Foundations of Microbiology PDF - Dr. Cyrus Taheri

Foundations of Microbiology (BIOL 2360) Dr. Cyrus Taheri Session 17 Microbial Interactions with Humans (Chapter 24) © 2015 Pears...

Foundations of Microbiology (BIOL 2360) Dr. Cyrus Taheri Session 17 Microbial Interactions with Humans (Chapter 24) © 2015 Pearson Education, Inc. Reading Assignment Watch the video found in the following link and answer the questions. https://www.youtube.com/watch?v=-nDPjGAGEak 1. How is fecal microbial transplantation (FMT) being used as a treatment for C. difficile infection? 2. FMT cures how many percent of treated people? 3. Stool sample from a healthy donor is screened to ensure that ……………………………………… © 2015 Pearson Education, Inc.  1. How is fecal microbial transplantation (FMT) being used as a treatment for C. difficile infection? Fecal matter can cause problems like an inflamed colon. The treatment FMT restores bad bacteria in the colon by replacing it with good bacteria from a donors stool. A common way of doing this (introducing bacteria into body) is with a colonoscopy. 2. FMT cures how many percent of treated people? 20 % to 60 % of patients 3. Stool sample from a healthy donor is screened to There are no Infectious diseases ensure that ……………………………………… © 2015 Pearson Education, Inc. Learning Outcome Define Microflora List where natural human microflora are present Outline the function of normal microflora Explain the component of skin microflora and define resident and transient skin microbes Explain the composition and functions of Gastrointestinal Tract Microflora Explain why GI microflora are important to human health and diseases like obesity and cancer Explain the microbial composition of the urogenital tract © 2015 Pearson Education, Inc. Learning Outcome Define disease, pathogen, pathogenicity, pathogenesis, and virulence Explain the sequence of events result in microbial pathogenesis Name different types of microbial toxins and explain their mode of action Explain how host’s conditions contribute to the outcome of microbial infection © 2015 Pearson Education, Inc. Microbes in and on human body Where in/ on our body they are present? Certain areas of the human body are a perfect environment for microbial growth and are occupied by a diverse community of microorganisms. Microorganisms that are normally associated with a human body are usually found in: Skin Oral cavity Gastrointestinal tract Respiratory tract Urogenital tract © 2015 Pearson Education, Inc. Figure 24.2 Overview of Major Microbial Populations in the Body Sites Sampled by Human Microbiome Projects Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Normal Human–Microbial Interactions Normal microflora is in a close association with human body. They have evolved together and developed a symbiotic relationship with us. Host and the microbial flora in and on host work in harmony and sometimes are collectively referred to as super-organism. A couple basic terminology: Microflora combined microbial communities that live a specific environment (e.g. human gastrointestinal microflora). Dysbiosis (Antonym of Eubiosis) is an alternation or imbalance of an individual's microflora relative to healthy state. © 2015 Pearson Education, Inc.  Normal Human–Microbial Interactions What they do? Microorganisms that are associated with a human body are divided into three groups: Do not harm but indirectly help A- Benign or neutral: They are the most common group. They indirectly help human health by preventing pathogens to grow (either directly by competition for space and resources or by producing certain antimicrobial compounds). For instance some component of normal skin microflora are shown to suppress MRSA growth on the skin. Exposure to certain neutral skin microbes is shown to boost immunity against Staphylococcus aureus. Less chance for pathogens causing problems-benefit to human health © 2015 Pearson Education, Inc.  Normal Human–Microbial Interactions B- Beneficial microbes: Some microbes produce certain types of nutrients (e.g. vitamins) that is used by the body. C- Opportunistic pathogens: Under favorable conditions such as compromised immune system or when normal microflora is damaged, they can cause diseases. For instance, Staphylococcus epidermidis which is a normal component of skin microflora can cause infection if it finds its way into the inner tissues. © 2015 Pearson Education, Inc. Microflora of the skin The skin is the most exposed organ in human body and makes a barrier around the body and responds appropriately to dangers including penetrating pathogens. However, despite a powerful immune system, many microbes manage to survive on the skin without triggering an immune response. It seems normal skin microflora is not only able to survive despite the immune system, it is able to communicate with it. Therefore, understanding the structure and function of skin microbiota has received lots of attentions in order to better understand skin health and new therapies for skin diseases. © 2015 Pearson Education, Inc. Microflora of the skin Human skin functions as an ecosystem that hosts a wide diversity of microorganisms including bacteria, fungi, protists, and viruses. In fact over 200 different