A Primer on Microbiology

Introduction to Microorganisms That Interact with Humans

In this section, we will introduce the main categories of organisms that interact with humans both as part of the human microbiome and those that are able to cause disease. Some organisms are primarily colonizers of humans and exist in a symbiotic relationship, others are primarily pathogens that cause disease, and some are able to do both. The predominant categories of organisms that interact with humans are bacteria, viruses, fungi, protozoa, and helminths. See Table 3.1 for key features of these groups. Prions, algae, and ectoparasites are able to cause human disease as well, but are much less common. We will discuss the basic microbiology and touch on elements of the microbiome niche, epidemiology, clinical presentation, and management, though these latter elements will be discussed in greater detail in the following chapters.

Table 3.1

Key Features of Groups of Organisms That Interact with Humans

	Size (μM)	Nucleic Acid	Cell Type	Motile	Method of Replication
Virus	0.002–0.2	DNA or RNA	Noncellular	None	Nonbinary fission
Bacteria	1–5	DNA and RNA	Prokaryotic	Some	Binary fission
Fungi	3–10	DNA and RNA	Eukaryotic	None	Budding/mitosis
Protozoa	15–25	DNA and RNA	Eukaryotic	Most	Mitosis
Helminth	Can be macroscopic	DNA and RNA	Eukaryotic	Most	Mitosis

DNA, Deoxyribonucleic acid; RNA, ribonucleic acid.

Bacteria

Bacteria are small, single-celled, prokaryotic organisms that grow in differing environments with varying levels of oxygen. Those that require oxygen are considered aerobic. Those that require oxygen but at less than atmospheric levels are microaerophilic, and those that do not require oxygen are anaerobic. Anaerobic bacteria can be either facultative anaerobes (adapt to and survive in aerobic conditions) or strict anaerobes (cannot survive in the presence of high levels of oxygen). Bacteria are typically identified according to their staining properties. The Gram stain separates bacteria based on their cell wall structure in that Gram-positive organisms retain the violet color due to their thick peptidoglycan cell wall and Gram-negative organisms cannot retain the violet color after decolorization, as their peptidoglycan is much thinner. They are counterstained with safranin and appear pink instead ( Fig. 3.1 ). Thus begins the separation of Gram-positive and Gram-negative organisms: purple and pink. Once the bacteria are stained, they can be further characterized by their shape and configurations as cocci (spheres), bacilli (rods), filamentous, beaded, and pleomorphic.

Fig. 3.1, Gram-stained smear of urethral exudates showing intracellular Gram-negative diplococci that are characteristic of gonorrhea.

Gram-Positive Bacteria

Staphylococci

Staphylococci are Gram-positive cocci that form clusters ( Fig. 3.2 ). They are a component of the skin microbiome and are opportunistic pathogens, in that they cause disease if given the right environment or opportunity. Staphylococcus aureus is the most frequent cause of staphylococcal sepsis. Infection results in severe disease in humans due to its ability to produce numerous virulence factors ranging from those causing tissue damage and disease spread to toxic shock from superantigens. Given its niche, S. aureus is one of the leading causes of skin and soft tissue infections. However, because of its ability to spread, S. aureus is also a common cause of bacteremia, endocarditis, and abscesses throughout the body ( Table 3.2 ).

Table 3.2

Common Species of Staphylococci Causing Human Disease

	Epidemiology	Clinical Disease
S. aureus	Colonizes nares and skin	Skin and soft tissue infections Bacteremia Endocarditis Epidural abscess
S. epidermidis	Normal flora of skin	Infection of prosthetic materials Catheter-associated bloodstream infections
S. saprophyticus	Colonizes genitourinary tract	Urinary tract infections

Streptococci

Streptococci are Gram-positive cocci that tend to form chains rather than clusters in culture ( Fig. 3.3 ). Once a streptococcus is identified, further speciation is warranted, given the large number of streptococci and various virulence capabilities. Traditionally, laboratories have separated streptococci via two different but useful ways: hemolysis patterns and Lancefield antigen testing. When growing on a blood agar plate, streptococci can cause three different hemolysis patterns: beta (full hemolysis), alpha (partial hemolysis), and gamma (no hemolysis) ( Fig. 3.4 ). Beta-hemolytic species tend to cause fairly destructive clinical presentations, given their ability to destroy tissue, as evidenced by the hemolysis. However, alpha- and gamma-hemolytic species can cause human disease as well, and depending on the host factors, quite dramatically at times.

