Chapter 4 Biofilms in Health and Medicine
Section 8 The Flora of the Major Body Systems
Page 2 The Skin

The flora of the major body systems

The skin

The skin is the largest organ in the human body.  In a mature adult it may represent a surface area of 1.75 m2 (Wilson, 2005).  It is perhaps the most ecologically variable tissue of the body varying from roughened dry areas with desert-like moisture levels (elbows) to moist, mucus-covered regions more reminiscent of a salty pool or a tropical rain forest (conjunctiva, lips).  Dead cells of the epithelium are constantly being shed, taking with them a burden of surface colonizing microbes.These are replaced by mitotic division of the basal epithelium in a succession that takes about one month from mitosis to desquamation (Jakubovic and Ackerman, 1992).  Bacterial cells principally inhabit a stratified layer of epithelium about 3 cell layers thick.  The superficial cells of this colonized region are being constantly sloughed off (desquamated). Persistence of the microbial population requires a continuous process of cell division and invasion of newly available cells from below.

Perhaps the most heavily colonized dermal structures are the hair follicles and their associated sebaceous glands.  Due to their opening to the surface, their abundant nutrient sources and their protection from abrasion and desquamation hair follicles may develop.

One may consider the microbial population of the skin as a biofilm in which water is the limiting factor.

The most common microbial representatives of the skin are the “coagulase negative staphylococci, lipophilic and nonlipophilicdiphtheroids, and yeasts with a few gram negative species in some sites” (Marples, 1994).

The numbers of bacteria differ dramatically from one part of the integument surface to another. 

Sebaceous glands of the skin, particularly the face and scalp, secrete compounds such as sebum, an oily material, which prevents the skin from drying out.  The saturated and unsaturated fatty acids in sebum are somewhat inhibitory to growth of bacterial, particularly gram positive bacteria such as S. aureus. Sweatcontainslysozyme, an enzyme that cleaves cross linkages in bacterial cell walls, particularly of Gram + cells.  Constant shedding, these materials and the low pH of the skin surface restrict the number and array of bacteria that can colonize and flourish on the skin.  Among those organisms adapted to growth on the skin are the coagulase negative Gram positivecocci such as S. epidermidis, the micrococci, various corynebacteria, the propionibacteria and some lactobacilli and yeasts.

Many of these endemic bacteria are capable of causing disease in individuals who are immune compromised or who have temporary or permanent medical devices.  Corynebacteriumurealyticum for example may cause urinary tract infections in patients with long term catheterization.  The anaerobic propionibacteria (e.g. P. acnes) is the causal agent of acne, but is also found as a component of biofilms infecting implanted devices and wounds.  The staphylococci of the skin are quite variable and many species have been identified among the normal flora of the skin.  These are typically divided into two major groups according to their production of the virulence factor enzyme coagulase.  Coagulase positive species such as S. aureus are capable of coagulating blood serum while coagulase negative species such as S. epidermidis, do not.

The skin acts as the primary barrier to infection, constantly renewing itself and repairing the many injuries, minor and more serious to which the human organism is prone.  One can appreciate the effectiveness of the skin as a barrier to disease by examining data on the frequency of major infectious disease in victims of burns or “road rash” or by a study of the relative resistance to superficial infections experienced by immune deficient or immune suppressed individuals whose intrinsic immunity is severely compromised.  Given their extreme susceptibility to infection , the fact that they survive for extended periods is a testament to the effectiveness of the skin in excluding pathogens.

Antimicrobial defense mechanisms of the skin

The stratified and keratinized cells of the skin’s surface surrounded by lipid-rich materials serve as barrier to the colonization of skin by transient microorganisms.  The lipid-like materials include fatty acids, triglycerides, sterols, ceramides, squalene phospholipids and others.  Some of these, lauric acid and myristic acid for example,  are known to have antibacterial properties.  Most of the skin surface is quite dry, a fact which renders skin a difficult substratum for most organisms to establish themselves.  In addition the low pH of the skin which varies from 4.8 to 6.2 depending on location is inhibitory to many potential colonizers.  Evaporation of sweat, leaves behind a residue of solutes including sodium chloride which has an osmotic effect on most bacterial inhibiting growth. 

Other materials, products of the bodies innate defense mechanisms are also present on skin.  These include a variety of peptides with antimicrobial properties such as human βdefensin and adrenomedullin which exhibit bactericidal effectiveness against Gram positive and Gram negative bacteria, fungi and viruses.

