Skin Infections By: Courtney Chinn

Herpes Simplex Viruses Pseudomonas aeruginosa

Herpes Simplex Viruses 1 and 2 are part of the Herpesviridae family. HSV consists of a relatively large dsDNA
genome encased in a capsid surrounded by an envelope. HSV contains at least 74 genes responsible for
forming the capsid, envelope, and controlling the replication and infectivity of the virus.
P. aeruginosa is a gram-negative, aerobic, rod-shaped bacterium with unipoloar motility; it can also be considered as facultatively anaerobic. This organism can achieve
anaerobic growth with nitrate as a terminal electron acceptor, and, in its absence, it is also able to ferment arginine by substrate-level phosphorylation. This organism is
an opportunistic pathogen as it is part of human’s skin normal flora.
Both HSV-1 and HSV-2 are contagious. HSV-1 causes cold sores, whereas HSV-2 usually produces genital herpes. HSV-1 is normally acquired orally during
childhood, but may also be sexually transmitted. HSV-2 is primarily a sexually transmitted infection. HSV are transmitted from contact with an infectious area of
skin during reactivations of the virus or via direct skin-to-skin contact with another infected human. Transmission can occur during symptomatic or Because P. aeruginosa uses a wide range of organic material for food, the organism is able to infect damaged tissues or people with reduced
asymptomatic infection, as well as during the latent period. HSV may also be transmitted vertically during childbirth, although this is uncommon unless the immunity. When an individual is immune-compromised, a variety of infections can occur. Besides skin infections, pneumonia, septic shock,
mother exposed blisters during delivery or acquires the virus for the first time late in pregnancy. Symptoms resulting from primary infection with HSV are usually urinary tract infections, and gastro intestinal infections are also possible in immune-compromised patients. The capacity of P. aeruginosa to
much more severe than subsequent outbreaks, as the body has not had a chance to produce antibodies. This first outbreak of oral herpes carries a low risk of produce such diverse, often overwhelming infections is due to an arsenal of virulence factors. Burn victims and patients with wound infections are
developing aseptic meningitis. at a risk for developing skin and soft tissue infections due to P. aeruginosa. This organism is also associated with the skin lesion, ecthyma
gangrenosum. Pseudomonas aeruginosa is also frequently associated with osteomyelitis involving puncture wounds of the foot, believed to result
from direct inoculation with P. aeruginosa via the foam padding found in tennis shoes.
Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus with receptors on the surface of
the host cell. Complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. The two membranes
begin to merge, forming a hemifusion state. A stable entry pore is formed through which the viral envelope contents are introduced to the host
cell. Initial interactions occur when glycoprotein C (gC) binds to a cell surface particle, heparan sulfate. Glycoprotein D (gD), binds specifically to at Numerous factors assist P. aeruginosa in its virulence. Adherence to epithelium is mediated by type 4 pili. Flagella may also act as adhesions to epithelial cells. Many extracellular virulence factors
least one of three known entry receptors: herpesvirus entry mediator (HVEM), nectin-1, and 3-O sulfated heparan sulfate. Once bound, gD secreted by P. aeruginosa have been shown to be controlled by a complex regulatory circuit involving cell-to-cell signaling systems that allow the bacteria to produce these factors in a coordinated, cell-
changes its conformation and interacts with viral gH and gL, resulting in the hemifusion state. gB interacts with glycosaminoglycans on the surface density–dependent manner. Cell-to-cell signaling systems might enable P. aeruginosa to overcome host defense mechanisms. Isolated production of extracellular virulence factors by a small number of
of the host cell. Afterward, gB interaction with the gH/gL complex creates an entry pore for the viral capsid. After the capsid enters the bacteria would probably lead to an efficient host response neutralizing these compounds. However, the coordinated expression of virulence genes by an entire bacterial population once a certain
cellularcytoplasm, it is transported to the cell nucleus. Once attached to the nucleus, the capsid ejects its DNA contents via the capsid portal. density has been reached might allow P. aeruginosa to secrete extracellular factors only when they can be produced at high enough levels to overcome host defenses. These factors could alter the
Following infection of a cell, herpes virus proteins, (immediate-early, early, and late), are produced. The early proteins transcribed are used in the precarious balance between host defenses and production of bacterial toxins, leading to invasion of blood vessels, dissemination, systemic inflammatory-response syndrome, and finally death. Even
regulation of genetic replication of the virus. Upon entering the cell, an α-TIF protein joins the viral particle and aids in immediate-early appropriate antibiotic therapies are often unable to stop this course; therefore, the process must be blocked early, before virulence gene expression can be coordinated. Exotoxin A is produced by most
transcription. The virion host shutoff protein (VHS or UL41) shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, P. aeruginosa strains that cause clinical infections. Exotoxin A catalyzes ADP-ribosylation and inactivates the eukaryotic elongation factor 2in the host cell, much as the diphtheria toxin does. The
and regulates gene expression of viral proteins. The late proteins are used to form the capsid and the receptors on the surface of the virus. exotoxin binds to the host membrane and enters via endocytosis. The exotoxin is comprised of two parts: part A and part B that initially bound to each other via disulfide bonds. Part B binds to
Packaging of the genome, core and the capsid occurs in the nucleus of the cell. HSV-1 undergoes a process of primary and secondary heparin, binding epidermal growth factor. Part A then detaches from part B so that Part A can bind to elongation factor 2, causing the ribosome to shut down. Consequently, this shuts off protein
envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear synthesis, so that the cell ultimately dies. Exotoxin A is responsible for local tissue damage, bacterial invasion, and immunosuppression. In addition, P. aeruginosa uses exoenzyme S which ribosylates
membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles. The virus can GTP-binding proteins such as Ras. This exoproduct is responsible for direct tissue destruction in lung infection and may be important for bacterial dissemination. Two hemolysins, phospholipase C and
then exit the cell as an infectious virion via budding. rhamnolipid, produced by P. aeruginosa, may act synergistically to break down lipids and lecithin. Both may contribute to tissue invasion by their cytotoxic effects. Rhamnolipid, a rhamnose-containing
glycolipid biosurfactant, has a detergentlike structure and is believed to solubilize the phospholipids of lung surfactant, making them more accessible to cleavage by phospholipase C. The resulting loss
of lung surfactant may be responsible for the atelectasis associated with chronic and acute P. aeruginosa lung infection. Rhamnolipid also inhibits the mucociliary transport and ciliary function of
HSV may persist as a latent infection in which the virus hangs out in the neural ganglia. During latent infection, HSVs express Latency Associated Transcript (LAT)RNA. LAT human respiratory epithelium. However, the relative role of rhamnolipid in acute or chronic infection is not known.
regulates the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, allowing
subsequent, periodic recurrences or "outbreaks". Whether or not recurrences are symptomatic, viral shedding occurs to produce further infections, usually in a new host.
A protein found in neurons may bind to herpes virus DNA and regulate latency. Herpes virus DNA contains a gene for a protein called ICP4, which is an important
transactivator of genes associated with lytic infection in HSV-1. Elements surrounding the gene for ICP4 bind a protein, the human neuronal protein Neuronal Restrictive
Silencing Factor (NRSF) or human Repressor Element Silencing Transcription Factor (REST). When bound to the viral DNA elements, histone deacetylation occurs atop the the AI then binds to the The las cell-to-cell signaling