Fig. 3.4, Examples of various types of hemolysis on blood agar. (A) Streptococcus pneumoniae showing alpha-hemolysis (i.e., greening around colony). (B) Staphylococcus aureus showing beta-hemolysis (i.e., clearing around colony). (C) Enterococcus faecalis showing gamma-hemolysis (i.e., no hemolysis around colony).

Along with hemolysis patterns, Lancefield antigens are used to name specific streptococci. Streptococcus pyogenes contains the “A” Lancefield antigen, and thus is also called group A streptococci (GAS). GAS are beta-hemolytic and well known as the agent that causes streptococcal pharyngitis. It can also cause severe skin and soft tissue infections (cellulitis and necrotizing fasciitis, respectively). The human immune response to GAS antigens can also be associated with disease, most commonly rheumatic fever and post-streptococcal glomerulonephritis. Group B streptococci (GBS) correspond to the Streptococcus agalactiae species, whose niche is the gastrointestinal (GI) and genitourinary tracts. Given this location, it is responsible for neonatal sepsis and infections. Mothers who test positive for GBS are treated with penicillin before delivery to prevent disease in the newborns.

Alpha-hemolytic streptococci known to cause disease include Streptococcus pneumoniae, which is typically found in the nasopharyngeal niche, and viridans group streptococci, typically found in the oropharyngeal niche. S. pneumoniae is a well-known cause of otitis media, lower respiratory tract infections, and disseminated infections such as meningitis and bacteremia. Patients without functioning spleens are at increased risk, given their inability to effectively clear this encapsulated organism ( Table 3.3 ).

Table 3.3

Streptococci

	Epidemiology	Clinical Disease
S. pyogenes (group A beta-hemolytic streptococci)	Colonizes skin	Cellulitis Necrotizing fasciitis Pharyngitis Rheumatic fever Post-streptococcal glomerulonephritis
S. agalactiae (group B beta-hemolytic streptococci)	Colonizes gastrointestinal and genitourinary tracts	Neonatal sepsis Peripartum infections Cellulitis
S. pneumoniae	Can colonize nasopharynx	Pneumonia Meningitis Otitis media Sinusitis
Viridans group Streptococci (e.g., S. mutans )	Normal flora of mouth and gastrointestinal tract	Caries Endocarditis
Enterococci	Gastrointestinal tract	Intraabdominal infections Bacteremia Central-line infections Endocarditis

Enterococci are also Gram-positive cocci that form chains. It is worth noting that though they are in a separate genus from streptococci, they do have a Lancefield carbohydrate antigen (group D). This was the reason why previously, enterococci used to be included in the Streptococcus genus as group D streptococci. However, further identification methods led to the creation of a separate genus. The Enterococci niche is the GI tract, with a special predilection for the biliary tract. Thus these organisms can cause cholangitis, but are also known for bacteremia and subacute endocarditis.

Though most Gram-positive disease is caused by cocci, Gram-positive rods are components of the human microbiome and pathogens. Important elements of the human microbiome include Cutibacterium (formerly Propionibacterium ) acnes on the skin, Actinomyces species in the mouth, and Lactobacillus species in the vagina. Gram-positive rods are more often associated with disease. Listeria monocytogenes can cause food-borne illnesses ranging from mild, in immunocompetent hosts, to severe disseminated disease, such as bacteremia and meningitis, in pregnant and immunocompromised hosts. Some toxin-producing Gram-positive organisms include Clostridium botulinum, the cause of botulism ; C. tetani, the cause of tetanus ; C. perfringens, the cause of food-borne illness and gas gangrene; and C. difficile, causing antibiotic-associated colitis. Corynebacterium diphtheriae causes diphtheria, and Bacillus anthracis causes anthrax.

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