Interactions Between Microbes and Humans PDF

Interactions Between Microbes and Humans Chapter 11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Learning Outcomes: Section 11.1 1. Enumerate the sites where normal microbiota is found in humans. 2. Discuss the modes of tran...

Interactions Between Microbes and Humans Chapter 11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Learning Outcomes: Section 11.1 1. Enumerate the sites where normal microbiota is found in humans. 2. Discuss the modes of transfer of microbiota to a neonate 3. Examine the role of microbial antagonism The Human Host The human body in a state of dynamic equilibrium with microorganisms -healthy individuals have a peaceful coexistence with microbes and a lack of disease (Eubiosis) -occasionally the balance tips in favor of microbes and disease Resident Normal Biota : The Human as a Habitat also known as indigenous flora or normal flora Ratio of bacteria to human cells (adult body) –1:1 (approx.) Microbiome (total microbiota genes): 150-fold greater than human genome include an array of Bacteria  Human Microbiome Project Based on Metagenomics Compare known microbial DNA sequences with those present in human body parts Determines what role the normal biota play in human health and disease Bacterial makeup for a given site on a body varies from person to person not only in type, but also in abundance Skin and vaginal sites showed smaller diversity than the mouth and gut, showing the greatest richness  The human body has an endless variety of microbial niches Most areas of the body in contact with the outside environment harbor resident microorganisms Internal organs and tissue and their fluids are microbe-free Normal flora have a complex relationship with the human host, not being harmful to the host Anatomical Sites/Fluids Thought to Be Sterile  Concept Check-1 Microbiome is the study of ______genomes to identify ______flora of an individual. A. Human; bacterial B. Microbial; indigenous C. Bacterial; viral D. Fungal; bacterial Initial Colonization of the Newborn Uterus and its contents are normally sterile during embryonic and fetal development Breaking of fetal membranes first exposes the infant to microbes -premature rupturing of membranes exposes the infant to infection -antibiotics are sometimes given to mothers who do not deliver within 24 Initial Colonization (cont’d) Comprehensive exposure occurs during the birth process itself -baby becomes colonized with the mother’s vaginal biota -babies born by caesarean section are colonized by adult skin biota -within 8 – 12 hours after delivery, a vaginally delivered baby has been colonized by streptococci, staphylococci, and lactobacilli Initial Colonization (cont’d)… Colonization of the large intestine -bottle fed infants: mixed population of coliforms, lactobacilli, enteric streptococci, staphylococci -breast-fed infants: Bifidobacterium whose growth is favored by a growth factor in milk; metabolizes sugars into acids to protect the infant from intestinal pathogens Colonization continues as the infant comes into contact with family members, health care personnel, the environment, and food The Origins of Microbiota in Newborns  Concept Check-2 Which of the following body sites is generally not colonized by known normal biota? A. skin and mucous membranes B. external genitalia C. gastrointestinal tract D. kidneys and bladder E. respiratory tract Does the paradigm of sterile womb need a shift? Microbiota & Neonate development  The development of the human gut microbiome begins before birth and proceeds in a systematic manner  Affected by factors including maternal oral microbiome, mode of delivery, maternal and infant diet, environmental exposures.  Microbiome development occurs simultaneously with, and plays a key role in the neurologic system maturation  Concept Check-3 A vaginally delivered baby is colonized with _______________within 8-12 hours of delivery. A. Streptococci B. Staphylococci C. Lactobacilli D. All E. None  Role of Microbiota Microbial antagonism -normal biota are unlikely to be displaced by incoming microbes (pathogens) -Spares limited number of attachment sites -chemical or physiological environment created by resident biota is hostile to other microbes Microbiome converts indigestible food particles into Gut-Microbiome-Brain Axis Case study 1: Bacteroidetes fragilis (B- frag) The classical view of the&immune Humansystem Immune is full System of military metaphors & antagonistic lingo How intelligent is this system? Does it recognize the foe on its own?? B-frag (obligate anaerobe) is part of the normal microbiota of the human colon Mezmanian group: B-frag can