genera of Mostly gram- bacteria and fungi including a positive Can survive few yeast species live on our better than gram skin. negative Bacteria are mostly gram- positive (Figure 23.2), because they are better able to survive in such a relatively dry and sometimes salty environment. © 2015 Pearson Education, Inc. Microflora of the skin Delivery mode affects baby’s skin microflora: Microbial colonization of the skin starts at birth and the type of microbes found on baby’s skin is primarily defined by the delivery mode: Babies born through the vaginal canal will be colonized by microbes present in the mother’s vagina. Babies born through a caesarian section will acquire a skin flora more similar to the mother’s skin. Encourage the baby for skin to skin contact ti get the microbes from the mothers skin © 2015 Pearson Education, Inc.  1- It is suggested that vaginal birth is optimal for ‘seeding’ a healthy microbiome for the baby and some studies suggest that microflora of babies born by vaginal birth are more diverse and contain more beneficial microbes. Can you propose an approach by which you could “seed” a more natural microflora for babies that are born via c-section? Would get a sterile swab and get the microbes from the mothers vagina (from fluids) to then put on the baby © 2015 Pearson Education, Inc. Microflora of the skin Microflora of the skin, a case study: In average 150 species of bacteria were identified on the palm of 51 volunteers. Only 17% similarity between the two hands of the same person was observed. The composition of microbes varied based on gender, time since last hand wash and dominant hand. Have a more similar composition of microorganisms Family members residing together showed more similarity in their microbial community than strangers. Pet owners showed a great similarity with the microbial communities existing on their pets. © 2015 Pearson Education, Inc. Microflora of the skin Microbes associated with skin are divided into two groups: Resident microbes: The ones that live on the skin for a long time and are considered a component of normal skin’s microflora Don’t change a lot Transient microflora: They are microbes that reach the skin through contacts with objects and skin to skin contact, but are usually unable to establish due to the competition of resident microbes or are removed by washing. Every time you touch something, you pick up microbes -Can come off with hand washing © 2015 Pearson Education, Inc. Microflora of the skin The composition and the diversity of skin microflora is primarily defined by the amount of moisture, weather, health condition, age, personal hygiene. Examples: Health condition: In HIV patients and people who their normal skin microflora is compromised, pathogenic fungi such as Candida can colonize the skin and cause serious infections. Age: While skin microflora is primarily gram-positive bacteria, young children carry more potentially pathogenic gram-negative bacteria. © 2015 Pearson Education, Inc. Microflora of the Gastrointestinal Tract The human gastrointestinal (GI) tract (i.e. the stomach, small intestine, and large intestine) hosts 1014 microbial cells (99% of human microflora). The stomach: It is highly acidic (pH 2) and therefore acts as a barrier and prevents microbes that get inside the body to enter into the GI. © 2015 Pearson Education, Inc. Microflora of the Gastrointestinal Tract Small intestine: Areas close to stomach are fairly acidic and its normal flora is similar to the stomach but as the pH increases the population of microbes increases. Large intestine: The density of microbes in this area is very high. © 2015 Pearson Education, Inc. Microflora of the Gastrointestinal Tract Products of intestinal microflora: Vitamins K and B12: Several important compounds such as vitamin k and vitamin B12 are produced by GI microflora. Our body does not synthesize these vitamins and vitamin B12 is not produced by plants. Also, certain types of steroids are produced by the liver, but first they are released to GI and GI microflora modifies them in a manner that it can be absorbed and used by the body. Some essential amino acids: Also, some essential amino acids are produced by GI microflora. For the GI microflora to change them © 2015 Pearson Education, Inc.  Microflora of the Gastrointestinal Tract Changes in GI microflora: A great portion of GI microflora (some 1013 cells) is removed from the body each day that need to be replaced (about 30% of feces dry mass). Is bacterium Different factors may affect gut microflora: Antibiotics Why fecal matter can cause diseases-because it contain Illness many bacterium Stress Diet Age © 2015 Pearson Education, Inc.  S17 – Q1 True of False? The negative impacts of antibiotics on human gut microflora is more when antibiotic is administrate orally? A- True B- False © 2015 Pearson Education, Inc.  Microflora of the Gastrointestinal Tract Examples: Oral consumption of antibiotic can drastically damage normal microflora of GI by: A. Killing normal microflora that usually results in diarrhea. B. Giving advantage to antibiotic resistant strains such as Staphylococcus aureus, Clostridium difficile, and Candida (yeast) that can cause infection and health complications. © 2015 Pearson Education, Inc.  