Human skin is an important part of the innate immune system. In addition to serving a wide range of other functions, the skin serves as an important barrier to microbial invasion. Not only is it a physical barrier to penetration of deeper tissues by potential pathogens, but it also provides an inhospitable environment for the growth of many pathogens. In this section, we will provide a brief overview of the anatomy and normal microbiota of the skin and eyes, along with general symptoms associated with skin and eye infections.

A microbiome is all of the genetic material found within an individual microbe such as a bacterium, fungal cell, or virus. It also may refer to the collection of genetic material found in a community of microbes that live together.

Microbiome. Microbes are the small organisms that we can just barely see under a microscope, like bacteria, fungi, viruses... And these microbes live everywhere. They live in the soil, they live in the water, and they live in and on our body. The microbiome is a new term that refers to all of the genetic material found in an individual microbe such as one of these bacteria or fungi or viruses. So if we think about the entire DNA sequence of a microbe, that is the microbiome.

Did you know that your body contains many more microbes (including bacteria and viruses) than human cells? And, even though some microbes can cause dangerous infections, you can't live without others? Viral and bacterial genomes might be small, but they are packed with information and some surprises about evolution and human health.

When you think of bacteria or viruses, what comes to mind? If you've been sick recently, you might not have good thoughts about them.

In 2018, infections from the influenza virus have been particularly rough. A big difference between 2018 and 15 years ago when the Human Genome Project was completed, is that genomics is now used routinely to track influenza virus infections, in real time, as the virus spreads across the country. These data are used to help design the vaccine used for our annual "flu shot." Even so, just one mutation in the virus's genome can make a big difference in the severity of someone's infection. Beyond influenza, the most advanced genomics technologies are being used to track infections caused by the Ebola and Zika viruses as they spread and mutate.

You may have also heard of situations where the overuse of antibiotics in both the medical and agricultural fields has contributed to bacteria becoming resistant to antibiotics, because with more exposure, bacteria that spontaneously develop resistance survive and reproduce more in this new environment, spreading this trait to the next generation. Now that we can track various microbes' genome sequences very accurately, we can see that antibiotic resistance most often happens when bacteria trade their DNA back and forth transferring the resistance trait. DNA sequencing of many, many bacterial species has now shown us that there has been rampant transfer of genes throughout history from early species of bacteria to those in existence today. These findings should make people think about the overuse of antibiotics in our world, since in the most extreme cases of infection with antibiotic-resistant bacteria can lead to serious illness and even death.

Microbes Make You Who You Are

Besides the microbes that make you ill, there are also "good" microbes. We contain multitudes of microbes (bacteria, yeast, and viruses), called our "microbiome." We would not be able to properly digest food without them living in our gut, or to have a working immune system without regular exposure to these microbes. However, things can also go wrong with your gut microbiome, such as when infection with the bacterium H. pylori leads to ulcers - this discovery led to the Nobel Prize in 2005. But, for the most part, our gut bacteria are huge helpers; they even train our own immune systems on what is "good" and what is "bad" in the microbial world. In another story related to our microbiome, we acquire millions of microbes from our mother at birth, including ones that live in our throats and quickly spread to keep out other, more harmful species. Genome sequencing has shown us how diverse our microbial communities are, and we will learn even more as the NIH's Human Microbiome Project finishes its work in 2018.

We Can Engineer New Microbes

Now that we have learned so much about microbial genomics, what else can we do? The field of synthetic biology has emerged directly from advances in DNA sequencing technologies, allowing for the design and construction of new biological systems. Teams from around the world are manipulating microbial genomes for applications in energy production and medicine. There is even the International Genetically Engineered Machine Competition (or iGEM) in which thousands of students compete each year to build new systems using standard parts called BioBricks. In 2016, a winning high school team from Taiwan constructed a new strain of E. coli, a famous bacterium that lives in your gut, that can detect levels of poisonous metals in Chinese medicines.

Human skin is made up of several layers and sublayers. The two main layers are the epidermis and the dermis. These layers cover a third layer of tissue called the hypodermis, which consists of fibrous and adipose connective tissue (Figure 21.2).

