Three Types of Symbiotic Relationship - Mutualism o Organism 1 Benefits o Organism 2 Benefits o E.

g Bacteria in human colon - Commensualism o Organism Benefits o Organism 2 Neither benefits nor Harmed o E.g Staphylococcus on skin o Can be opportunistic microbes and become parasite if given the chance - Parasitism o Organism 1 Benefits o Organism 2 Harmed o E.g Tuberculosis bacteria in human lung More Types - Positive: Mutualism, Protocooperation and Commensualism - Negative: Predation, Parasitism, Amensualism, Competition Mutualism - Both partners benefit o E.g Bacteria of cow guts (Ruminants) which digest cellulose o E.g Ant/ Fungus/ Streptomyces o E.g Rhizobium Legumes o E.g Squid/ Vibrio - Relationship is extremely stable because the interatction is essential to both partners o Usually involves millions of years of co-evolution - However, there is no true obligate mutualistic relationships between humans and bacteria o Unless you consider mitochondria Commensualism - One partner benefits, the other one is neither harmed nor benefits o E.g Staphylococcus growing on skin - Tends to be a stable long lasting relationship - However, there is the possibility for the organism to become a opportunistic pathogen Parasitism - Host is harmed while the partner benefits - Unstable relationship - There are millions of microbes, but for humans only ~150 are microbial parasites of medical importance - Colonization by microbes depends on o Environment Temperature, pH, Nutrient availability, oxygen supply o Unique physical features of microbe

o o o o

E.g Structural, mechanical and biochemical characteristics Inocula Dose Incubation time of microbe Host Resistance How microbes adapt the environment

If being pathogenic results in an unstable relationship, where do new diseases come from? - Zoonotic Diseases o Microbes that are stable and harbored in animals can be transmitted to humans to cause disease Opportunistic Infections o E.g Malaria (Monkeys), transmitted by mosquito o E.g Toxoplasmosis (Cats), transmitted by ingestion o E.g Anthrax (Domestic Livestocks), transmitted by inhalation, direct contact Normal Bacterial Flora - Also termed normal or indigenous microbiota - Refers to the organisms that colonize the bodys surfaces without normally causing disease - Two Types of Normal Bacterial Flora o Resident microbiota (mostly commensalistic) o Transient microbiota - Bacteria normally inhabit surfaces o External Surface: Skin o Internal Surfaces: Intestines, nasal mucosa, oral cavity o Metagenomic of fecal samples indicate that there are 150 times as many different microbial genes in the gut than in the human genome - Bacterial Cells : Human Cells is about 10:1 Resident Microbiota - Many that can reside all over the body o Upper Respiratory Tract Staphylococcus and Streptococcus o Upper Digestive Tract Lactobacillus o Lower Digestive Tract (A lot) Enterococcus, Proteus, Shigella, Escherichia o Female Urinary and Reproductive Systems Staphylococcus and Streptococcus o Male Urinary and Reproductive Systems Staphylococcus and Streptococcus o Eyes and Skin Skin: Staphylococcus and Micrococcus Conjunctiva: Staphylococcus

Transient Microbiota - Remain in the body for only hours to months before disappearing - Found in the same regions as the resident microbiota o Common on skin where oil and dirt can retain bacteria non- specifically - Cannot persist in the body due to o Competition from other microorganisms o Eliminated by the bodys defense cells o Chemical or physical changes in the body Human Microbiome Project - Comprehensive analysis of microbial communities in and on humans - Surprising Results o Surprised by complexity, power and sheer number of microbes in our bodies o Microbes exist in lungs, previously thought to be sterile o Mouth has 500-1000 species and they are in specific communities Tongue, Gum and Teeth - Most microbes present in intestines o Major immune system present in intestines to learn self from foreign stuff How do we acquire Normal Microbiota? - Development in the womb is generally free of microorganisms (Axenic) - Microbiota begins to develop during the birthing process - Much of ones resident microbiota established during the first months of life o Breast feeding helps - Develops into a complex dynamic community in the intestine - Affected by many factors o Mode of delivery o Breast or formula fed o Diet or genetics? Development of Human Infant Intestinal Microbiota (Palmer et al.) - Results o In the first few days to months, microbiota of the gut is highly variable from infant to infant Appears to be determined by the particular bacteria to which the infant happens be exposed o The diverse communities become progressively more similar, converging toward a generic adult-like profile o Over time, bacteria that is the most highly adaptive to the gut take over o Anaerobic Bacteroides and Firmicutes dominate, Proteobacteria and aerobic gram- negative found to a small degree o Fungi and Archaea also detected Case Study: Monitor microbial composition of gut in infant over a period of 2.5 years - Questions to be addressed

o How does the diversity of the microbiota relate to the functional gene content of the microbiome over time? o How are the communities that constitute the microbiota structured? o How do changes in diets and events, such as antibiotic treatment, affect the succession and functions of bacteria consortia? Results o Significant events (e.g Illness, Diet change, antibiotic treatment) trigger significant changes in the infants intestinal microbiota

