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Skin Microflora and Bacterial Infections of the Skin

      The skin is a milieu for controlled bacterial growth. Skin supports the growth of commensal bacteria, which protect the host from pathogenic bacteria. Environmental and local factors, host immunity, and organism adherence and virulence are intricately related to cutaneous infection. Resident gram- positive bacteria include Staphylococcus, Micrococcus, and Corynebacterium sp. Staphylococcus aureus and Strepto coccus pyogenes are notoriously pathogenic in the skin. In order for bacteria to be pathogenic, they must be able to adhere to, grow on, and invade the host. Bacteria possess numerous virulence genes that allow for growth in these privileged niches. Epidermal infections caused by S. aureus and S. pyogenes include impetigo and ecthyma. Dermal infections consist of erysipelas, cellulitis, and necrotizing fasciitis. The pilosebaceous unit is involved in folliculitis, furunculosis, and carbunculosis. Moreover, S. aureus and S. pyogenes produce toxins that may elicit a superantigen response, causing massive release of cytokines. Staphylococcal scalded skin syndrome, toxic shock syndrome, and scarlet fever are all superantigen-mediated. Gram-negative organisms such as Pseudo monas aeruginosa, Pasteurella multocida, Capnocytophaga canimorsus, Bartonella sp., Klebsiella rhinoscleromatis, and Vibrio vulnificus are not typical resident skin microflora but may cause cutaneous infection.

      Keywords

      Abbreviations

      SA
      superantigen
      SE
      skin equivalent

      The skin and host defense mechanisms

      The skin is a barrier that limits invasion and growth of pathogenic bacteria. The cutaneous antimicrobial defense mechanisms include the mechanical rigidity of the stratum corneum and its low moisture content, stratum corneum lipids, production of lysozyme, acidity (pH 5), and defensins (
      • Harder J.
      • Bartels J.
      • Christophers E.
      • Schroder J.M.
      A peptide antibiotic from human skin.
      ). Specifically, most areas of skin are dry, creating an unfavorable environment for bacterial replication. Dead keratinocytes slough and physically remove colonizing bacteria. Skin is cooler than normal body temperature and slightly acidic; most bacteria grow best at a neutral pH and at 37°C. If organisms can evade cutaneous host defenses, the next line of protection involves the inunune system, or skin-associated lymphoid tissue (SALT).

      The skin as a milieu for bacterial growth

      The skin is an intricate habitat for many bacteria. A sterile milieu prenatally, human skin soon becomes host to resident bacteria after birth. The type and density of bacteria are determined by anatomic location, local humidity, the amount of sebum and sweat production, and the host's hormonal status and age (
      • Aly R.
      Cutaneous microbiology.
      ). Bacterial skin flora are commensal, symbiotic, or parasitic relative to the host; although alterations in host immune status are known to have a significant impact, the type of relationship established is often inherent to the bacteria. Persistent colonization is the result of the ability of bacteria to adhere to skin epithelium, grow in a relatively dry and acidic milieu, and rapidly re-adhere during the normal process of desquamation (
      • Feingold D.S.
      Bacterial adherence, colonization, and pathogenicity.
      ).

      Protection by colonizing bacteria

      Skin supports the growth of commensal bacteria, which protect the host from pathogenic bacteria both directly and indirectly. Direct effects include bacteriocin production, production of toxic metabolites, induction of a low reduction oxidation potential, depletion of essential nutrients, prevention of adherence of competing bacteria, inhibition of translocation, and degradation of toxins. Commensal bacteria compete for nutrients, niches, and receptors. For example, Staphylococcus epidermidis bind keratinocyte receptors and inhibit adherence of virulent S. aureus (
      • Bibel D.J.
      • Aly R.
      • Bayles C.
      • Strauss W.G.
      • Shinefield H.R.
      • Maibach H.I.
      Competitive adherence as a mechanism of bacterial interference.
      ). Commensals can release species-specific antibiotic substances known as bacteriocins. For example, S. aureus strain 502A release bacteriocins that inhibit other virulent staphylococcal organisms (
      • Peterson P.K.
      • Verhoef J.
      • Sabath L.D.
      • Quie P.G.
      Extracellular and bacterial factors influencing staphylococcal phagocytosis and killing by human polymorphonuclear leukocytes.
      ). Indirectly, bacteria can induce the host to enhance antibody production, stimulate phagocytosis and clearance mechanisms, and augment interferon and cytokine production. For example, Propionibacterium acnes release fatty acids from lipid breakdown, acidifying the milieu and inhibiting growth of Streptococcus pyogenes (
      • Hentges D.J.
      The anaerobic microflora of the human body.
      ).