Microbial Diversity of GI Microflora GI microflora is way more diverse than what we thought before and is critical to our health: Recent research using advanced molecular biology techniques has revealed that GI microflora is very important in early development of GI and overall health. Recent studies using molecular biology tools have identified between 3500 to 35,000 bacterial species living inside human gut. © 2015 Pearson Education, Inc.  Variation in GI microflora Variation in GI microflora: There is variation between GI microflora of different people, and can be affected by ethnicity and diet, but an individual’s GI microbial community is relatively stable during his/ her life. © 2015 Pearson Education, Inc.  GI Microflora and Human Health GI microflora can break down food further and extract GI microflora and obesity: more energy from food It is shown that in obese people the composition of GI microflora is different than non-obese individuals. It seems certain bacteria that are able to produce more fatty acids that are absorbed by the host are more abundant in obese people. GI microflora and pregnancy: Remarkably, it is shown that during the period between the first and third trimester of pregnancy microbial community of GI changes. These changes are associated with an increase in body fat. It seems women’s body manipulates its own microflora in preparation for a greater demand for fat in future. The mothers body changes the composition of GI tract bacteria to absorb more energy from food that she eats (to be able to optimize fat storage when carrying a child) © 2015 Pearson Education, Inc. GI Microflora and Human Health GI microflora and Cancer: It is suggested that change in the balance of human GI can be associated with certain types of cancer. It is also suggested that high fat and protein diets may alter GI microflora in a manner that more cancerogenic compound is produced by GI microflora while diets richer in carbohydrates may benefit the host. Animal based protein diet enhances the GI tract microbes that produce metabolites which create cancer They can change in a way where they don’t cause certain types of cancer © 2015 Pearson Education, Inc.  2- Imagine that the microbial communities of cancer patients and healthy people in a specific type of cancer are different. In cancer patients, the population of bacterium X is significantly more than healthy people. Can you claim that bacterium X is causing this type of cancer? You can not claim that x is causing cancer. Can say that there is correlation however. Correlation does not imply causation © 2015 Pearson Education, Inc. GI Microflora and Human Health GI microflora and potentials for new therapies: Understanding structure and function of normal human microflora can help us develop new therapies for certain diseases. This might include promoting the growth of beneficial microbes (e.g. through probiotics) and even through transplanting microbial communities from healthy to diseased individuals (e.g. Fecal microbiota transplant (FMT), or a stool transplant). Can get fecal microflora and give It to patients Known strategy used to treat certain diseases © 2015 Pearson Education, Inc.  Microflora of urogenital tract Microflora of urogenital tract (Figure 24.13) The bladder and the kidney in healthy people are sterile. However, a group of facultative aerobic bacteria usually colonize urethra both in healthy male and female individuals. Body should be free from microorganisms: if there are microbes there is a problem Figure 24.13 Microbial Growth in the Urogenital Tracts © 2015 Pearson Education, Inc.  Microflora of urogenital tract Urinary tract infections: Under certain conditions such as a change in pH opportunistic pathogens inhabiting urethra (such as Escherichia coli and Proteus mirabilis) can multiply and cause urinary tract infections. E. coli and P. mirabilis are common causes of urinary tract infections in women An adult female has a specific type of bacterium Microflora of the vagina: The vagina is usually colonized by a natural microflora but the composition of microbial communities inhabiting vagina changes at different stages of life: © 2015 Pearson Education, Inc.  Microflora of urogenital tract Microflora of the vagina in adult females: The vagina of the adult female is weakly acidic. This is because a member of vagina microflora in adult female, a bacterium called Lactobacillus acidophilus, continuously ferments free glycogen that exist in vagina and produces lactic acid (Figure 23.8b). The acidic condition in vagina is believed to reduce infections. Other microbes such as Candida, Streptococci, and E. coli also may be present in the vagina microflora. Able to absorb starch in vagina and metabolize it to produce lactic acid-makes it more acidic to prevent bacterial infections © 2015 Pearson Education, Inc.  Gram stain of Lactobacillus acidophilus predominant microbe in the vagina of adult women © 2015 Pearson Education, Inc. Figure 24.13 Figure b 23.8b  Microflora of urogenital tract Vaginal infection (vaginosis): Change in the balance of microflora or the introduction of exogenous pathogens can cause vaginal infection (vaginosis). Vaginosis can be caused by bacteria, fungi (yeast), or protists (i.e. protozoa). © 2015 Pearson Education, Inc.  