prevent and cure inflammatory diseases like colitis & multiple sclerosis in germ-free mice They went further to connect Polysaccharide A (present in B-frag cell wall) with anti- inflammatory effects in the remission/prevention Another part of B-frag Neuroscientist Paul Patterson: infected pregnant mice with viral component that triggered immune responses in moms Newly-born babies develop symptoms similar to 2 human conditions: Autism & Schizophrenia What is the common link? Human background: Association studies indicate pregnant women who suffered with flu or measles – more likely to have autistic & schizophrenic babies Both in human & mice cases of autism: GI tract disorders common- both had unusual gut microbiota  Case Study 2:Breast Milk & Bifidobacterium infantis  B. infantis is a friendly oral/gut microbiota, dominant in the stools of breast-fed infants  Milk is a mammalian innovation. It contains 200 HMO (human milk oligosaccharides)- cannot be used by babies  What is the evolutionary significance?  HMOs pass on to the large intestine where they meet the hosts: B. infantis  B. infantis breaks them down into short- chain fatty acids that feed on infant’s gut cells – stimulates gut cells to make  B. infantis further makes babies brainier by adding to the supply of sialic acid while digesting HMOs  Seems human milk has evolved to nourish this microbe as it nourishes the next gen  Case Study 3: Yoghurt, probiotics, prebiotics, psychobiotics  Bifidobacterium (specific strain) reduced depression in people suffering with irritable bowel syndrome (IBD) in a human clinical trial  Likewise, two servings of microbe-rich yoghurt produced less activity in parts of the brain involved in processing emotions in women  Lactobacillus rhamnosus reduced anxiety and timidity in germ-free mice through modulating GABA (a neurotransmitter) levels in the brain  GABA is implicated in human cases of “Leaky Gut” An individual’s immune systems depend greatly on the gut microbiome’s function of epithelial cell renewal and management of intestinal integrity Without a healthy intestinal wall, bacteria migrate across the gut into general circulation increasing systemic inflammation. “Leaky gut” also speeds up the migration of pathogens Increased intestinal permeability is the possible mechanism of dysbiosis and low grade inflammatory disorders like obesity,  Concept Check-4 Dysbiosis refers to a A. Condition of diarrhea B. Balanced microbiota & health C. Prenatal imbalance D. Imbalanced microbiota & disease  Concept Check-5 Which of the following gut indigenous flora show connection to the brain functions A. Streptococci B. B-frag C. Lactobacilli D. B. infantis E. b, c, d  Concept Check-6 In the above case studies, importance of B- frag has been demonstrated by their roles in alleviating A. Inflammatory conditions B. Multiple sclerosis C. Autism, Schizophrenia D. all  Concept Check-7 In the above case studies: the baby’s gut flora _______ has been demonstrated to be nourished by mom’s breast milk A. B-frag B. B. infantis C. Lactobacillus rhamnosus D. b E. all  Factors affecting Gut Dietmicrobiome & Genetics Low fat/protein food, unsaturated fatty acids, whole grains, certain probiotics  healthy gut microbiome, enhance intestinal integrity and reduce excessive systemic inflammation Short chain fatty acids (SCFA) e.g., acetate, propionate and butyrate are the by products of fiber fermentation (prebiotics)- serve as an energy source to intestinal epithelial cells SCFA by the gut microbiota is negatively correlated with body mass index Studies on omega-3 (PUFAs) also suggest protection of the intestinal wall Ratio of Bacteroidetes & Firmicutes  Pregnancy & Microbiome Hormonal changes in pregnancy & Microbiome  Estrogen & progesterone Metabolic Changes in pregnancy & Microbiome Lipid metabolism correlates with the changes in microbiome (Firmicutes/Bacteroidetes) Old Age & Microbiome  Obesity & Microbiome:  A recent study on the wait gain in pregnant obese women found an association between low abundance of butyrate- producing bacteria & blood pressure  Excess wait gain and a dysbiotic gut are associated with adverse maternal and child health outcomes.  Vaginal Dysbiosis  The vaginal microbiome has received very little attention, despite the prevalence of bacterial vaginosis (BV) - occurs when the vaginal microbiome shifts into a dysbiotic, or unhealthy, state.  BV plagues approximately 30 percent of reproductive- age women in the United States; in some countries, more than 50 percent of women may be affected  Research indicates: vaginal microbiome may influence the propagation of sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV).  