      Resident Skin Bacterial Flora (Table I)

      Gram-positive bacteria

      Staphylococcus sp. are gram-positive cocci that aggregate in clusters. Commensal Staphylococcus sp. are distinguished by their inability to produce coagulase, an important virulence-associated enzyme. There are 32 species of coagulase-negative staphylococci, of which 15 are exclusive to humans, and 10 routinely isolated from normal glabrous skin. Staphylococcus epidermidis and S. hominis are the most prevalent coagulase-negative commensals. Occasionally, these organisms cause nosocomial infections in patients with indwelling foreign bodies such as heart valves and intravenous catheters (
      • Archer G.L.
      Staphylococcus epidermidis and other coagulase-negative staphylococcl.
      ).
      Table IBacterial skin residents and their associated dermatoses
      BacteriaLocationDistinguishing featuresSkin pathology
      Gram (+)
      Staphylococcus
      S. epidermidisupper trunkproduce slime
      S. hominisglabrous skin
      S. haemolyticusproduce slime
      S. capitishead
      S. midis
      S. warneri
      S. saprophyticusperineumcause UTI
      S. cohnii
      S. xylosus
      S. simulans
      S. saccharolyticusforehead/antecubitalanaerobic
      Micrococcus
      M. luteus
      M. varians
      M. lylaein children/cold temp
      M. kristinaein children
      M. nishinomiyacnsis
      M. roseus
      M. sedentariuspitted keratolysis
      M. agieis
      Corynebacterium
      C. minutissimumintertriginouslipophilic/porphyrinerythrasma
      C. tenuisintertriginouslipophilictrichomycosis
      C. xerosisconjunctivalipophilicconjunctivitis
      C. jeikeiumintertriginouslipophilic/antibiotic resistant
      Rhodococcuslipophilicgranuloma in HIV
      Propionibacterium
      P. acnessebaceous glandlipophilic/anaerobicacne
      P. granulosumsebaceous glandlipophilic/anaerobicsevere acne
      P. avidumaxillalipophilic/anaerobic
      Brevibacteriumtoe websnonlipophilic (large-colony)foot odor, white piedra
      Dermabacternonlipophilic (large-colony)pitted keratolysis
      Gram (–)
      Acinetobacterdry areasgram-negativeburn wounds
      Micrococcus sp. are also gram-positive cocci, distinguished from staphylococci by the inability to produce acid anaerobically from glycerol. Moreover, Micrococcus sp. are not lysed by lysostaphin and nitrofuran. At least eight species have been isolated from human skin, the most common being M. luteus.
      Coryneforms are gram-positive pleomorphic bacilli. Skin commensals include Corynebacterium sp., Propionibacterium sp., Dermabacter sp., and Brevibacterium sp. Corynebacteria are classified as either lipophilic or nonlipophilic. Lipophilic organisms colonize areas rich in lipids or sebum such as the axilla and include Arcanobacterium haemolyticum, C. xerosis, C. minutissimum, and C. striatus. These organisms do not produce toxins and are nonmotile. Propionibacterium acnes is the dominant anaerobic coryneform on the skin. Unlike most commensals, its anaerobic requirements favor growth deep in adnexal structures as opposed to squamous epithelium. Dermabacter and Brevibacterium sp. prefer glabrous, humid skin such as the toewebs. The production of methane thiol by Brevibacterium sp. is the cause of “foot odor”.

      Gram-negative bacteria

      Gram-negative organisms do not normally reside in the dry environment of normal skin. Occasionally, moist intertriginous areas allow for the growth of Acinetobacter sp.

