Microbiology and Biosafety Levels Quiz

Microbiology: Basic and Clinical Principles

• Chapter 10 covers Host-Microbe Interactions and Pathogenesis
• The chapter is presented by Janet Dowding, Ph.D., St. Petersburg College
• A clinical case, "The Case of the Deadly Mistake," is presented to explore how host-microbe interactions explain medical mysteries. Students should visit a specified study area in Mastering Microbiology to view the case.
• Students should be able to describe host-microbe interactions, discuss how shifts in normal microbiota levels or location may promote disease, explain why a commensal organism in one host could be a pathogen in another host, and explain tropism and its impact on pathogen emergence.
• Host-microbe interactions are dynamic give-and-takes. Normal microbiota colonize diverse body systems including skin, digestive, genital, urinary, and respiratory systems.
• Microbiota returns the favor by producing vitamins, competing with potential pathogens, and promoting immune system maturation. These microbes have mutualistic relationships with their hosts. Disrupting normal microbiota balance can compromise patient health.
• Pathogens are disease-causing microbes, exhibit adaptations to interact with host tissues, causing harm to the host.

Dysbiosis

• Dysbiosis is a disruption of microbiota.
• Examples include antibiotics killing normal microbiota in the gut, allowing Clostridioides difficile to flourish and cause disease.

Tropism

• Tropism is a pathogen's preference for specific host or tissue.
• Most microbes exhibit tropism, which may change over time.
• Emerging pathogens may broaden their host/tissue range to infect humans.
• Successful invasion doesn't guarantee disease. Host factors like age, gender, and overall health influence disease development.

Introduction to Virulence

• Pathogenicity is a microbe's ability to cause disease, whereas virulence describes the extent of disease a pathogen causes.
• Students should define virulence, various virulence factors (e.g., structures for adherence, invasion), host-microbe interactions that impact pathogen virulence and transmission, Ro and R values and their use in epidemic management, and attenuated pathogens.
• Virulence is an evolving property; making virulence factors requires energy investment, so only beneficial factors are maintained. Pathogens develop new factors in response to host and selective pressures.

Host Factors and Virulence

• Virulence factors damage host cells directly or provoke dangerous immune responses.
• Host properties such as immune fitness, and normal microbiota balance contribute to virulence. Examples demonstrating this include: influenza pandemics being more virulent in younger adults, and SARS-CoV-2 infections being more asymptomatic in children

Transmission and Virulence

• Virulence factors influence transmission. Understanding transmission helps deduce virulence factors.
• Pathogens easily transmitted to new hosts become more prevalent in populations.
• Basic reproduction number (R0) measures a pathogen's transmissibility, with R0 = 2.0 meaning one infected person infects an average of two others.
• R values change as host-pathogen interactions change in epidemics and pandemics, the effective reproduction number (Re) is more relevant

A Pathogen's Environment Influences Virulence

• Virulence is an evolving property; pathogens respond to differing selective pressures (host factors and environmental factors) causing changes to virulence factors. Attenuated pathogens are infectious but weakened, often developed from growth in cell cultures; they lack virulence factors but are still infectious, and usually do not cause disease in immunocompetent hosts.

The Dosage of Pathogen and Toxin Exposure Affects Host Health Outcomes

• Pathogens must first infect a host to establish disease.
• Infectious dose-50 (ID50) is the number of cells or virions needed to establish infection in 50% of exposed hosts. Less infectious pathogens have a higher ID50, while highly infectious pathogens have a lower ID50.
• Lethal dose-50 (LD50) is the amount of toxin needed to kill 50% of affected hosts that are not treated. ID50 and LD50 values can change based on species, immune fitness, and route of exposure.

Toxins

• Toxins are molecules that harm hosts, such as causing tissue damage or suppressing the immune response.
• Toxigenic microbes produce toxins, while toxemia involves toxins in the bloodstream, and there are two main classes of toxins: endotoxins and exotoxins.

Endotoxins

• Endotoxins are found in the outer membranes of Gram-negative bacteria. Released when Gram-negative bacteria die.
• Lipid A of LPS (lipopolysaccharide) is called endotoxin. It's toxic to humans and other animals. Excessive levels can trigger symptoms (fever, chills, body aches, hypotension, tachycardia, increased respiratory rate, and a feeling of disorientation, nausea, and vomiting) and potentially septic shock in humans. Septic shock, if left unchecked, is lethal as organs fail.
• Endotoxemia is endotoxin in the bloodstream, triggered by localized or systemic infections, introduction of Gram-negative microbiota to locations where not naturally found, and surgical complications.

Exotoxins

• Exotoxins are toxic proteins from actively growing bacteria, from both Gram-negative and Gram-positive bacteria.
• They differ in how they are named; they are named based on the organism producing them or the type of cells targeted (e.g., neurotoxins, enterotoxins, hepatotoxins, and nephrotoxins).
• Three main families exist based on their mode of action: Type I, Type II, and Type III exotoxins differ in their actions inside the host cell.

Five Steps to Infection

• Five general tasks for pathogens to establish an infection:
• Enter the host at a specific portal of entry
• Adhere to host tissues
• Invade host tissues to obtain nutrients.
• Replicate while warding off host defenses.
• Transmit to new host at specific portal of exit.
• Portals of entry and exit may be the same.

