Microbial Interactions & Human Microbiota PDF

Assigned Reading of Date Topic Who OPENSTAX Ch 3. (92 – 93) DPS Ch 4. (13...

Assigned Reading of Date Topic Who OPENSTAX Ch 3. (92 – 93) DPS Ch 4. (131 – 138) Lecture 17: Ch 11. (453 – 454) 22) Th, March 27 Microbial interactions & Human Ch 17. (690 – 691) microbiota Ch 24 (1004 – 1006) Lecture 18: DPS 23) T, April 1 Ch 17. (683 – 724) Innate immunity Lecture 19: DPS 24) Th, April 3 Ch 18. (725 – 764) Adaptive immunity Ch 16. (651 – 676) DPS Lecture 20: Ch 18 (725 – 728; 750 25) T, April 8 Epidemiology & Vaccines – 758) Lecture 21: DPS 26) Th, April 10 Antimicrobial chemotherapy & Ch 14 (557 – 603) Drug resistance 27) T, April 15 EXAM 4 (lectures 17-21) DPS Microbial Interactions BIOL 351  Mutualism - A reciprocal benefit accrues to both partners  Mutualism Buchnera aphidicola and aphids http://schaechter.asmblog.org/schaechter/2009/09/good-guys-bad-guys.html  Buchnera aphidicola Gram-negative – 617kb genome (E. coli ~4.6 Mb) Lives in the aphid – Inside aphid cells à bacteriocytes (mycetocyte) Transmitted vertically from mother to daughter Braendel & Stern 2003  Buchnera aphidicola Bacteriocyte (also: mycetocyte) DAPI – Blue (DNA stain) Buchnera – Green (rRNA stained green) http://www.york.ac.uk /biology/units/symbios is/intra- symbiosis.html#b  Buchnera aphidicola Obligate mutualists  Buchnera aphidicola What does the aphid do for Buchnera? – The two have evolved together millions of years à ~75% of the Buchnera genome has been lost Aphid provides Buchnera with amino acids that Buchnera cannot make  Buchnera aphidicola So what does Buchnera do for the aphid? – “gnotobiotic” aphids (gnotobiotics = germ free) Grow normally provided a diet supplemented w/ amino acids Aphids cannot make Trp – Buchnera must synthesize & provide Trp for the aphid 11 12  Attenuation Attenuation (in genetics) is a proposed mechanism of control in some bacterial operons which results in premature termination of transcription and which is based on the fact that, in bacteria, transcription and translation proceed simultaneously.  Regulation of tryptophan regulation (Attenuation) Snyder & Champness Figure 12.24  1:2 causes short pause Snyder & Champness `Figure 12.25 Sufficient Trp ribosome covers 1 and part of 2 Snyder & Champness Figure 12.25 Absence of Trp ribosome stalls at trp codons 2:3 form No termination Snyder & Champness Figure 12.25  Attenuation Summary If Region 2 of the RNA pairs with Region 3 of the RNA – Nonterminating stem loop – Transcription continues If Region 3 of the RNA pairs with Region 4 of the RNA – Terminating stem loop forms – Transcription terminates Translation of the leader peptide affects which region pairs  Cooperation A reciprocal benefit accrues to both partners  Examples of cooperation Figure 32.8  Commensalism One symbiont (the commensal) benefits while the other (host) isn’t harmed or helped  Example of commensalism Staphylococcus epidermidis – Commonly found growing on skin – Consumes human waste (oils, water, salts, dead skin cells) while normally having no impact on human health  Predation One organism preys on another  Bdellovibrio Gram-negative bacteria that preys on other organisms – Enters the prey’s periplasmic space and feeds on the cytoplasmic contents Figure 15.40  Bdellovibrio replication Eksztejn & Varon 1977  Binary Fission or Synchronous Septation? Fenton & Sockett 2010  Parasitism The parasite benefits while the host is usually harmed  Amensalism The adverse effect that one organism has on another  Example of amensalism Streptomyces spp. – Produce many different antibiotics Therefore they are studied heavily in the hunt for novel therapeutics  Competition Two organisms try to acquire the same resource (location or nutrient)  Human microbiota Microbes that live in or on humans – Often commensals or mutualists  How many organisms make up the human microbiota? The human body contains ~1013 human cells and Conjunctiva ~ten times more microbial cells Outer ear Nose & Pharynx Mouth 1010 Stomach 1012 Skin Small Intestine 1014 Anterior urethra Vagina Large Intestine  Biofilm Biofilm – slime-encased aggregation of bacteria Composed of polysaccharide, protein, and extracellular DNA Figure 19.6  Staphylococcus aureus biofilm formation Cells attach to a surface The cells multiply to a confluent “lawn” of cells on the surface An “exodus” phase occurs and some cells leave Biofilm then matures into towers of cells Staphylococcus aureus biofilm formation requires nuclease to digest the extracellular DNA Moormeier & Bayles 2014 “Minimal gut microbiome” CAZymes = enzymes that break down carbohydrates (humans don’t possess these)  Human microbiota Not only provides nutrients for the host – The human microbiota also protects the body from invasion of harmful bacteria Pathogen: any disease producing microorganism  C. difficile Gram (+), spore-forming anaerobe Colonizes and infects people who have been treated with antibiotics Large problem in hospital and healthcare  C. difficile pathogenesis Antibiotic treatment Disruption of colonic microflora Exposure to C. difficile spores, germination and colonization Relapse Normal Colon Toxin Production Damage to colonic mucosa, inflammation & diarrhea Antibiotic treatment Pseudomembranous Colitis  TcdA & B Biology Reinke & von Eichel-Streiber 2007  C. difficile pathogenicity locus tcdR tcdB tcdE tcdA tcdC TcdC TcdR Figure 2.27  Sporulation pathway External signals for sporulation desiccation cell density Spo0A starvation SpoIIAB σF Signal from Signal from SpoIIE endospore mother cell P activates σE; triggers early synthesis of σG endospore in endospore Signal from Phosphate genes are and pro-σK in endospore removed by transcribed. mother cell. activates σK. σF is inactive SpoIIE. Inactive Active when bound Developing SpoIIAA SpoIIAA to SpoIIAB. endospore σF σF σG σG SpoIIAB SpoIIAA σE pro-σK σK σF is pro-σE binds released. SpoIIAB. Mother cell © 2015 Pearson Education, Inc. Figure 7.15 F recruits RNAP to induce the expression of proteins needed to activate E E recruits RNAP to induce the expression of proteins needed to activate G G recruits RNAP to induce the expression of proteins needed to activate K sE sF sEK sG sK sG  Spore morphology and germination Clostridium difficile Bacillus subtilis Lawley & Dougan 2009 Moir & Behravan 2002  Spore peptidoglycan Composed of 2 layers – A small inner layer of peptidoglycan that will make up the new cell wall upon germination – A larger layer of specialized peptidoglycan (cortex) Composed of NAG & NAM and muramic-delta-lactam Not as highly crosslinked as cell wall peptidoglycan Stages of germination Adapted from Setlow, P 2003 Germination Hashimoto & Conti 1969  C. difficile treatment options Current Therapy Alternative Therapies Vancomycin Toxoid Vaccine (failed Metronidazole Phase III clinical trial) Difficid (Fidaxomicin) Probiotics (hit or miss) Zinplava (Bezlotoxumab) Fecal Replacement (very successful)