ICP4 gene sequence to prevent initiation of transcription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle. Another HSV transcriptional activator. TheCell-to- system controls the rhl
protein reverses the inhibition of ICP4 protein synthesis. ICP0 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA. The virus can be cell signaling systems are composed cell-to-cell signaling
reactivated by illnesses such as colds and influenza, eczema, emotional and physical stress, exposure to bright sunlight, gastric upset, fatigue or injury, and by of two genes. The I gene encodes an system in a hierarchy
Burn victims who contract P. aeruginosa cascade. The LasR/3-
menstruation. autoinducer synthase and the R gene infections have a high risk of fatality. However,
encodes a transcriptional activator oxo-C12-HSL complex
for burned patients, P. aeruginosa bacteremia activates the
protein (R-protein). The autoinducer has declined as a result of better wound
HSV evades the immune system through interference with MHC class I presentation of antigen on the cell surface. It achieves this through blockade of synthase is responsible for the transcription of rhlR,
the TAP transporter induced by the secretion of ICP-4 by HSV. TAP maintains the integrity of the MHC class I molecule before it is transported via the treatment and dietary changes (removal of raw and 3-oxo-C12-HSL
synthesis of an autoinducer molecule vegetables, which can be contaminated with P.
golgi apparatus for recognition by CD8+ CTLs on the cell surface. ICP-47 disrupts this integrity, preventing the capture of cytosolic proteins for CTL (AI), which crosses the cell blocks the activation
recognition and thus evades CTL destruction. aeruginosa, from the diet). However, P. of RhlR by C4-HSL. The
membrane. With increasing cell- aeruginosa outbreaks in burn units are still
density the intracellular las system itself is
associated with high (60%) death rates. controlled positively
concentration of AI reaches a
threshold level, and complex R- by Vfr and GacA, and
Herpes viruses establish lifelong infections and the virus cannot currently be eradicated from the body. Treatment usually involves general- negatively by RsaL.
purpose antiviral drugs that interfere with viral replication, reducing the physical severity of outbreak-associated lesions and lowering the protein/AI activates the expression of
chance of transmission to others. antivirals such as acyclovir and valacyclovir can reduce reactivation rates. specific target genes.