The healthy vaginal microbiome, in contrast, is often dominated by one of four Lactobacillus species: L. crispatus, L. iners and others  Of various Lactobacillus spp., L. crispatus seems to be associated with optimal health. “Crispatus is the golden child of all the lactobaccilli,  A microbiota dominated by L. iners has been linked to a greater risk for developing BV. Autoimmune diseases: Dysbiosis & Overreactions of Immune system Crohn’s disease Ulcerative colitis Diabetes type 1 Multiple sclerosis Lupus Rheumatoid arthritis Rheumatic fever  Concept Check-8 What are prebiotics? A. food rich in meat B. food deficient in fibers C. food that supports probiotics D. all  Concept Check-9 Which is one of the most modifiable factors to maintain eubiosis A. Genetics B. Old age C. Pregnancy D. Diet PATHOGENS & INFECTIONS Learning Outcomes: Section 11.2 4. Differentiate between colonization, infection, and disease. 5.Differentiate between pathogenicity and virulence. 6.Define opportunism. Contact, Infection, Disease: A Continuum Infectious Disease: the disruption of a tissue or organ caused by microbes or their products Contact progresses to infection and ends in disease Not all contacts lead to colonization Not all colonizations lead to infection Not all infections lead to disease Contamination without colonization and colonization without disease are the rule The Progress of Infection Pathogen: a microbe whose relationship with its host is parasitic and results in infection and disease Type and severity of infection depend on the pathogenicity of the organism and the condition of the host The Progress of Infection (cont’d) Pathogenicity: an organism’s potential to cause infection or disease True pathogens: capable of causing disease in healthy persons with normal immune defenses -generally associated with a specific, recognizable disease -may vary in severity from mild to severe to fatal -examples include the influenza virus, plague bacillus, and malarial protozoan  Virulence refers to the degree of pathogenicity of a microbe - determined by its ability to -establish itself in a host -cause damage Virulence factor: any characteristic or structure of the microbe contributing to its ability to establish itself in the host and cause damage (e.g., toxins or other  Opportunistic pathogens -cause disease when the host’s defenses are compromised -not considered pathogenic to a normal, healthy person -do not possess well-developed virulence properties -examples include Pseudomonas species and Candida albicans Learning Outcomes 7. List the various steps in causing disease by an organism 8. List several portals of entry & portals of exit 9. Define infectious dose. 10. Describe three ways microbes cause tissue damage How a disease is caused (Pathogenesis)? Step One: Becoming Established – Portals of Entry Portal of entry: the route that a microbe takes to enter the tissues of the body to initiate an infection Exogenous: microbe originating from a source outside the body from the environment or another person or animal  The Steps Involved When a Microbe Causes Disease in a Host Causing Damage Exiting Host Finding a Portal Attaching Firmly Surviving Host Defenses (disease) of Entry Direct damage Portals of exit Skin Fimbriae Avoiding phagocytosis Toxins and/or Respiratory tract, GI tract Capsules Avoiding death inside phagocyte enzymes salivary glands Respiratory tract Surface proteins Absence of specific immunity Indirect damage Skin cells Urogenital tract Viral spikes Inducing Fecal matter Endogenous biota inappropriate, Urogenital tract excessive host Blood response The Size of the Inoculum Infectious dose (ID) -the minimum number of microbes necessary to cause an infection to proceed -microorganisms with smaller infectious doses have greater virulence -ID for rickettsia is a single cell -ID for tuberculosis, giardiasis, and  -ID for gonorrhea is 1,000 cells -ID for typhoid fever is 10,000 cells -ID for cholera is 1,000,000,000 cells Step Two: Becoming Established – Attaching to the Host Adhesion -process by which microbes gain a more stable foothold on host tissues -dependent on binding between specific molecules on both the host and pathogen -pathogen is limited to only those cells (and organisms) to which it can – Attaching to the Host (cont’d) Adhesion mechanisms - fimbriae (pili) - surface proteins - adhesive slimes or capsules - viruses attach by specialized receptors - parasitic worms fastened by suckers, hooks, and barbs Step Three: Becoming Established – Surviving Host Defenses Microbes not established as normal biota will likely encounter the host immune defenses when first entering Phagocytes: cells that