Microflora of urogenital tract Microflora of vagina before puberty: Is natural L. acidophilus is rare, vagina does not produce glycogen and the pH is neutral. Normal microflora includes; streptococci, staphylococci, and E. coli. Microflora of vagina after menopause: Similar conditions to before puberty Glycogen production ceases, pH raises and microflora become similar to before puberty. © 2015 Pearson Education, Inc.  Microbial Pathogenesis Microbial pathogenesis: Is the process by which a pathogen causes disease in a host. Disease: Is the tissue damage or injury to the host caused by a pathogen or other factor, that impairs host function. Pathogen: A microorganism that grows in or on a host and causes disease. Pathogen benefits at the expense of the host. Pathogenicity: Process of disease transmission The ability of a pathogen to cause disease in the host. © 2015 Pearson Education, Inc. Bonus: Due next class (Find article and highlight area that answers question) 1) are there changes in skin microflora due to the hormonal changes throughout a female monthly cycle? https://pubmed.ncbi.nlm.nih.gov/10852812/ 2) PH of vagina in a female is acidic, does acidic PH enhance the rate fertility of the female? © 2015 Pearson Education, Inc.  Microbial Pathogenesis Virulence A measure of pathogenicity of the pathogen or the relative ability of a pathogen to cause disease. For instance, a highly virulent pathogen is a stronger pathogen than a weakly virulent pathogen. Terms virulence and pathogenicity sometimes are used interchangeably. Virulence is primarily defined by pathogen's genotype. For instance one strain of a pathogen could be highly virulent while another strain of the same species is not. © 2015 Pearson Education, Inc.  Pathogenicity and Virulence Measuring virulence Virulence can be estimated from experimental studies of the LD50 (lethal dose50). The number of pathogen cells that kills 50% of the host in a test group (Figure 23.10). Less number of a highly virulent pathogen is required to kill 50% of the target population. Highly virulent pathogens show little difference in the number of cells required to kill 100% of the population as compared to 50% of the population. © 2015 Pearson Education, Inc. Figure 25.9 Microbial Virulence Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Pathogenicity and Virulence; Attenuation The virulence of a microorganism can change over time. Attenuation is the decrease or loss of virulence especially when they are kept in laboratory condition for a long time. Can be used as vaccines as they don’t cause any diseases Sometimes, attenuated microbes can regain their virulence if they are inoculated to a host. © 2015 Pearson Education, Inc.  3- Why attenuation happens when virulent pathogens are grown on a synthetic culture medium? -Microbes loose their virulence when they are grown on a synthetic culture medium over time. -Strains that don’t have the genes become dominant (Natural selection) -When they don’t need the genes, they get rid of them © 2015 Pearson Education, Inc. Figure 25.1 Microbial Pathogenesis For a disease to happen: 1) Host must be exposed to pathogen 2) Pathogen should attach to cells (skin cells, epithelial etc.) 3) Microbe should able to get into cells 4) Be able to reproduce win cells and create a large population 5) Person becomes sick through multiplication Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Microbial Pathogenesis; Adherence Bacterial adherence can be facilitated by Extracellular structures such as slime layer, capsule, fimbriae, and pili (Figure 25.3). © 2015 Pearson Education, Inc. Figure 25.3b–c The Bacterial Capsule as a Facilitator of Pathogen Attachment Sticky capsule helps them attach to the host cell Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Figure 24.26 Colonization of Tooth Surfaces (a) colonization of a model tooth surface inserted into the mouth for only 6h. (b) The same surface under higher magnification. Note how slime layers hold bacterial cells together (arrow). Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Microbial Pathogenesis Invasion The ability of a pathogen to enter into a host cell or tissue. Multiplication *Host cell suffers as it’s losing iron The growth of a microorganism within the host, whether or not the host is harmed. The initial inoculum of a pathogen is insufficient to cause host damage, therefore pathogen needs to reproduce. Nutrients are a major limiting factor in microbial reproduction (growth) inside the host. A good example is Iron. Transferrins is a glycoprotein in the human body that carries Iron in the human body. To be able to retrieve iron for their reproduction, some bacteria produce siderophores that have a higher affinity for iron than Transferrins. This enables the pathogen to retrieve iron from the host cells. Pathogen should be bale to reproduce inside cell -Important factor: nutrients that are absorbed from host cell in order to grow © 2015 Pearson Education, Inc.  