Entry into the Host

Portals of Microbe Entry

Microbes gain access to human tissues via mucosal surfaces within the body or epithelial surfaces on the outside of the body.

Learning Objectives

Recognize the various methods and types of microorganism transmission: vectors, hosts, horizontal, vertical transmissions

Key Takeaways

Key Points

  • Transmission can be direct (vertically or horizontally) or indirect.
  • Infectious agents are generally specialized for a particular method of transmission.
  • A locus is the point on the body where a pathogen enters.

Key Terms

  • infectious: Infectious diseases, also known as transmissible diseases or communicable diseases, comprise clinically evident illness (i.e., characteristic medical signs and/or symptoms of disease) resulting from the infection, presence, and growth of pathogenic biological agents in an individual host organism.
  • pathogen: Any organism or substance, especially a microorganism, capable of causing disease, such as bacteria, viruses, protozoa, or fungi. Microorganisms are not considered to be pathogenic until they have reached a population size that is large enough to cause disease.
  • contagious: Of a person, having a disease that can be transmitted to another person by touch.

Microbes gain access to human tissues via two main types of routes: mucosal surfaces within the body (linings of the respiratory, digestive, reproductive, or urinary tracts) or epithelial surfaces on the outside of the body (areas of skin that are either undamaged or compromised due to insect bites, cuts/scrapes, or other wounds).

Transmission of Microorganisms

Transmission of microorganisms occurs directly from one person to another by one or more of the following means:

  • droplet contact by coughing or sneezing on another person
  • direct physical contact by touching an infected person
  • direct physical contact (usually by touching soil contamination or a contaminated surface)
  • airborne transmission (if the microorganism can remain in the air for long periods)
  • fecal-oral transmission (usually from contaminated food or water sources)
  • contamination via intravenous drug us
  • contamination from blood given via transfusion or organ transplants

Transmission can also be indirect via another organism, either a vector (like a mosquito) or an intermediate host (like how a tapeworm from a pig can be transmitted to humans who ingest improperly cooked pork).

Horizontal or Vertical Transmission

Disease can also be directly transmitted in two ways: horizontally or vertically. Horizontal disease transmission occurs from one individual to another in the same generation (peers in the same age group), and can occur by either direct contact (licking, touching, biting), or indirect contact. Vertical disease transmission involves passing a disease causing agent vertically from parent to offspring.

Pathogens must have a way to be transmitted from one host to another to ensure their species ‘ survival. Infectious agents are generally specialized for a particular method of transmission. Taking an example from the respiratory route, from an evolutionary perspective a virus or bacteria that causes its host to develop coughing and sneezing symptoms has a great survival advantage: it is much more likely to be ejected from one host and carried to another.

A locus is the point on the body where a pathogen enters. In droplet contact and other airborne transmission it is generally the respiratory system through the nose, mouth, or eye surfaces. In direct physical and indirect contact it is generally through a wound in the skin or through a mucous membrane. In fecal-oral transmission, it is through the mouth. In vector-borne transmission, it is at the bite or sting of the vector. Other common indirect routes include contaminated food or water.

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Chest x-ray of a patient with tuberculosis.: In this chest X-ray of a person with advanced tuberculosis, the infections in both lungs are marked by white arrowheads and the formation of a cavity is marked by black arrows. The boundary between contagious and non-contagious infectious diseases is not perfectly drawn, as illustrated by tuberculosis, which is clearly transmissible from person to person, but was not classically considered a contagious disease.

Sexual Transmission

In sexual transmission, infection originates directly between surfaces in contact during intercourse (the usual route for bacterial infections and those infections causing sores) or from secretions (semen or the fluid secreted by the excited female). Sexually transmitted diseases such as HIV and Hepatitis B are thought to be transmitted through unprotected sexual intercourse (including anal and oral routes), contaminated blood transfusions, sharing hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Bodily fluids such as saliva and tears do not transmit HIV. Oral sexual practices have increased the incidence of herpes simplex virus 1 (which is usually responsible for oral infections) in genital infections and the increased incidence of the type 2 virus (more common genitally) in oral infections. Herpes diseases that are transmitted primarily by oral means may be caught through direct contact with an infectious area of the skin.

Direct Contact: Contagious Diseases

Diseases that can be transmitted by direct contact are called contagious (contagious is not the same as infectious). Although all contagious diseases are infectious, not all infectious diseases are contagious. Interestingly, some contagious diseases like tuberculosis were not classically considered to be contagious even though they are transmissible from person to person. Direct transmission can also occur by sharing a towel (where the towel is rubbed vigorously on both bodies) or items of clothing in close contact with the body (socks, for example) if they are not washed thoroughly between uses. Some diseases that are transmissible by direct contact include Athlete’s foot and impetigo.

Colonization and Growth

Infection begins when an organism successfully colonizes a host by entering the host’s body, growing and multiplying from there.