Is Normal Flora Essential? - Studies of Germ-free animals (gnotobiotic) show o Poorly developed lymphoid tissue o Low concentration of circulating antibodies o Very thin intestinal wall, enlarged cecum o Require dietary Vitamin K - Animals live their normal lifespan, but are abnormally susceptible to microbial disease - Conclusion o Beneficial Effects of Microbes Prevent colonization of dangerous bacteria Can stimulate immune system Aids in the synthesis of vitamin K (blood clotting) and vitamin B12 (red blood cell production, nervous system function) o Harmful Effects Create and opportunity for acquisition of genes encoding virulence factors via horizontal transmission Microbes can occasionally convert the chemicals into carcinogens Loss of Normal Flora can lead to disease - Individual species of commensals do not provide direct benefit - However, collectively, commensals benefit the host by competing against pathogenic microbes o Microbial Antagonism - If normal bacterial flora is wiped out, e.g by antibiotic therapy o Fungi take over Commensalistic usually, but if it takes over host it is very hard to remove because we do not have good drugs for it o Physiological changes to host occurs E.g Changes in pH due to loss of fermenting organisms o Yeasts are common causes of vaginal and oral infection under these circumstances Opportunists - Normal microbiota that can cause disease under certain circumstances o Cause disease when host immune system is compromised (HIV) or when physical barriers are weakened (Burn patients)

o Changes in relative abundance of normal microbiota may allow opportunity for a member to thrive and overpopulate and cause disease o Introduction of normal microbiota into unusual site in the body E.g Developmental stages that create new environments for colonization E.g New teeth Contamination vs. Infection vs. Disease - Contamination o Presence of microbes in or on the body - Infection o When the organism has evaded the bodys external defenses, multiplied and become established in the body - Disease o Only when the invading pathogen alters the normal functions of the body (Morbidity) Symptoms Subjective characteristics of the disease felt only be the patient Signs Objective manifestations of the disease that can be observed or measured by others Syndrome Group of symptoms and signs that characterize a disease or abnormal condition - Asymptomatic or Subclinical o Occurs when the infections lack symptoms but may still have signs of infection o Person can be a carrier and not manifest and pass disease to others Classifications of Infectious Disease - Many Methods of Classification o E.g The body system they affect o E.g Taxonomic group o E.g Longevity and severity o E.g How they spread to their host - Terms Used to classify infectious disease o Acute: Disease in which symptoms develop rapidly and runs its course fast o Chronic: Disease with usually mild symptoms that develop slowly and lasts a long time o Asymptomatic: Disease without symptoms o Latent: Disease that appears a long time after infection o Communicable: Disease transmitted from one host to another o Contagious: Communicable disease that is easily spread o Non-communicable: Disease arising from outside of hosts or from opportunistic pathogen

o Systemic infection: Widespread infection in many systems of the body, often travels in blood or lymph o Primary infection: Initial infection within a give patient o Secondary infection: Infections that follow primary infection, often by opportunistic pathogens Categories of Disease o Infectious Cause by an infectious agent E.g Colds, Influenza, Herpes o Iatraognic Caused by medical treatment or procedures Subgroup of hospital-acquired disease E.g Surgical error, yeast vaginitis resulting from antimicrobial therapy o Nosocomial Disease acquired in health care setting E.g Pseudomonas infection in burn patient

Etiology: Study of the cause of disease - Kochs Postulates o One must satisfy to these postulates to prove a particular pathogen causes a particular disease - Exceptions to Kochs Postulates o Using postulates is not feasible in all cases Some pathogens cannot be cultured in the laboratory Some disease are caused by a combination of pathogens and other cofactors Ethical considerations that prevent applying postulates to pathogens that require a human host o Difficulties in satisfying postulates Diseases that can be caused by more than one pathogen Some pathogens are ignored as potential causes of disease Steps to Disease for Bacterial Pathogens - Transmission from Reservoir to Host o Direct contact, airborne, waterborne, foodborne, vector - Breach first line of defense o Break in skin, ingestion, lung inhalation etc. o May need to be transported via the circulatory or lymphatic system - Escape the second line of defense o Innate (non-specific defense) - Colonize tissue o Either through continued growth vs. becoming dormant Modes of Transmission of an Infectious Disease - Transmission from either a reservoir or portal of exit - Reservoir

o Living or nonliving continuous source of infectious disease Transmission through o Contact: Direct or indirect o Vehicle: Air, food or water o Vector: Bites, bodies

Insect Vectors - Vector: Insect that transmits disease from one host to another o Do not contract disease, but microbe replicates, typically in the salivary gland or gut o Microbe transmitted through the bite or feces that enters the site of puncture - E.g Mosquitoes o Anopheles transmits Plasmodium that causes malaria o Aedes transmits flavivirus that cause yellow fever or dengue (some additional ones too) - E.g Ticks o Ixodes transmits Borrelia burgdorferi that causes Lyme disease Portals of Entry (Breaching the First line of Defense) - Skin o Enter through opening, cuts or insect bites o Others enter by burrowing into or digesting the outer layers of the skin o Parenteral Route: By injection - Mucous Membrane o Line the body cavities that are open to the environment o Provide a moist, warm environment that is hospital to pathogens Most common is through the respiratory tract Entry through nose, mouth or eyes o Pathogens able to survive the acidic pH of the stomach may use the gut as a route of entry - Placenta o Enters baby through placenta