      Pathogenicity and virulence factors

      For an organism to become a pathogen, it must be able to circumvent normal host defense mechanisms. Perhaps the best-studied cutaneous pathogen is S. aureus, yet relatively little is known regarding the pathogenic mechanisms employed. Staphylococcus aureus readily adheres to all mammalian cell types, including keratinocytes (
      • Bibel D.J.
      • Aly R.
      • Shinefield H.R.
      • Maibach H.I.
      The Staphylococcus aureus receptor for fibronectin.
      ;
      • Ogawa S.K.
      • Yurberg E.R.
      • Hatcher V.R.
      • Levitt M.A.
      • Lowy F.D.
      Bacterial adherence to human endothelial cells in vitro.
      ;
      • Cole G.W.
      • Silverberg N.L.
      The adherence of Staphylococcus aureus to human comeocytes.
      ; Murakawa, unpublished data). Teichoic acids mediate the binding of S. aureus to nasal epithelial cells as well as to fibronectin. Staphylococcus aureus binds most efficiently to well-differentiated keratinizing cells, and there is an increased affinity for keratinocytes derived from patients with atopic dermatitis (
      • Cole G.W.
      • Silverberg N.L.
      The adherence of Staphylococcus aureus to human comeocytes.
      ).
      Several S. aureus virulence genes have been identified, including numerous surface and extracellular proteins at the end of exponential growth (
      • Foster T.J.
      • McDevitt D.
      Surface-associated proteins of Staphylococcus aureus: their possible roles in virulence.
      ). Expression of virulence genes is controlled by global regulatory elements, including sar, agr, xpr (
      • Cheung A.L.
      • Wolz C.
      • Yeaman M.R.
      • Bayer A.S.
      Insertional inactivation of a chromosomal locus that modulates expression of potential virulence determinants in Staphylococcus aureus.
      ). Adherence to extracellular matrix proteins is mediated by MSCRAMM (microbial surface components recognizing adhesive matrix molecules) (
      • Patti J.M.
      • Allen B.L.
      • McGavin M.J.
      • Hook M.
      MSCRAMM-mediated adherence of microorganisms to host tissues.
      ). Other S. aureus virulence factors include catalase, hyaluronidase, and β-lactamase.
      Our laboratory is investigating the interactions of S. aureus with keratinocytes and other components of the skin. Staphylococcus aureus is an ideal cutaneous pathogen to study because of its clinical relevance, well-delineated genome, and ability to grow on both liquid and solid media. Using plate assays, we have characterized the ability of S. aureus to adhere to, invade into, and grow on mammalian cells. Adherence assays are performed by incubating bacteria with mammalian cells, washing with PBS to remove nonadherent bacteria, and lysing the mammalian cells to free adherent or intracellular bacteria. Subsequently, the bacteria are diluted, plated, and counted to determine adherence. Intracellular bacteria are identified similarly, except that prior to lysing, the samples are treated with lysostaphin, a cytotoxic agent that specifically targets all extracellular bacteria. Using these assays, we have shown that S. aureus adhere to all mammalian cells (including macrophages and keratinocytes) efficiently and immediately (20%-60% within 15 min). Additionally, S. aureus invade macrophages efficiently and immediately (20%-50% in 30 min), but invade keratinocytes poorly (1%-4% in 4 h) (Figure 1). Morphologic studies using light and electron microscopy have confirmed these results, and intracellular bacteria reside within vacuoles.
      Figure thumbnail gr1
      Figure 1Invasion and adherence assays using S. aureus with mammalian cells. (A) Macrophage adherence; (B) macrophage invasion; (C) keratinocyte adherence; (D) keratinocyte invasion. As shown in (A) and (B), S. aureus adhere to macrophages and keratinocytes efficiently and immediately (20%-60%) within 15 min. As shown in (C) and (D), S. aureus invades macrophages efficiently and immediately (20–50%) within 30 min, but invade keratinocytes poorly (1%-4% in 4 h).
      We have further characterized the interactions of S. aureus with skin by using skin equivalents (SE). Collagen and fibroblasts are combined to form a dermal matrix, and keratinocytes are subsequently added atop the matrix and allowed to differentiate, forming the SE. Bacteria readily adhere to and grow on the SE, but do not penetrate deeply into the epidermis or dermis (data not shown).