The epidermis is the outermost layer of the skin, and it is relatively thin. The exterior surface of the epidermis, called the stratum corneum, primarily consists of dead skin cells. This layer of dead cells limits direct contact between the outside world and live cells. The stratum corneum is rich in keratin, a tough, fibrous protein that is also found in hair and nails. Keratin helps make the outer surface of the skin relatively tough and waterproof. It also helps to keep the surface of the skin dry, which reduces microbial growth. However, some microbes are still able to live on the surface of the skin, and some of these can be shed with dead skin cells in the process of desquamation, which is the shedding and peeling of skin that occurs as a normal process but that may be accelerated when infection is present.

Beneath the epidermis lies a thicker skin layer called the dermis. The dermis contains connective tissue and embedded structures such as blood vessels, nerves, and muscles. Structures called hair follicles (from which hair grows) are located within the dermis, even though much of their structure consists of epidermal tissue. The dermis also contains the two major types of glands found in human skin: sweat glands (tubular glands that produce sweat) and sebaceous glands (which are associated with hair follicles and produce sebum, a lipid-rich substance containing proteins and minerals).

Perspiration (sweat) provides some moisture to the epidermis, which can increase the potential for microbial growth. For this reason, more microbes are found on the regions of the skin that produce the most sweat, such as the skin of the underarms and groin. However, in addition to water, sweat also contains substances that inhibit microbial growth, such as salts, lysozyme, and antimicrobial peptides. Sebum also serves to protect the skin and reduce water loss. Although some of the lipids and fatty acids in sebum inhibit microbial growth, sebum contains compounds that provide nutrition for certain microbes.

Figure 21.2 (a) A micrograph of a section through human skin shows the epidermis and dermis. (b) The major layers of human skin are the epidermis, dermis, and hypodermis. (credit b: modification of work by National Cancer Institute)

The skin is home to a wide variety of normal microbiota, consisting of commensal organisms that derive nutrition from skin cells and secretions such as sweat and sebum. The normal microbiota of skin tends to inhibit transient-microbe colonization by producing antimicrobial substances and outcompeting other microbes that land on the surface of the skin. This helps to protect the skin from pathogenic infection.

The skin’s properties differ from one region of the body to another, as does the composition of the skin’s microbiota. The availability of nutrients and moisture partly dictates which microorganisms will thrive in a particular region of the skin. Relatively moist skin, such as that of the nares (nostrils) and underarms, has a much different microbiota than the dryer skin on the arms, legs, hands, and top of the feet. Some areas of the skin have higher densities of sebaceous glands. These sebum-rich areas, which include the back, the folds at the side of the nose, and the back of the neck, harbor distinct microbial communities that are less diverse than those found on other parts of the body.

Different types of bacteria dominate the dry, moist, and sebum-rich regions of the skin. The most abundant microbes typically found in the dry and sebaceous regions are Betaproteobacteria and Propionibacteria, respectively. In the moist regions, Corynebacterium and Staphylococcus are most commonly found. Viruses and fungi are also found on the skin, with Malassezia being the most common type of fungus found as part of the normal microbiota. The role and populations of viruses in the microbiota, known as viromes, are still not well understood, and there are limitations to the techniques used to identify them. However, Circoviridae, Papillomaviridae, and Polyomaviridae appear to be the most common residents in the healthy skin virome.

While the microbiota of the skin can play a protective role, it can also cause harm in certain cases. Often, an opportunistic pathogen residing in the skin microbiota of one individual may be transmitted to another individual more susceptible to an infection. For example, methicillin-resistant Staphylococcus aureus (MRSA) can often take up residence in the nares of health care workers and hospital patients; though harmless on intact, healthy skin, MRSA can cause infections if introduced into other parts of the body, as might occur during surgery or via a post-surgical incision or wound. This is one reason why clean surgical sites are so important.

Injury or damage to the skin can allow microbes to enter deeper tissues, where nutrients are more abundant and the environment is more conducive to bacterial growth. Wound infections are common after a puncture or laceration that damages the physical barrier of the skin. Microbes may infect structures in the dermis, such as hair follicles and glands, causing a localized infection, or they may reach the bloodstream, which can lead to a systemic infection.