engulf and destroy host pathogens by means of enzymes and antimicrobial chemicals – Surviving Host Defenses (cont’d) Antiphagocytic factors -virulence factors that help pathogens to avoid phagocytes -leukocidins: kill phagocytes outright; Streptococcus and Staphylococcus  -slime or capsule: makes it difficult for the phagocyte to engulf the pathogen: Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis -some bacteria survive inside the phagocyte:Legionella, Mycobacterium, and many rickettsias Step Four: Causing Disease How Virulence Factors Contribute to Tissue Damage Virulence factors are the adaptations that a microbe uses to establish itself in a host Three ways that microorganisms cause damage to their host 1. directly through the action of enzymes 2. directly through the action of toxins (both endotoxins and exotoxins) 3. indirectly by inducing the host’s defenses to respond excessively or inappropriately Extracellular Enzymes Exoenzymes -enzymes (always proteins) secreted by microbes that break down and inflict damage on tissues -dissolve the host’s defense barriers to promote the spread of disease to other tissues  Examples of exoenzymes -mucinase: digests the protective coating on mucous membranes -hyaluronidase: digests the ground substance that cements animal cells together -coagulase: causes clotting of blood or plasma Learning Outcomes: Section 11.2 (cont’d) 7.Differentiate between endotoxins and exotoxins. 8. Describe different infections types 9.List different modes of transmission of infectious agents. 11.Define nosocomial infection, and list the Bacterial Toxins: A Potent Source of Cellular Damage Toxin: a specific chemical product of microbes, plants, and some animals that is poisonous to other organisms Toxins are named according to their target -neurotoxins act on the nervous system -enterotoxins act on the intestines -hemotoxins lyse red blood cells -nephrotoxins damage the kidneys Bacterial Toxins (cont’d) Exotoxins -proteins with a strong specificity for a target cell and extremely powerful, sometimes deadly effects -affect cells by damaging the cell membrane and initiating lysis and disrupting intracellular function  Hemolysins -disrupt the membrane of red blood cells to release hemoglobin -Streptococcus pyogenes produces streptoslysins -Staphylococcus aureus produces alpha and beta toxins  Endotoxin -lipopolysaccharide (LPS), part of the outer membrane of gram- negative cell walls -has a variety of systemic effects on tissues and organs -causes fever, inflammation, hemorrhage, and diarrhea -blood infections by Salmonella, Shigella, and Escherichia coli are particularly Three Ways Microbes Damage the Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Host Bacteria Enzymes Enzymes Cell Epithelial cell junction (a) Secreted enzymes destroy tissue. Toxins Exotoxins Endotoxin Clostridium tetani exotoxin travels to neurons in spinal column Tetanospasmin (b) Specific secreted protein binds to specific tissue target. Outer membrane component causes fever, malaise, aches, and shock. Inducing Host Defenses Bronchus Bronchiole Pneumococci Capsule Cell Alveoli Inflammatory exudate Capsule of Streptococcus pneumoniae keeps it from being phagocytosed; continued bacterial presence causes continued inflammation, especially fluid release into lungs. (c)  Concept Check-1 Which of the following are exoenzymes? A. Mucinase B. Coagulase C. LPS layer D. Hemolysin E. a, b  Concept Check-2 LPS (lipopolysaccharide) membrane in the Gram negative pathogen functions as… A. an exotoxin B. an exoenzyme C. a mucinase D. an endotoxin  Concept Check-3 John’s infection spread to several sites and tissue fluids. This type of infection is known as A. Systemic infection B. Chronic infection C. Focal infection D. Secondary infection  Exercise: 1. How would you differentiate between enzymes and toxins Exercise: 2. List two endotoxins Animals as Reservoirs and Sources (cont’d) Zoonosis -an infection indigenous to animals but naturally transmissible to humans -human is essentially a dead- end host -make up a full 70% of all new emerging diseases worldwide Common Zoonotic Infections Nosocomial Infections: The Hospital as Source of Disease Nosocomial infections: infections acquired or developed during a hospital stay -from 0.1 – 20% of all admitted patients, with an average of 5% -2 – 4 million cases a year, resulting in 90,000 deaths Most Common Nosocomial Infections Septicemia 6% Skin 8% Other (meningitis, Urinary tract gastroenteritis) 40% 12% Respiratory 15% Surgical sites 19%  Concept Check-4 Which of the following is the most common nosocomial infection? A. Septicemia B. UTI C. STD D. Respiratory tract infection