      Infections caused by s. aureus and s. pyogenes

      Staphylococcus aureus is the most common cause of cutaneous and systemic infections. It may transiently colonize the skin of newborn infants, the anterior nares in 20%-40% of healthy individuals, and the skin of atopic patients (
      • Strange P.
      • Skov L.
      • Lisby S.
      • Nielsen P.L.
      • Baadsgaard O.
      Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis.
      ). Staphylococcus aureus is the most common cutaneous bacterial pathogen in HIV-infected patients, causing superficial and deep dermal pathology that can lead to life-threatening complications (
      • Berger T.G.
      Treatment of bacterial, fungal, and parasitic infections in the HIV-infected host.
      ). In part, the susceptibility of HIV-infected patients to S. aureus may be a consequence of ongoing and increased nasal carriage of this organism. Recurrence after therapy is extremely common.
      As with S. aureus, Streptococcus sp. are notoriously pathogenic in the skin. Streptococcus Groups A, B, C, D, and G (based on the Lancefield classification that segregates Streptococcus sp. according to M-protein serotype) are frequent human pathogens. M-protein is a virulence antigen that confers bacterial resistance to phagocytosis. Streptococcus pyogenes is not typically a cutaneous resident, but is asymptomatically carried in the throat of 15% of school-aged children (
      • Bisno A.L.
      Streptococcus pyogenes.
      ).
      Table II lists the cutaneous infections caused by S. aureus and S. pyogenes.
      Table IIStaphylococcus aureus and S. pyogenes skin infections
      InfectionsS. aureusS. pyogenes
      Epidermal
       Impetigo+++++
       Ecthyma++++
      Dermal
       Erysipelas++++
       Cellulitis+++++
       Necrotizing fasciitis+++
      Follicular
       Folliculitis++++
       Furunculosis++++
       Carbunculosis++++
      Other
       Paronychia++++
       Blistering distal dactylitis++++
       Botryomycosis+++
       Mastitis+

      Epidermal infections – impetigo and ecthyma

      Impetigo, the most common bacterial infection in children, is a highly communicable, superficial infection caused by either S. aureus or S. pyogenes (
      • Wannamaker L.W.
      Differences between streptococcal infections of the throat and of the skin.
      ). Non-bullous impetigo typically occurs on the face or extremities following minor cutaneous trauma. Erythematous papules, pustules, or vesicles develop into erosions covered by characteristic honey-colored crust. Lesions are usually painless, and there may be associated lymphadenopathy and leukocytosis. Cellulitis, lymphadenitis, scarlet fever, and guttate psoriasis are rare sequelae. Bullous impetigo is characterized by flaccid bullae that rupture easily, leaving a thin collarette of scale. There is usually no associated lymphadenopathy. Bullous impetigo is mediated by exfoliative toxin, which also causes staphylococcal scalded-skin syndrome (SSSS).
      Ecthyma is a deeper form of impetigo in which ulcerations form beneath crusted plaques. The lower extremity is the most common site of involvement, and scarring is common. Streptococcus pyogenes or S. aureus are the usual culprits.