Lysozyme is also found in relatively high concentrations on the skin surface.  This enzyme causes degradation of the peptidoglycan layer of the Gram positive cell wall by causing breaks in the oligo-peptide cross linkages which join the many polysaccharide stands which constitute the bacterial cell wall. 

The problems encountered in disinfecting skin

It is commonly believed among medical professionals that the disinfection of skin prior to surgery or transdermal injection is a successful strategy for making the target site microbiologically safe for these invasive procedures.Support for this contention comes from experiments in which swabs of disinfected skin are shown to be “sterile” when spread on nutrient medium plates.  Other experiments, however, in which rabbit skin, disinfected with iodine is macerated and plated reveal that as many as 1 x 105 cells/ cm2 of Streptococcusnepalensis may be cultured (Costerton, the Biofilm Primer p 108).  Direct microscopic observation of human skin reveals S. epidermidis growing at depths of as much as 5 cell layers in dry skin and as much as 20 skin cell layers in areas surrounding surgical openings or stoma (Costerton, the Biofilm Primer p 108).  It would appear that disinfectant preparation of the skin is rather effective at removing the transient microbial population and perhaps the most superficial resident cells from the prepared area, but is ineffective in removing cells of the resident population at depth.

“Therefore when a medical device is placed across prepared skin, the living bacteria in the integrated population will inevitably form biofilms on its surface” (Costerton 2007 [Primer]).

The Effectiveness of Proper Skin Cleansing

The importance of washing the hands to prevent transmission of pathogens (or cadaverous material) has been known since the investigations of IgnazSemmelweis, an obstetric physician in Vienna in 1847-48. Perplexed and dismayed by the fact that new mothers died at a rate of 7-15% in the medical school portion of the Vienna General Hospital, and at a much lower rate in the portion of the hospital dedicated to the training of midwives he set out to find the cause.  Eventually, realizing that the critical difference was that doctors in training performed autopsies while midwives did not, he instituted the practice of hand washing with bichloride of lime among the doctors on his service.  Following the imposition of the hand-washing regimen, the frequency of deaths due to “child bed” or “puerperal fever” declined by 90%.  The medical community was not ready for the ideas and techniques initiated by Semmelweis and their reluctance to adopt his procedures with its resultant burden of maternal mortality increased his anger and some maintain deranged his mind.  Semmelwise was committed to a mental institution in 1865.  He died shortly thereafter a martyr to the progress of medical science.  To give the medical establishment the benefit of a great deal of doubt, there was at the time no mechanism that Semmelwise could point to support his hypotheses.  The germ theory of disease, which accounted for his observations and the success of his techniques would not be formulated by Pasteur, Koch and others for several decades.

More recently concern has arisen with regard to the relationship between skin hygiene and the transmission of disease.  Some studies indicate that frequent handwashing, especially with soaps, detergents and other agents that may damage skin can actually increase the resident bacterial population and the probability of pathogen transmission. 

Public health policy on how best to protect the public at large and as consumers of health services lags behind scientific understanding of the risks inherent in hand washing and in the use of antibacterial agents.  Many studies support the contention that hand washing properly performed, reduces the bacterial count on the skin and the incidence of disease transmission.  This knowledge is of little practical value, however, because the public at large wash too infrequently and for much too short a time to effect adequate cleansing.

In 2003, a study of hand washing habits in airport restrooms was conducted by Wirthlin Worldwide, political and business consulting firm. This study revealed that despite recent outbreaks of gastrointestinal and respiratory infection, as many as 30% of people failed to wash their hands after using the restroom facilities in several major UA airports including JKK in New York, O’Hare in Chicago and Miami Dade in Florida.  In general, men were less likely to wash their hands in restrooms than women (74% vs. 83%).  In another Wirthlin study 95% of 6,333 respondents reported always washing their hands while direct observation indicated that, in fact, only 67% actually did so.

Hand washing recommendations from the Harvard Medical school explain that washing hands with soap and warm water for 15 seconds or about the time it takes to sing “Happy birthday to you” will reduce the number of surface bacteria on hands by 90%.

Recommendations for washing hands include:

It has been suggested that the use of antimicrobic hand washing products should be encouraged as these have been shown to effectively reduce the number of transient and resident organisms on the skin.  But, some studies indicate that the use of products containing agents like triclosan select for resistance among surviving organisms.  In fact some of the organisms newly resistant to triclosan were also resistant to some antibiotics as well.  In light of the uncertainty in the scientific data the public would probably be well advised to confine their use of cleansing agents to soaps and detergents and the use of alcohol based antiseptic cleansers which are not known to select for resistance.