarring

• Systemic infections may result from dissemination

  • Osteomyelitis

  • Pneumonia

  • Endocarditis

Staphylococcal Diseases — Toxigenic

• Scalded skin syndrome (exfoliatins)

  • Epidermolytic toxins bind desmoglein 1 protein of desmosomes

  • Treatment similar to burn patients, watch for dehydration

• Toxic shock syndrome (TSST-1)

  • Not limited to menstruation

    • Can occur with use of barrier contraceptives and complications of child birth

    • Can occur as infections in both men and women

  • Super antigen activity stimulates over production of cytokines leading to extreme fever, rash, nausea, hypotension, dic, and eventually shock

    • Progresses over 1-2 week period

GAS Diseases

• Throat infections (pharyngitis, tonsillitis)

• Skin infections (pyoderma, cellulitis, erysipelas)

Skin Infections

• Impetigo

  • Superficial skin infection of epidermal layer

  • Highly contagious by direct contact

• Erysipelas

  • Dermis layer to cutaneous lymphatics

  • Red, hard, often warm to the touch

    • Well defined border is often characteristic

• Necrotizing fasciitis

  • Associated with M1 & M3 strains carrying SpeA or SpeB

    • 1:3 people will die even with rapid treatment usually due to septic shock and organ failure

• Poststreptococcal acute glomerulonephritis

  • Resulting from a type III hypersensitivity response to large antigen

  • Antibody complexes trapped in glomeruli

    • Follows skin infections but could follow pharyngitis as well

Pseudomonas aeruginosa

• Gram - bacillus

  • Large, moist, graysih green colonies

  • Fruity odor

  • Aerobic

  • Wide temp. range

• Sources of community-acquired infections

  • Recreational hot tubs, swimming pools

  • Infections in healthy individuals are typically minor

• Pseudomonas is among the few pathogens that grow well in burn exudates, which even enhance expression of virulence factors

  • Pseudomonas will delay healing and can often lead to death of patient

Cystic Fibrosis

• Impaired mucocilliary leads to colonization by Pseudomonas

• Many colonized by age 10, nearly all by adult

• Alginate is major contributor to pathogenesis: biofilm formation, inhibition of phagocytosis, inhibition of oxygen radicals, suppression of lymphocytes, suppression of opsonizing antibodies, & suppression of complement

Papillomavirus — Transmission

• Direct contact through breaks in tissue

  • Physical & sexual contact

    • Rapidly growing STD — now most common

    • 43% of college aged women converted from HPV negative to positive within three years

    • 80% of sexually active individuals will become infected (may be asymptomatic)

  • Divided into two groups based on susceptible tissue

    • Cutaneous HPV (common, plantar, genital)

    • Mucosal HPV (laryngeal, cervical)

DNA Virus — Characteristics

• Benefits of being a DNA virus

  • Can use the host cell transcription and replication machinery

• Problems to overcome as a DNA virus

  • DNA synthesis in eukaryotes does not occur continuously but is confined to the S-phase of the cell cycle

  • Additionally, many differentiated cells rarely divide in multicellular organisms. Viruses must overcome this problem by inducing the cell cycle or replicating in rapidly dividing cells

DNA Virus — Infection

• Binding of viral proteins E6 & E7 to cell cycle regulatory proteins causes uncontrolled mitosis

• One possible outcome of DNA virus infections is transformation of the cell

• When HPV remains independent of host chromosome, it is circular and E6/E7 gene expression remains controlled

• Occasionally, HPV will linearize and insert into chromosome

  • This causes over expression of E6/E7 resulting in tissue dysplasia and possible tumor formation (3rd most common cancer cause)

Neisseria gonorrhoeae

• Gonococcal urethritis & cervicitis

  • The strong inflammatory response and destruction of phagocytes contributes to the discharge

• Anal & oral infections

  • Most prevalent in gay men

• Complications

  • Pelvic inflammatory disease (f)

  • Infection of seminal vesicles, prostate (m)

  • Disseminated gonococcal infection - DGI

    • Arthritis, petechial rash, tendonitis

Virulence Factors

• Pili are used for initial attachment

• Opa proteins are needed for tight adhesion followed by invasion into tissue

• PorA permits resistance to killing by phagocytes (blocks phagosome/lysosome fusion)

• LOS — analagous to LPS — promotes strong inflammatory response

• LOS and PorA also bind regulators of complement to block its activity

Syphilis — Treponema pallidum

• Syphilis is most common among population subgroups with limited resources or who live on the margins of society

  • More common among the poor, those who lack access to healthcare, & many sexual partners

• Treponema is very invasive — corkscrew motility and hyaluronidase permits tissue infiltration

  • Stealth pathogen: lack of LPS and surface antigens allows it to go unnoticed by immune system until too late

Stages of Syphilis

• Primary syphilis

  • Shallow painless ulcer often exuding clear/yellow colored fluid

    • High contagious (phallic, vaginal, oral, anal)

• Secondary syphilis

  • Systemic disease with numerous lesions & flu-like symptoms

    • Still contagious, occurs a few months later

    • Becomes latent for 10-40 years

• Tertiary syphilis

  • Organ involvement, gumma development

    • Is not contagious

Other Types of Syphilis

• Neurosyphilis

• Cardiovascular syphilis

  • Aortic aneurysm, enlargement of the left ventricle, calcification in aorta & arch

• Congenital syphilis

  • During primary: 100% incidence

    • Generally still birth, abortion

  • During secondary: 90% incidence

    • Skin lesions & hutchinson’s triad (dental stigmata, interstitial keratitis, 8th cranial nerve deafness)

Chlamydia trachomatis

• Sexually transmitted urethritis & cervicitis

• Trachoma (blindness)

  • Not STD — transmitted by flies & dirt particles

Chlamydia Life Cycle

• Obligate intracellular parasites — lack the ability to make ATP

• Identifying virulence factors for these medically important pathogens has been severely limited by the lack of genetic tools

  • Attachment protein identified

  • Appears to resist intracellular killing by phagocytes

  • Appears to have antigenic variation in outer proteins

  • LPS is important to infection process

  • Type III secretion system resulting in cytoskeleton rearrangement

  • Chlamydial cytotoxin — requirement for infection?