Microbial Interactions with Humans

1. Microbial Interactions with Humans Disease = any change in state of health resulting in an inability to carry out normal function. Pathogen = an organism, virus or other agent capable of causing disease. Infectious Disease = a disease caused by a pathogen’s infection. Infection = invasion and growth of a microorganism in the host’s body. Pathogenicity = the ability to cause disease by overcoming host defenses. Virulence = a degree or intensity of pathogenicity; invasiveness and evasiveness of pathogen. Resistance = the hosts ability to prevent disease; defensiveness (antonym = susceptibility). Basic Definitions Ecological Interactions Normal Microbiota Infectious Diseases

2. Ecological Interactions Between Populations

4. Gnotobiotic Animals as Models “Germ” free animals provide controlled conditions for studies of microbe-host interactions. gnoto = Greek known Comparisons between animals with normal microbiota and gnotobiotic animals leads to insight on the role of specific microbes, or known consortia of microbes in animal health (good and bad). Gnotobiotic chicks used to demonstrate the nutritional importance of digestive microorganisms (1912).

5. Normal Microbiota*: *Transient Microbiota: Microbes that are present for a short time and don’t cause disease. * Knowledge of where and which microbiota normally reside assists medical professionals in predicting and interpreting clinical conditions of infection; they may stimulate host immune response.

7. Microbial AntagonismBacteria of normal microbiota has a negative effect on opportunistic and/or pathogenic bacteria. • Non-pathogen = mutualism, neutral interactions with host. • Opportunist Pathogens = commensalism with host shifts to parasitism when environmental conditions change that favor growth. • Primary Pathogens = parasitic upon first interaction with host. • Examples of Microbial Antagonism as a host defense in resisting infections disease: • Non-pathogens or commensal microbes interfer with growth of other microbes. • Escherichia colibacteriocins (lethal protein to related bacteria) prevents growth of Shigella spp. • Large intestine community prevents growth of Clostridium difficile (cause of psuedomembranous enterocolitis; necrosis of epithelial cells; bloody stools) • Vaginal community prevents growth of Candida albicans (“yeast infections”) • Propionibacterium acnes prevents growth of some Gram- pathogens.

8. “The Zit Story”: Shift to an Opportunistic Pathogen Skin can be a dry, acidic and saline environment, where inhibitory agents are excreted directly or indirectly and cell layers are constantly shed. P. acnes grows normally on normal supplies of sebum lipids; releasing unsaturated fatty acids toxic to Gram- bacteria (microbial antagonism). Hormones stimulate sebum production, inflammation, comedo formation resulting in acne vulgaris. Propionibacterium. acnes is most sensitive to tetracycline!

9. Opportunistic and Pathogenic Microorganisms Community shifts away from mutualism and commensalism and toward parasitism; favors the disease. Conversely, shifts away from parasitism to commensalism and mutualism; favors an improved state of health. What influences either such shifts in microbial-host interactions?

10. Infections disease versus good health in the host depends on the balance between microbial virulence level and abundance versus the status of host defense mechanisms (resistance). Infectious Disease ≈ (Virulence * Abundance)/Resistance

11. Overview of Host Defenses • Effectiveness of host resistance depends on three lines of defense. • If the first line of defense is breeched, elements of the second line of defense are engaged. • The second line of defense may establish conditions to speed up its defense processes by initiating the third line of defense. • Third line of defense is both cellular and humeral (antibody) mediate. (neutrophiles)