Learning Objectives

Distinguish between colonization and infection

Key Takeaways

Key Points

  • Some virulent bacteria produce special proteins that allow them to colonize parts of the host body.
  • Wound colonization refers to nonreplicating microorganisms within the wound, while in infected wounds replicating organisms exist and tissue is injured.
  • While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs.

Key Terms

  • infection: An uncontrolled growth of harmful microorganisms in a host.

Infection begins when an organism successfully colonizes by entering the body, growing and multiplying from there. Most humans are not easily infected. Those who are weak, sick, malnourished, have cancer or are diabetic possess an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections.

Entrance to the host generally occurs through the mucosa in orifices like the oral cavity, nose, eyes, genitalia, anus, or open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids. Some virulent bacteria produce special proteins that allow them to colonize parts of the host body. Helicobacter pylori is able to survive in the acidic environment of the human stomach by producing the enzyme urease. Colonization of the stomach lining by this bacterium can lead to gastric ulcer and cancer. The virulence of various strains of Helicobacter pylori tends to correlate with the level of production of urease.

Wound colonization refers to nonreplicating microorganisms within the wound, while in infected wounds replicating organisms exist and tissue is injured. All multicellular organisms are colonized to some degree by extrinsic organisms and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon, and an example of the latter is various species of staphylococcus that exist on human skin. Neither of these colonizations are considered infections.

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Staphylococcus aureus: Staphylococcus is a Gram-positive bacteria which includes several species that can cause a wide variety of infections in humans and other animals through infection or the production of toxins.

The difference between an infection and a colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and viridans streptococci, prevent the adhesion and colonization of pathogenic bacteria. They thus have a symbiotic relationship with the host, preventing infection and speeding wound healing.

The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include: the route of entry of the pathogen and the access to host regions that it gains, the intrinsic virulence of the particular organism, the quantity or load of the initial inoculant, and the immune status of the host being colonized. As an example, the Staphylococcus species remains harmless on the skin. But when present in a normally sterile space, such as in the capsule of a joint or the peritoneum the Staphylococcus species multiplies without resistance and creates a burden on the host.

Pathogenicity Islands and Virulence Factors

Pathogenicity islands (PAIs) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer.

Learning Objectives

Describe the traits characterizing a pathogenicity island and its advantages

Key Takeaways

Key Points

  • Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or tRNA genes, which act as sites for recombination into the DNA.
  • PAIs are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species.
  • PAIs carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins.

Key Terms

  • pathogenicity island: A distinct class of genomic islands acquired by microorganisms through horizontal gene transfer.
  • virulence factor: Molecules expressed and secreted by pathogens (bacteria, viruses, fungi and protozoa) that enable them to achieve colonization of a niche in the host, immunoevasion, immunosuppression, entry into and out of the cells, and obtaining nutrition from the host.

Pathogenicity Islands and Virulence Factors

Pathogenicity islands (PAIs) are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms, but are usually absent from those nonpathogenic organisms of the same or closely related species. These mobile genetic elements may range from 10-200 kb, and may encode genes contributing to the virulence of the respective pathogen. Typical examples are adherence factors, toxins, iron uptake systems, invasion factors and secretion systems.

Pathogenicity islands are discrete genetic units flanked by direct repeats, insertion sequences or tRNA genes, which act as sites for recombination into the DNA. Cryptic mobility genes may also be present, indicating the provenance as transduction.

One species of bacteria may have more than one PAI (i.e. salmonella has at least five). PAIs are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon. PAIs carry genes encoding one or more virulence factors, including, but not limited to, adhesins, toxins, or invasins. They may be located on a bacterial chromosome or may be transferred within a plasmid. The GC-content of pathogenicity islands often differs from that of the rest of the genome, potentially aiding in their detection within a given DNA sequence.

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Trimeric Autotransporter Adhesin structure: The structure on the top (outside) of the outer membrane is a TAA protein. Various parts of the TAA are labelled, including the N-terminal head, stalk domain and C-terminal membrane anchor.

PAIs are flanked by direct repeats; the sequence of bases at two ends of the inserted sequence are the same. They carry functional genes such as integrases, transposases, or part of insertion sequences, to enable insertion into host DNA. PAIs are often associated with tRNA genes, which target sites for this integration event. They can be transferred as a single unit to new bacterial cells, thus conferring virulence to formerly benign strains.

Adherence

Adhesins are cell-surface components or appendages of bacteria that facilitate bacterial adhesion to other cells or to inanimate surfaces.

Learning Objectives

Review the role of adhesins, including fimbriae and the Dr family, in pathogenic bacteria

Key Takeaways

Key Points

  • Adhesins are a type of virulence factor.
  • Adherence is an essential step in bacterial pathogenesis or infection, required for colonizing a new host.
  • Fimbriae are believed to be involved in attachment to solid surfaces or to other cells and are essential for the virulence of some bacterial pathogens.