      Dermal infections – erysipelas, cellulitis, necrotizing fasciitis

      Erysipelas is an acute infection caused by S. pyogenes involving the dermis and dermal lymphatics (
      • Jorup-Ronstrom C.
      Epidemiological, bacteriological and complicating features of erysipelas.
      ). Sharply demarcated, tender, erythematous plaques with an elevated advancing border occur on the lower extremities or face following an inflammatory dermatosis or traumatic insult. Vesicles and bullae may develop, resulting in local gangrene. Lesional cultures are usually negative. Constitutional symptoms and leukocytosis are common. A devastating complication of erysipelas is cavernous sinus thrombosis (
      • Wortman P.D.
      Bacterial infections of the skin.
      ).
      Cellulitis, unlike erysipelas, involves the subcutaneous tissue, and is caused by S. pyogenes or S. aureus (
      • Hook E.W.
      • Hooton T.M.
      • Horton C.A.
      • Coyle M.B.
      • Ramsey P.G.
      • Turck M.
      Microbiologic evaluation of cutaneous cellulitis in adults.
      ). There is usually a background of chronic edema and stasis dermatitis, and tinea pedis is most common portal of entry associated with leg cellulitis. The edematous, warm plaques of cellulitis are poorly demarcated, and lymphangitis occurs less frequently than with erysipelas. Constitutional symptoms are mild, and the causative organism is difficult to isolate. Local abscesses, necrotizing fasciitis, and septicemia may occur.
      Two forms of cellulitis occurring in children deserve special mention. Perianal cellulitis caused by S. pyogenes presents in young children as perianal erythema, which may be associated with painful defecation and blood-tinged stool (
      • Barzilai A.
      • Choen H.A.
      Isolation of group A streptococci from children with perianal cellulitis and from their siblings.
      ). Perianal cellulitis may be a trigger for guttate psoriasis. Haemophilus influenzae, a gram-negative rod, causes a facial cellulitis in children 3 mo to 4 y of age characterized by violaceous, indurated plaques. Meningitis is a feared complication. The advent of the H. influenzae vaccine has dramatically reduced the incidence of this form of cellulitis.
      Necrotizing fasciitis is a potentially life-threatening infection of the subcutaneous fascia (
      • Tharakaram S.
      • Keczkes K.
      Necrotizing fasciitis. a report of five patients.
      ). Within 48 h, erythema, pain, and edema progress to violaceous, dusky plaques that quickly necrose. Anesthesia of the involved skin is characteristic. The most common cause is S. pyogenes, but S. aureus, coliforms, enterococci, Pseudomonas sp., and Bacteroides sp. have also been culprits.

      Follicular infections – folliculitis, furunculosis, carbuncu losis

      Infections of the hair follicle or pilosebaceous unit are classified as either superficial or deep (
      • Wortman P.D.
      Bacterial infections of the skin.
      ). Folliculitis, caused by S. aureus, is characterized by discrete, follicular-based pustules. Carriage of S. aureus in the nares may lead to sycosis barbae in young men, presenting as inflammatory plaques in the beard area.
      Deeper infections of hair follicle can lead to furuncles or carbuncles. A furuncle, or boil, is a nodule in a hair-bearing area that discharges purulent, necrotic debris. Carbuncles are multiple furuncles that coalesce to form large, deep, interconnected abscesses. Staphylococcus aureus is the cause in nearly all cases.

      Miscellaneous infections

      Acute paronychia, caused by S. aureus, presents as purulent tender swellings of the nailfold (
      • Brook I.
      Bacteriologic study of paronychia in children.
      ). Blistering distal dactylitis, caused by S. pyogenes and occasionally S. aureus, is characterized by tense blisters on an erythematous base over the volar fat pad of the phalanx of a finger (
      • McCray M.K.
      • Esterly N.B.
      Blistering distal dactylitis.
      ). Botryomycosis is a granulomatous and suppurative infection caused by S. aureus, presenting on the lower extremity as crusted granulomatous plaques, ulcers, and sinus tracts draining purulent material.

      Toxin-Mediated S. Aureus and S. Pyogenes Syndromes (Table III)