W22 Virulence Factors Pathogen is less virulent is it does’t cause disease Most pathogens produce virulence factors compounds that directly or indirectly promote their pathogenicity. Examples of virulence factor are enzymes such as protease and lipase that help pathogen to degrade host structures and helps the pathogen to spread through the body. If a bacterium can produce a toxin, it is more virulent © 2015 Pearson Education, Inc.  Virulence Factors Virulence factors are diverse: For instance, Salmonella species which are a group of human pathogens encode a large number of virulence factors (Figure 25.11) Toxins Siderophores Antibiotic resistance plasmids © 2015 Pearson Education, Inc. Figure 25.11 Virulence Factors in Salmonella Need to know names, and what they do -Virulence factor-can attach to host cell much easier Is toxic and can kill you Can move, and makes it harder for immune system to catch them Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Microbial Pathogenesis; Toxicity and Toxins Toxicity: is the ability of an organism to cause disease by means of a toxin that inhibits host cell function or kills host cells Toxins can travel to sites within the host that are not infected by the pathogen. Toxins are divided into two main groups: © 2015 Pearson Education, Inc.  Microbial Pathogenesis; Microbial Toxins Toxin produced inside the cell and is excreted outside the cell Exotoxins: Toxin (usually a protein) is released from the pathogen cell as it grows. Endotoxin: The lipopolysaccharide portion of the outer membrane of certain gram-negative bacteria, is released as bacterial toxin. Toxin produced outside the cell and is released inside the cell -Can only occur with gram-negative bacteria (due to membrane) © 2015 Pearson Education, Inc.  Exotoxins A specific type of exotoxins are AB toxins Consist of two subunits, A and B Work by binding to host cell receptor (B subunit) and transferring damaging agent (A subunit) across the cell membrane (Figure 25.13) Example: Botulinum toxin (Bacterium Clostridium botulinum produces a potent AB exotoxins (Botulinum toxin) that affect nervous tissue. One milligram of Botulinum toxin is enough to kill one million pigs). Powerful toxin © 2015 Pearson Education, Inc. Figure 25.13 The Activity of Diphtheria Toxin B=Binding -binds to protein at the membrane of host cell -Causes the toxicity Part A travels inside the cell cytoplasm -interferes with the translation step If cell can’t produce protein, then the cell is dead Copyright © 2021, 2018, 2015 Pearson Education, Inc. All Rights Reserved  Endotoxins Endotoxin Part of the outer membrane, is released into the environment The lipopolysaccharide portion of the cell envelope of certain gram-negative bacteria, which is a toxin when solubilized. Generally less toxic than exotoxins Cause a variety of physiological reactions such as fever or diarrhea. Figure 2.9 © 2015 Pearson Education, Inc. Cell wall structure in gram negative bacteria  Host Factors in Infection and Disease Host’s condition is a critical factor affecting the outcome of pathogen-host interaction (i.e. pathogenesis). Most important factors defining host’s susceptibility to diseases are: Age: infectious disease are more common in very young or very old individuals. Infants do not have a developed immune system and a normal microflora so they more susceptible to infectious diseases. Older people are also more susceptible to infectious diseases sometimes due to diminished immune responses. h © 2015 Pearson Education, Inc.  Host Factors in Infection and Disease Hormones are able to suppress the immune system and is cause for serious disease Stresses (e.g. fatigue, dehydration and etc.): Stresses can also increase susceptibility to infectious diseases. Rats subjected to intense physical activity showed a higher mortality rate due to bacterial infection. Hormones that are produced under stress inhibit immune responses may contribute to stress- related diseases. Poor diet (e.g. low protein and low calorie): Poor diet can also increase susceptibility to infections. Can multiply the result of death from an infectious disease -compromised hosts don’t have a strong immune system - © 2015 Pearson Education, Inc.  Host Factors in Infection and Disease Compromised host: Many hospital patients with non-infectious diseases are more susceptible to pathogens. For example during surgery pathogens may unintentionally be introduced into the body. Some patients are treated with immunosuppressive drugs that increase their susceptibility to infectious diseases. Infection with other pathogens also can increase susceptibility to other microbes (e.g. people who are suffering from AIDS are more susceptible to other microbial infection. © 2015 Pearson Education, Inc.  Host Factors in Infection and Disease Host Genetic: Host genetic is a key factor in susceptibility to infectious diseases. Some people are immune or significantly less susceptible to infectious diseases that are fatal to others (e.g. HIV, vCJD). Ex. Prion disease (mad cow disease) © 2015 Pearson Education, Inc.  Additional references The microbiome and cancer, Robert F. Schwabe and Christian Jobin, 2013 James A. Sanford and Richard L. Gallo (2013) Functions of the skin microbiota in health and disease James. Semin Immunol. 2013 November 30; 25(5): 370–377. © 2015 Pearson Education, Inc.