Key Terms

  • adhesin: Any of several factors that enable bacteria to adhere to epithelial surfaces as a step towards infection.
  • fimbriae: Fine filaments of protein distributed over the surface of bacteria that are believed to be involved in attachment to solid surfaces or to other cells, and are essential for the virulence of some bacterial pathogens.

Adhesins are cell-surface components or appendages of bacteria that facilitate bacterial adhesion or adherence to other cells or to inanimate surfaces. Adhesins are a type of virulence factor. Adherence is an essential step in bacterial pathogenesis or infection, required for colonizing a new host. For example, nontypeable Haemophilus influenzae expresses the adhesins Hia, Hap, Oap, and a hemagglutinating pili.

Fimbriae are fine filaments of protein, just 3–10 nanometers in diameter and up to several micrometers in length. They are distributed over the surface of the cell, and resemble fine hairs when seen under the electron microscope. Fimbriae are believed to be involved in attachment to solid surfaces or to other cells, and are essential for the virulence of some bacterial pathogens. Most fimbriae of Gram-negative bacteria function as adhesins, but in many cases the actual adhesin is a minor subunit protein at the tip of the fimbriae. In Gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. To effectively achieve adherence to host surfaces, many bacteria produce multiple adherence factors called adhesins.

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E. coli fimbriae: In bacteriology, a fimbria (plural fimbriae; abbreviated FIM) is an appendage composed of curlin proteins that can be found on many Gram-negative and some Gram-positive bacteria that is thinner and shorter than a flagellum. This appendage ranges from 3-10 nanometers in diameter and can be up to several micrometers long.

The Dr family of adhesins bind to the Dr blood group antigen component of decay-accelerating factor (DAF). These proteins contain both fimbriated and afimbriated adherence structures and mediate adherence of uropathogenic Escherichia coli to the urinary tract. They do so by inducing the development of long cellular extensions that wrap around the bacteria. They also confer the mannose-resistant hemagglutination phenotype, which can be inhibited by chloramphenicol. The N-terminal portion of the mature protein is thought to be responsible for chloramphenicol sensitivity. Also, they induce activation of several signal transduction cascades, including activation of PI-3 kinase. The Dr family of adhesins are particularly associated with cystitis and pregnancy-associated pyelonephritis.

Adhesins are attractive vaccine candidates because they are often essential to infection and are surface-located, making them readily accessible to antibodies. The effectiveness of anti-adhesin antibodies is illustrated by studies with FimH, the adhesin of uropathogenic Escherichia coli (UPEC). In animal models, passive immunization with anti FimH-antibodies and vaccination with the protein significantly reduced colonization by UPEC. Moreover, the Bordetella pertussis adhesins FHA and pertactin are components of 3 of the 4 acellular pertussis vaccines currently licensed for use in the U.S.

Host Risk Factors

Individuals who are weak, sick, malnourished, have cancer, or are diabetic have increased susceptibility to chronic or persistent infections.

Learning Objectives

Recognize the risk factors that increase chance of disease

Key Takeaways

Key Points

  • Risk of infection is a nursing diagnosis; “the state in which an individual is at risk to be invaded by an opportunistic or pathogenic agent (virus, fungus, bacteria, protozoa, or other parasite) from endogenous or exogenous sources” is the diagnostic definition of risk.
  • Examples of risk factors includes decreased immune system secondary to disease, compromised circulation secondary to peripheral vascular disease, compromised skin integrity secondary to surgery, or repeated contact with contagious agents.
  • Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed from the surgeon to the patient or vice versa.

Key Terms

  • opportunistic infection: Any infection that causes disease and occurs only when the host’s immune system is impaired.
  • colitis: inflammation of the colon.
  • vaccination: inoculation with a vaccine in order to protect a particular disease or strain of disease.

Most humans are not easily infected. Those who are weak, sick, malnourished, have cancer, or are diabetic have increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system or who are on immunosuppressive drugs are particularly susceptible to opportunistic infections.

Risk of infection is a nursing diagnosis which is defined as “the state in which an individual is at risk to be invaded by an opportunistic or pathogenic agent (virus, fungus, bacteria, protozoa, or other parasite) from endogenous or exogenous sources. ” The risk of infection depends on a number of endogenous sources. Skin damage from incision can increase a patient’s risk of infection, as can very young or old age, due to a naive or compromised immune system respectively. Examples of risk factors include decreased immune system resulting from disease, compromised circulation caused by peripheral vascular disease, compromised skin integrity as a result of surgery, or repeated contact with contagious agents.