In some cases, infectious microbes can cause a variety of rashes or lesions that differ in their physical characteristics. These rashes can be the result of inflammation reactions or direct responses to toxins produced by the microbes. Table 21.1 lists some of the medical terminology used to describe skin lesions and rashes based on their characteristics; Figure 21.4 and Figure 21.5 illustrate some of the various types of skin lesions. It is important to note that many different diseases can lead to skin conditions of very similar appearance; thus the terms used in the table are generally not exclusive to a particular type of infection or disease.

Table21.1

Figure 21.4 (a) Acne is a bacterial infection of the skin that manifests as a rash of inflamed hair follicles (folliculitis). The large whitehead near the center of the cheek is an infected hair follicle that has become purulent (or suppurative), leading to the formation of a furuncle. (b) An abscess is a pus-filled lesion. (credit b: modification of work by Bruce Blaus)

Figure 21.5 Numerous causes can lead to skin lesions of various types, some of which are very similar in appearance. (credit: modification of work by Bruce Blaus)

Although the eye and skin have distinct anatomy, they are both in direct contact with the external environment. An important component of the eye is the nasolacrimal drainage system, which serves as a conduit for the fluid of the eye, called tears. Tears flow from the external eye to the nasal cavity by the lacrimal apparatus, which is composed of the structures involved in tear production. The lacrimal gland, above the eye, secretes tears to keep the eye moist. There are two small openings, one on the inside edge of the upper eyelid and one on the inside edge of the lower eyelid, near the nose. Each of these openings is called a lacrimal punctum. Together, these lacrimal puncta collect tears from the eye that are then conveyed through lacrimal ducts to a reservoir for tears called the lacrimal sac, also known as the dacrocyst or tear sac.

From the sac, tear fluid flows via a nasolacrimal duct to the inner nose. Each nasolacrimal duct is located underneath the skin and passes through the bones of the face into the nose. Chemicals in tears, such as defensins, lactoferrin, and lysozyme, help to prevent colonization by pathogens. In addition, mucins facilitate removal of microbes from the surface of the eye.

The surfaces of the eyeball and inner eyelid are mucous membranes called conjunctiva. The normal conjunctival microbiota has not been well characterized, but does exist. One small study (part of the Ocular Microbiome project) found twelve genera that were consistently present in the conjunctiva. These microbes are thought to help defend the membranes against pathogens. However, it is still unclear which microbes may be transient and which may form a stable microbiota.

Use of contact lenses can cause changes in the normal microbiota of the conjunctiva by introducing another surface into the natural anatomy of the eye. Research is currently underway to better understand how contact lenses may impact the normal microbiota and contribute to eye disease.

The watery material inside of the eyeball is called the vitreous humor. Unlike the conjunctiva, it is protected from contact with the environment and is almost always sterile, with no normal microbiota.

The conjunctiva is a frequent site of infection of the eye; like other mucous membranes, it is also a common portal of entry for pathogens. Inflammation of the conjunctiva is called conjunctivitis, although it is commonly known as pinkeye because of the pink appearance in the eye. Infections of deeper structures, beneath the cornea, are less common. Conjunctivitis occurs in multiple forms. It may be acute or chronic. Acute purulent conjunctivitis is associated with pus formation, while acute hemorrhagic conjunctivitis is associated with bleeding in the conjunctiva. The term blepharitis refers to an inflammation of the eyelids, while keratitis refers to an inflammation of the cornea; keratoconjunctivitis is an inflammation of both the cornea and the conjunctiva, and dacryocystitis is an inflammation of the lacrimal sac that can often occur when a nasolacrimal duct is blocked.

Infections leading to conjunctivitis, blepharitis, keratoconjunctivitis, or dacryocystitis may be caused by bacteria or viruses, but allergens, pollutants, or chemicals can also irritate the eye and cause inflammation of various structures. Viral infection is a more likely cause of conjunctivitis in cases with symptoms such as fever and watery discharge that occurs with upper respiratory infection and itchy eyes. The table below summarizes some common forms of conjunctivitis and blepharitis.