      Staphylococcus aureus and S. pyogenes produce several toxins that can cause localized destruction or systemic symptoms (
      • Hackett S.P.
      • Stevens D.L.
      Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis.
      ). Systemic symptoms are mediated by superantigens (SA). Conventional antigens are expressed on the cell surface of antigen-presenting cells in association with the major histocompatibility type II complex (MHC II). Interaction with the T cell receptor occurs in a very specific, antigen-restricted fashion. Superantigens circumvent this process, interacting directly with a portion of the MHC II complex and with only the V-β section of the T cell receptor, without antigen (
      • Rosen H.
      Superantigens.
      ). Large-scale T cell activation leads to the massive release of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) (
      • Jupin C.
      • Anderson S.
      • Damais C.
      • Alouf J.E.
      • Parant M.
      Toxic shock syndrome toxin 1 as an inducer of human turnor necrosis factors and gamma-interferon.
      ). These cytokines lead to the clinical findings of fever, emesis, erythematous rash, hypotension, tissue injury, and shock. Physical signs common in toxin-induced staphylococcal and streptococcal syndromes include strawberry tongue, acral erythema with subsequent desquamation, and perineal erythema.
      Table IIIStreptococcus pyogenes and S. aureus toxins
      For further details, seeManders (1998).
      DiseaseOrganismToxin
      SSSSS. aureusExfolative toxin A
      Exfoliative toxin B
      Bullous impetigoS. aureusExfoliative toxin A
      Exfoliative toxin B
      TSSS. aureusTSST-1
      TSSS. pyogenesSPE-A
      SPE-B
      SPE-C
      Streptococcal superantigen
      Mitogenic factor
      Scarlet feverS. pyogenesSPE-B
      SPE-C
      a For further details, see
      • Manders S.M.
      Toxin-mediated streptococcal and staphylococcal disease.
      .
      SSSS, most commonly seen in infants, presents with a prodrome of fever, skin tenderness, and erythema localized primarily to flexural areas (
      • Resnick S.D.
      Staphylococcal toxin-mediated syndromes in childhood.
      ). There is sparing of the palms, soles, and mucous membranes. Generalized exfoliation quickly ensues, and the Nikolsky's sign is positive. Group 2 S. aureus, most commonly phage type 71, can be isolated from mucous membranes (skin erythema and desquamation are due to remote effects of the toxin). Exfoliative toxins A and B (ETA and ETB) have been implicated in the pathogenesis of SSSS, along with δ-hemolysin (
      • Manders S.M.
      Toxin-mediated streptococcal and staphylococcal disease.
      ).
      Toxic shock syndrome (TSS) is a multisystern illness caused by S. aureus or S. pyogenes. Clinically, diffuse macular erythema is followed by desquamation, especially of palms and soles. Staphylococcal TSS is typically associated with tampon use (
      • Shands K.N.
      • Schmid G.P.
      • Dan B.B.
      • et al.
      Toxic-shock syndrome in menstruating women. association with tampon use and Staphylococcus aureus and clinical features in 52 cases.
      ). Cases associated with S. pyogenes usually involve a soft-tissue infection. Most cases of staphylococcal TSS are mediated by TSST-1, although S. aureus strains expressing entero toxins B and C (SEB, SEC) have been isolated. Streptococcal TSS is primarily associated with SPE-A, although SPE-B, SPE-C, streptococcal superantigen, and mitogenic factor have been occasional culprits (
      • Manders S.M.
      Toxin-mediated streptococcal and staphylococcal disease.
      ).
      Scarlet fever, caused by S. pyogenes, occurs shortly after an episode of pharyngitis and is characterized by a papular erythematous “sandpaper” rash on the trunk and extremities accompanied by perioral pallor (
      • Stevens D.L.
      Invasive group A streptococcus infections.
      ). A linear petechial eruption (Pastia's lines) occurs in flexural areas. A white coating on the tongue with hypertrophied projecting papilla leads to the so-called “white strawberry tongue”. Currently, SPE-B and SPE-C are the toxins most frequently isolated. Staphylococcal scarletina mimics classic scarlet fever, but the strawberry tongue is not seen.

      Other gram-positive bacterial skin infections

      Corynebacteria are normally found in intertriginous areas, where growth is enhanced by hyperhidrosis. Erythrasma, caused by C. minutissimum, is characterized by sharply defined, brown, slightly scaling plaques in intertriginous areas (
      • Sindhuphak W.
      • MacDonald E.
      • Smith E.B.
      Erythrasma.
      ). Characteristic coral-red fluorescence is due the production of porphyrin. Pitted keratolysis presents as discrete coalescing crater-like pits on the plantar surface of the feet. In trichomycosis axillaris, concretions on axillary or pubic hair shafts occur.
      Erysipelothrix rhusiopathiae is a gram-positive aerobic bacillus that causes erysipeloid, a localized cellulitis typically on the hands (
      • Barnett J.H.
      Erysipeloid.
      ). Clinical findings include bright-red or violaceous, well-demarcated, polygonal plaques, often with central clearing. Erysipelothrix rhusiopathiae is present on dead matter of animal origin. Infection following trauma is seen in fish, meat, and poultry handlers, as well as farmers.
      Bacillus anthracis is a nonmotile, gram positive aerobic rod that is capable of forming spores, and can produce both a localized cutaneous and a systemic infection (
      • Dixon T.C.
      • Meselson M.
      • Guillemin J.
      • Hanna P.C.
      Anthrax.
      ). Cutaneous anthrax accounts for 95% of all anthrax infections in the USA, and typically develops in patients with a history of occupational contact with animals or animal products.

