Bacteriophages as Regulators of the Mammalian Microbiome JOSEPH FRANCIS 2018 ICC

Transcription

1 Bacteriophages as Regulators of the Mammalian Microbiome JOSEPH FRANCIS 2018 ICC

2 BIOMATRIX

3 BIOMATRIX (organosubstrate ICC 2003)

4 BIOMATRIX microbiota virobiota

5 BIOMATRIX microbiota microbiome virobiota virome

6 Microbiome Virome biosphere

7 BIOMATRIX theory viruses?

8 BIOMATRIX theory viruses? -delivery agents

9 Mammalian virome

10 Mammalian virome

11 X 100 trillion Approximate numbers of viruses in humans 6 5 bacteriophage animal plant archeal bacterial

12 Facts about phages infections/sec globally

13 Facts about phages infections /sec globally global carbon cycle cyanobacteria + cyanophage

14 Facts about phages infections /sec globally global carbon cycle repository of genes vitamins stress response proteins nucleic acid metabolism virulence factors chemotaxis proteins

15 Facts about phages infections /sec globally global carbon cycle repository of genes vitamins stress response proteins nucleic acid metabolism virulence factors chemotaxis proteins

16 Facts about phages 2.5 BILLION novel phage encoded genes in the biosphere!!

17 What are all these phages doing in mammals and humans?

18 What are all these phages doing in mammals and humans? population control

19 What are all these phages doing in mammals and humans? population control host protection organismal (mammalian)

20 What are all these phages doing in mammals and humans? population control host protection organismal (mammalian) bacterial (microbiome)

21 What are all these phages doing in mammals and humans? population control (known) host protection organismal (mammalian) (known) bacterial (microbiome) (unknown)

22 phage cloaking model flows from the biomatrix creation model

23 There are two parts to the phage cloaking model genome guarding immune system shielding

24 There are two parts to the phage cloaking model genome guarding immune system shielding Data for both of these concepts has been accumulating for decades but the concepts have been been undiscovered or ignored because of a focus on the complexity of genetic function which was originally studied using phages.

25 genome guarding -phage life cycles lysis lysogeny

26 genome guarding Esther Lederberg λ phage

27 λ phage

28 lysis lysogeny UV light

29 proposed model E.coli UV light

30 proposed model carcinogen UV light mutagen mutagen

31 proposed model carcinogen UV light mutagen mutagen

32 Add a Slide Title - 3

33 Surprising that nothing is documented about lambda phage protection of the microbiome especially since proteins which are known as guardians of the genome exist (?)

34 immune system shielding

35 Immune system shielding

36 What is Gram-negative sepsis? Sepsis is a medical condition in which the entire body experiences inflammation as it tries to fight off an infection that has made its way into the bloodstream. Gram-negative sepsis is the result of a Gram-negative bacterial infection. It is a potentially life-threatening condition that most commonly affects young children and older adults.

37 Marian Brida de Costa Loses Hands and Feet Fighting for Life

38 There are only a few classes of innate immune receptors and most interact with only a few ligands found mainly on bacteria and viruses.

39 proposed model E.coli UV light

40 proposed model E.coli UV light Phage coating

41 proposed model carcinogen E.coli UV light UV light mutagen mutagen Phage coating

42 proposed model carcinogen UV light mutagen mutagen

43 proposed model carcinogen UV light mutagen mutagen

44 FACTS WHICH SUPPORT PHAGE CLOAKING THEORY Phages are abundant in mammals and coexist with the microbiome and appear to maintain microbiome populations Commensual microbiome bacteria contain surface molecules like LPS which can be life threatening if released in the mammalian or human body Phages appear to coat microbiome bacteria protecting them from immune detection Phages possess designs to thoroughly coat disease causing molecules found on the surface of commensual bacteria Phages are found primarily in a lysogenic NOT lytic state in the mammalian microbiome preserving the microbiome by guarding the genome Phages in the lysogenic state prevent the microbiome from subsequent phage infection Phages possess designs to prevent genetic alteration of microbiome bacteria Phages help to protect and preserve both of their hosts within the mammalian body and microbiome Phages possess designs to maintain commensual microbiome bacteria but also destroy pathogenic invaders

45 FACTS WHICH SUPPORT PHAGE CLOAKING THEORY Based on observations of E.coli, multiple species of phage can attach to a single type of bacteria promoting the thorough coating of microbiome bactera We propose that once lysed, microbiome bacteria parts and virulence factors can remain coated by phage preventing life threatening sepsis reactions The mammalian immune system possesses designs to preserve phages by interacting primarily with animal viruses to destroy them and NOT phage