Risk Reduction

Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed between the surgeon and the patient. Frequent hand washing remains the most important defense against the spread of unwanted organisms. Good nutrition is necessary to reduce risk. So is a healthy lifestyle. By avoiding illicit drugs, using a condom, and entering an exercise program one can improve one’s risk factors. Foods should be cooked to recommended temperatures; avoid foods that have been left outside for long. One should not take antibiotics for longer than needed or when they are not needed—long term use of antibiotics leads to resistance and increased the chance of developing opportunistic infections like clostridium difficile colitis. Vaccination is another vital means of preventing infections by encouraging the development of immune resistance in vaccinated hosts.

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How C. difficile spreads: C. difficile is transmitted from person to person by the fecal-oral route. The organism forms large numbers of heat-resistant spores. These are not killed by alcohol-based hand cleansers or routine cleaning of surfaces. These spores remain viable in the hospital or nursing home environment for long periods of time. Because of this, the bacteria can be cultured from almost any surface in the hospital. Once spores are ingested by a patient, they pass through the stomach unscathed because of their acid-resistance. They germinate into vegetative cells in the colon upon exposure to bile acids, and multiply.

Innate Resistance

Several barriers protect organisms from infection including mechanical, chemical, and biological barriers.

Learning Objectives

Discuss the various innate barriers within humans that provide protection from infection

Key Takeaways

Key Points

  • The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.
  • The human microbiome (or human microbiota ) is the aggregate of microorganisms that reside on the surface and in deep layers of skin, in the saliva and oral mucosa, in the conjunctiva, and in the gastrointestinal tracts.
  • Some of these organisms perform tasks that are useful for the human host, but the majority have no known beneficial or harmful effect.

Key Terms

  • lysozyme: A bacteriolytic (or antibiotic) enzyme found in many animal secretions and in egg white.
  • microbiota: The microbial flora harbored by normal, healthy individuals.
  • flora: the microorganisms that inhabit some part of the body, such as intestinal flora

Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. However, as organisms cannot be completely sealed against their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.

Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins. Enzymes such as lysozyme and phospholipase A2 in saliva, tears, and breast milk are also antibacterials. Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens. Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron. This reduces the probability that pathogens will reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an “overgrowth” of fungi and cause conditions such as a vaginal candidiasis (a yeast infection). There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in unpasteurized yogurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis and inflammatory bowel diseases. Inflammation is one of the first responses of the immune system to infection.

The human microbiome (or human microbiota) is the aggregate of microorganisms that reside on the surface and in deep layers of skin, in the saliva and oral mucosa, in the conjunctiva, and in the gastrointestinal tracts. They include bacteria, fungi, and archaea. Some of these organisms perform tasks that are useful for the human host. However, the majority have no known beneficial or harmful effect. Those that are expected to be present, and that under normal circumstances do not cause disease, but instead participate in maintaining health, are deemed members of the normal flora.

Populations of microbes (such as bacteria and yeasts) inhabit the skin and mucosa. Their role forms part of normal, healthy human physiology. However, if microbe numbers grow beyond their typical ranges (often due to a compromised immune system) or if microbes populate atypical areas of the body (such as through poor hygiene or injury), disease can result.

Many of the bacteria in the digestive tract are collectively referred to as the gut flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora, the word microbiome is also in use. They are able to break down certain nutrients such as carbohydrates that humans otherwise could not digest. The majority of these commensal bacteria are anaerobes, meaning they survive in an environment with no oxygen. Normal flora bacteria can act as opportunistic pathogens at times of lowered immunity.

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Gut Flora: Gut flora consists of microorganisms such as Escherichia Coli that live in the digestive tracts of animals. It is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora. The word microbiome is also in use.

Archaea are present in the human gut, but, in contrast to the enormous variety of bacteria in this organ, the numbers of archaeal species are much more limited. Fungi, in particular yeasts, are present in the human gut. The best-studied of these are Candida species. This is because of their ability to become pathogenic in immune compromised hosts. Yeasts are also present on the skin, particularly Malassezia species, where they consume oils secreted from the sebaceous glands.

A small number of bacteria are normally present in the conjunctiva. Staphylococcus epidermidis and certain coryneforms such as Propionibacterium acnes are dominant. The lachrymal glands continuously secrete, keeping the conjunctiva moist, while intermittent blinking lubricates the conjunctiva and washes away foreign material. Tears contain bactericides such as lysozyme, so that microorganisms have difficulty in surviving the lysozyme and settling on the epithelial surfaces.

The gut flora is the human flora of microorganisms that normally live in the digestive tract and can perform a number of useful functions for their hosts. Though people can survive with no gut flora, the microorganisms perform a host of useful functions such as fermenting unused energy substrates, training the immune system, preventing growth of harmful species, regulating the development of the gut, producing vitamins for the host (such as biotin and vitamin K), and producing hormones to direct the host to store fats. However, in certain conditions, some species are thought to be capable of causing disease by causing infection or increasing cancer risk for the host.