Trichophyton rubrum Sarcoptes scabiei

Trichophyton are multicelluar fungi with smooth, thin walls. Trichophytono rubrum is a fungus that is the most common cause of athlete’s foot. Athlete’s foot is also
called tinea pedis. This fungus can be found on many locations, including: floors in gyms, locker rooms, swimming pools, nail salons, airport security lines, and in
socks and clothing. The fungus can be spread directly from person-to-person via direct skin-to-skin contact or by contact with these objects. Most people who Sarcoptes is a genus of skin parasites and part of the larger family of mites collectively known as "scab mites". These organisms have 8 legs as
acquire foot fungus have done so by walking barefoot where someone else with foot fungus had previously done so. Some people may be more susceptible to the adults, and are placed in the same phylogenetic class as spiders and ticks. The mites are distributed around the world, equally infecting all ages,
fungus that causes athlete's foot while others are more resistant. The exact cause of this predisposition or susceptibility to fungal infections is unknown. races, and socioeconomic classes in different climates.

This parasite burrows under the host’s skin and causes a contagious skin infection, sabies. Scabies infections occur in humans and animals;
the infection in animals is caused by a different but related mite species. The parasite is tiny and usually not directly visible. When an
When the feet or other areas of the body stay moist, warm, and become irritated, fungus can thrive and infect the upper layers of the skin. Fungal infections can individual has scabies, he or she suffers from intense allergic itching. The disease is usually transmitted via direct skin-to-skin contact,
occur almost anywhere on the body, including the: scalp, trunk, extremities, hands, feet, nails, vagina, mouth, and groin. However, without this moist and warm although it also may be transmitted from objects. Scabies is contagious, and can be spread by scratching an infected area, picking up the
environment, the fungus may not easily infect the skin. Most people with athlete's foot have no symptoms at all and do not even know they have an infection. mites under the fingernails, or through physical contact with someone infected with scabies. Initial infections require two to six weeks to
Many may think they simply have dry skin on the soles of their feet. Common symptoms of athlete's foot typically include various degrees of itching and burning. become symptomatic. Reinfection, however, may manifest symptoms within as little as 24 hours. Because the symptoms are allergic, their
The skin may frequently peel, and in particularly severe cases, there may be some cracking, pain, and bleeding as well. Rarely, athlete's foot can blister. There are delay in onset is often mirrored by a significant delay in relief after the parasites have been eradicated. Crusted scabies, formerly known as
three common types of athlete’s foot: “moccasin type” (soles of the feet), “interdigital type” (in between the toes), and “inflammatory type” (blistering). Norwegian scabies, is a more severe form of the infection often associated with immunosuppression. On those with a weaker immune
system, the host becomes a more fertile breeding ground for the mites, which spread over the host's body, except the face. Sufferers of
crusted scabies exhibit scaly rashes, slight itching, and thick crusts of skin that contain thousands of mites. Such areas make eradication of
mites particularly difficult, as the crusts protect the mites from topical miticides, necessitating prolonged treatment of these areas. The
characteristic symptoms of a scabies infection include intense itching and superficial burrows. The burrow tracks are often linear, with a neat
“line” of four or more closely and equally spaced mosquito-like “bites”. The superficial burrows usually occur on the hands, feet, wrists,
Typical scabies infection. elbows, back, buttocks, and external genitalia. The burrows are created by excavation of the adult mite in the epidermis. Acropustulosis, or
blisters and pustules on the palms and soles of the feet are characteristic symptoms of scabies in infants.
When the skin is injured by the fungus, the natural protective skin barrier is broken, allowing bacteria and yeasts to evade the broken skin, which can cause a secondary
infection. Trichophyton most commonly reproduces asexually through septatic or thin membrane-like hyphae that form reproductive spores.  These spores, called
conidiophores, are constructed “naked” and usually in rows on the conidiospores. Conidiosphores are braches of mycelium. During the first 48 hours of infection, in vitro, the
Trichophyton is undetectable, but is considered to be in its logarithmic phase.  Trichophyton uses a variety of acid proteases, elastases, and keratinases to invade the epidermis Pregnant female mites tunnel into the stratum corneum of a host's skin and deposit eggs in the burrows. The eggs hatch into larvae in 3–10 days. These
or skin cells.  The fungus remains in the stratum corneum of the skin, which is hypothesized why it is so frequent, chronic, and so hard to treat.  The lack of vascularity in this young mites move about on the skin and molt into a “nymphal" stage, before maturing as adults, which live 3–4 weeks in the host's skin. Males roam on top
layer of the epidermis doesn’t allow the immune system to fight effectively once beyond the physical barrier of the skin. of the skin, occasionally burrowing into the skin. In general, there are usually few mites on a healthy hygienic person infested with non-crusted scabies;
approximately 11 females in burrows can be found on such a person. The movement of mites within and on the skin produces an intense itch, which has
the characteristics of a delayed cell-mediated inflammatory response to allergens. IgE antibodies are present in the serum and the site of infection, which
react to multiple protein allergens on the body of the mite. The mite proteins are also present from the gut, in mite feces, which are deposited under the
skin. The allergic reaction is both of the delayed (cell-mediated) and immediate (antibody-mediated) type. Immediate antibody-mediated allergic reactions
have been elicited in infected persons, but not in healthy persons; immediate hypersensitivity of this type is thought to explain the observed far more rapid
Treatment of Trichophyton rubrum can be divided into two parts. The first step is to make the area of infection less suitable for the allergic skin response to re-infection seen in persons having been previously infected. Because the host develops the symptoms as a reaction to the mites' Burrowed Sarcoptes scabiei.
fungus to grow. This means keeping the area clean and dry. Secondly, antifungal creams and washes may be used. Treatment for presence over time, there is usually a 4– to 6-week incubation period after the onset of infestation. Those previously infected with scabies and cured may
athlete's foot should generally be continued for four weeks or at least one week after all of the skin symptoms have cleared. More exhibit the symptoms of a new infection in a much shorter period, as little as 1–4 days.
advanced or resistant cases of athlete's foot may require a two- to three-week course of an oral antifungal. Topical corticosteroid A definitive diagnosis is made by finding either the scabies mites or their eggs and fecal pellets. This involves either scraping a suspected area, mounting
creams can act as a fertilizer for fungus and may actually worsen fungal skin infections. These topical steroid medications have no the sample in potassium hydroxide, and examining it under a microscope, or using dermoscopy to examine the skin directly.
role in treating athlete's foot. If the fungal infection has spread to the toenails, the nails must also be treated to avoid re-infection Crusted scabies infection.
of the feet.