Skin, Ocular, Otic, and Parenteral Entry

• Integumentary system, based on its surface area, is our largest body system, and helps block most microbes from entering.
• Pathogens use various means (abrsisions, cuts, injections, surgical incisions, physically boring through skin to invade conjunctiva).

Respiratory tract entry

• Coughing and sneezing can spread pathogens in the air, from dust/soil. Infecting the respiratory tract doesn't guarantee an infection.

Gastrointestinal (GI) Tract Entry

• Frequently have fecal-oral transmission.
• Invade GI tract mucosa; infections originating in the GI tract can lead to GI tract symptoms.

Urogenital Tract and Transplacental Entry

• Sexually transmitted pathogens enter via vaginal or urethral mucosa. Additional pathogens can enter via skin of genitalia. Some pathogens exhibit vertical transmission via transplacental entry.

Adhesion Factors

• Adhesins are pathogen virulence factors for sticking to host cells. These may be particular to a cell (specific) or may not be (nonspecific). Examples include specific molecules like fimbriae or pili, and more general properties like hydrophobic interactions

Biofilms and Quorum Sensing

• Bacteria form biofilms on almost any natural or manmade surface; biofilms are a source for 60-80% of human infections. Many healthcare-associated infections originate from biofilms, as seen with implanted devices (like catheters, prosthetic joints), kidney deposits (stones), and gallbladder deposits (gallstones).
• Images illustrating biofilms on urinary catheters, and other examples.

Third: A Pathogen Must Invade Tissues and Obtain Nutrients

• After entering and adhering, pathogens have options of staying on the surface or invading deeper tissues, or even entering cells to be an intracellular pathogen.
• Invasion often damages host tissues and causes cytopathic effects

Invasins and Motility

• Invasion into host tissues is facilitated by both Invasins, which are used to breach host tissues, and motility, the ability of pathogens to move around in and between host cells and tissues. Examples include collagenases, neuraminidase, coagulases, lipases, and proteases, as well as flagella or motility.

Tools to Obtain Nutrients: Siderophores and Extracellular Enzymes

• Cellular pathogens need iron, so they use siderophores to snatch it from transferrin. Many pathogens secrete extracellular enzymes to break down local nutrients, helping them obtain nutrients as they damage host tissues. Examples include proteases and lipases.

Cytopathic Effects in the Host

• Pathogens often damage host cells in cytopathic effects. These are further classified into cytocidal (cell killing) and non-cytocidal (damaging but not killing) effects.

Fourth: A Pathogen Must Evade Host Immune Defenses So It Can Replicate

• Pathogens use various methods to evade the host immune systems. Such as hiding from immune defenses (intracellular pathogen lifestyle, latency, antigenic masking, mimicry and variation), and undermind them (interfering with phagocytosis, suppressing the immune response). Examples include interfering with phagocytosis by making a capsule, or neutralising digestive enzymes in phagocytes

Hiding From Host Immune Defenses

• Include intracellular pathways, latency, antigenic masking, antigenic mimicry, and antigenic variation

Undermining the Host Immune Response

• Pathogens can avoid immune detection while limiting/interfering with phagocytosis; they can use mechanisms to undermine/suppress immune response.

Fifth: A Pathogen Must Be Transmitted to a New Host

• The final step is transmission to a new host, which is facilitated by symptoms such as itching, sneezing, coughing, and diarrhea leading to portal of exit for the pathogens

Exiting the Host

• Portal of exit is the route a pathogen uses to exit the host.
• Examples include feces, urine, saliva, mucus, semen, blood or fluids drained from wounds.

Safety and Health Care:

• Criteria for assigning pathogens to biosafety levels (BSLs): Level of infectivity, Extent of disease caused and mortality rates, Mode of transmission, Availability of preventions and treatments

Biosafety Levels

• There are 4 major Biosafety levels to consider (from 1 to 4).
• BSL-1 agents are well-characterized, rarely cause disease, and pose minimal risk (e.g., Bacillus subtilis, E. coli K-12 strains).
• BSL-2 agents are infectious, not airborne, and include bodily fluids as potential transmission vectors (e.g., Staphylococcus aureus, Herpes simplex viruses, most influenza strains, Clostridium tetani, Salmonella species; HIV). BSL-2+ agents are more serious/incurable and not preventable.
• BSL-3 agents are serious or lethal, have airborne transmission, and may be treatable (e.g., Coxiella burnetii, Mycobacterium tuberculosis).
• BSL-4 agents are dangerous or exotic, lethal in humans, and lack cures or treatments (e.g., Ebola and Marburg).

Infection Control Practices

• Healthcare facilities have infection control teams to limit infection risks for workers and patients. Standard precautions treat all patients as potential sources of infection, using hand hygiene, glove changing, barrier clothing, face shields, mask-wearing, sharps waste management, and surface disinfection. Transmission precautions target specific infections using contact, droplet, and airborne precautions.

Test your knowledge on the benefits of normal microbiota, the implications of microbial imbalance, and the various biosafety levels. This quiz covers essential concepts such as pathogens, host interactions, and the role of microbiota in health. Perfect for microbiology students and professionals alike.