      Gram-negative bacterial skin infections

      An atypical form of cellulitis occurring in HIV-infected patients is caused by Helicobacter cinaedi (
      • Sullivan A.K.
      • Nelson M.R.
      • Walsh J.
      • Gazzard B.G.
      Recurrent Helicobacter cinaedi cellulitis and bacteremia in a patient with HIV infection.
      ). Red-brown or copper plaques with minimal warmth are characteristic. The cellulitis may be multifocal and recurrent.
      Pseudomonas aeruginosa is an aerobic gram-negative rod found in moist environments. Ecthyma gangrenosum occurs primarily in immunosuppressed patients in the setting of Pseudomonas sepsis (
      • Baze P.
      • Thyss A.
      • Caldani C.
      • Julilin L.
      • Schnelder M.
      • Ortonne J.P.
      P. aeruginosa 0–11 folliculitis.
      ). Hemorrhagic bullae progress to deep ulcerations with eschar. “Hot tub” folliculitis presents as pruritic, discrete erythematous papules and pustules on the trunk and buttocks 8–48 h after water immersion. It is a self-limited disease resolving within 7–10 d; however, immunocompromised patients may develop ecthyma gangrenosum. Other diseases caused by P. aeruginosa include gram-negative toe web infections and green nail syndrome. Pseudomonas aeruginosa is also an important cause of morbidity and mortality in burn victims.
      Pasteurella multocida is a gram-negative coccobacillus that is part of the commensal flora in dogs and cats (
      • Griego R.D.
      • Rosen T.
      • Orengo I.F.
      • Wolf J.E.
      Dog, cat, and human bites: a review.
      ). Following an animal bite, a rapidly progressive cellulitis with gray-colored serous drainage develops. Local complications including septic arthritis are common.
      Bartonella sp. are aerobic, fastidious gram-negative bacteria. Bartonella henselae causes cat scratch disease (CSD) and bacillary angiomatosis (BA), B. quintana causes trench fever and BA, and B. bacilliformis causes verruga peruana and Oroya fever. CSD develops at the site of trauma, usually in the head and neck area, and is associated with unilateral lymphadenopathy. BA and verruga peruana are characterized by vascular skin lesions resembling pyogenic granulomas. Patients with trench fever and Oroya fever present with systemic symptoms but no cutaneous lesions (
      • Murakawa G.J.
      • Berger T.
      Bartonellosis.
      ).
      Capnocytophaga canimorsus, formerly referred to as DF-2, is a gram-negative rod that is commensal flora of dog and cats. Human infection is characterized by necrotizing eschar at the site of the bite. Alcoholics and patients who have undergone splenectomy are particularly predisposed to severe septicemia following the bite (
      • Herbst J.S.
      • Raffanti S.
      • Pathy A.
      • Zaiac M.N.
      Dysgonic fermenter type 2 septicemia with purpura fulminans.
      ).
      Rhinoscleroma is a granulomatous infection of the nasal mucosa and surrounding tissues caused by Klebsiella rhinoscleromatis (
      • Andraca R.
      • Edson R.S.
      • Kern E.B.
      Rhinoscleroma: a growing concern in the United States? Mayo Clinic experience.
      ). Patients present with infiltrative and destructive granulomatous plaques that may lead to life-threatening complications. Transmission is by nasal secretions.
      Consumption of raw seafood or seawater exposure may lead to infection with Vibrio vulnificus (
      • Hlady W.G.
      • Mullen R.C.
      • Hopkins R.S.
      Vibrio vulnificus from raw oysters.
      ). Erythematous, indurated plaques studded with hemorrhagic bullae, pustules, petechiae, and areas of gangrene are found on the lower extremities.
      In summary, the skin is a poor media for bacteria given the large number of inherent defense mechanisms; however, when altered or breached or under moist occlusive conditions, the skin can support the growth of both commensal and pathogenic bacteria. Although the bacteria–host interactions have been studied in depth, much remains unknown regarding the pathogenic mechanisms that bacteria employ and the host defense mechanisms to counteract infections.

      ACKNOWLEDGMENTS

      Dr. Murakawa was supported by the Howard Hughes Medical Institute, Dermatology Foundation Research Grant and National Institute of Arthritis, Musculoskeletal and Skin Diseases K-08 AR02068-02.

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