A number of medications are effective in treating scabies including: permethrin (topical; most effective) and ivermectin (oral; treatment of choice for
crusted scabies). There is no vaccine available for scabies.

References: Nir-Paz, R., H. Elinav, G. E. Pierard, D. Walker, A. Maly, M. Shapiro, R. C. Barton, and I. Polacheck. "Deep Infection by Trichophyton Rubrum in an Immunocompromised Patient." Journal of Clinical Microbiology 41.11 (2003): 5298-301.; Department of Biology. "Trichophyton." Trichophyton. 2007. Web. 27 May 2011. <http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/jelahre/index.html>.; Lyczak, Jeffery B., Carolyn L. Cannon, and Gerald B. Pier. "Establishment of Pseudomonas Aeruginosa Infection: Lessons from a Versatile Opportunist." Microbes and Infection 2.9 (2000): 1051-060.; Schaber, J. A ., W. J. Triffo, S. J. Suh, J. W. Oliver, M. C. Hastert, J. A. Griswold, M. Auer, A. N. Hamood, and K. P. Rumbaugh. "Pseudomonas Aeruginosa Forms Biofilms in Acute Infection Independent of Cell-to-Cell Signaling." Infection and Immunity 75.8 (2007): 3715-721.; Arilan, Larry G., James J. Arends, and Majorie S. Morgan. "Immunologic Cross-Reactivity among Various Strains of Sarcoptes Scabiei." The Journal of Parasitology 82.1 (1996): 66-72.; Jones, Clinton. "The Herpes Simplex Virus Type 1 Latency-Associated Transcript Can Protect Neuron-Derived C1300 and Neuro2A Cells from Granzyme B-Induced Apoptosis and CD8 T-Cell Killing." Journal of Virology 85.5 (2011): 2325-332.