SGM 2015 livenotes

Some notes from SGM 2015:

Microbiome session

Diabetes, obesity and gut microbiota
Patrice Cani 

1. Microbiota-host interactions play a major role in obesity

2. Intestinal MyD88 is a sensor switching host metabolism during fat feeding

3. Endocannabinoids are key players involved in the microbiota-host interaction

Intestinal epithelial ​MyD88 is a sensor switching host metabolism towards obesity according to nutritional status
http://www.nature.com/ncomms/2014/141205/ncomms6648/full/ncomms6648.html
  
The endocannaboid system links gut microbiota to adipogenesis.
http://www.ncbi.nlm.nih.gov/pubmed/20664638

Adipose tissue ​NAPE-PLD controls fat mass development by altering the browning process and gut microbiota
http://www.nature.com/ncomms/2015/150311/ncomms7495/full/ncomms7495.html

Test from Torsten, not at SGM. Looked like an interesting talk!


Bacterial persisters
Sophie Helaine

Many species form persisters - highly tolerant to Abx. Persister cels represent a small sub-population caused b phenotypic switch. E. coli in vitro persisters are non-replicating bacterial cels.

Background:
http://www.nature.com/nrmicro/journal/v9/n7/full/nrmicro2601.html

Bacterial persisters: formation, eradication, and experimental systems
http://dx.doi.org/10.1016/j.tim.2014.03.008

Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters
http://www.sciencemag.org/content/343/6167/204

5-10% of the non-replicating bacteria resume growth.

Toxin-antitoxin systems related to persistence of E. coli in vitro.

http://www.pnas.org/content/108/32/13206.abstract

Thoughts: how to link dead/alive/persistence state to metagenomics data (single cell RNA-Seq?)

http://www.ncbi.nlm.nih.gov/pubmed/20890840
http://www.ncbi.nlm.nih.gov/pubmed/16085863

Stephen Bentley

Pneumococcus human host-restricted, usually lives in nasopharynx.

No overall change in species prevalence post-CV7. Subtle effects on resistance- generally remain stable.

Population genomics of post-vaccine changes in pneumococcal epidemiology
http://www.nature.com/ng/journal/v45/n6/full/ng.2625.html

MDR not secret of success for antimicrobial resistance.

Association between high admixture and AMR previously shown
http://www.ncbi.nlm.nih.gov/pubmed/19520963

Consistency in recombination hotspots between lineages
http://www.nature.com/ng/journal/v46/n3/abs/ng.2895.html

Non-typeable clone most efficient recipient of DNA by recombination

http://www.ncbi.nlm.nih.gov/pubmed/25480686

MGEs in pneumococcal AMR
http://www.nature.com/ncomms/2014/141119/ncomms6471/abs/ncomms6471.html

Prophage insertion in comYC genes blocks recombination in IC1 - !

Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone
http://www.biomedcentral.com/1741-7007/12/49



Fleming Prize Lecture

Michael Brockhurst

Sex, Death and the Red Queen
http://www.sciencemag.org/content/333/6039/166.figures-only

Running with the Red Queen: the role of biotic conflicts in evolution
http://rspb.royalsocietypublishing.org/content/281/1797/20141382

Antagonistic coevolution accelerates molecular evolution.
http://www.ncbi.nlm.nih.gov/pubmed/20182425

Coevolution accelerates molecular evolution
Coevolution drives greater between-population divergence

In clinical samples:

Divergent, Coexisting, Pseudomonas aeruginosa Lineages in Chronic Cystic Fibrosis Lung Infections.
http://www.ncbi.nlm.nih.gov/pubmed/25590983

Highly parallel evolution of LES lineages: mexAB-oprM, creBCD, ampC, lasR, oprD, pmaA, etc. etc.

Rapid turnover of diversity within patients
http://www.ncbi.nlm.nih.gov/pubmed/21297072

Evidence for changes in diversity during exacerbations, and evidence for lineage ‘switching’ over time.

Single strain bacterial populations high diverse
Most diversity is present in individual sputum samples
Diversity in clinically important traits like AbR and secreted molecules
Genetic data shows parallel evolution and patient-patient transmission.

What’s driving diversification in CF lungs? (Immune system Abx, species interactions, etc.)

Phage?
http://www.nature.com/ismej/journal/vaop/ncurrent/full/ismej2014223a.html

Evolutionary adaptation to ASM environment by: 
- loss of motility structures esp flagellum
- mtabolic and biofilm changes

Adding temperate phages to artifiicial sputum medium selects for a different set of mutations than seen in CF in-host evolution, e.g. pili, Type 6 secretion, flagellum, quorum sensing, etc.

Phage insertions cause several parallel mutations.




AMR in South Asia
Stephen Baker

Return to pre-AMR era
http://www.sciencemag.org/content/347/6226/1064.full

S. Typhi: monomorphic

Emergence of fluoroquinolone resistance, independent hyrA mutations.

Fitness benefits in fluoroquinolone-resistantSalmonella Typhi in the absence of antimicrobial pressure.
http://elifesciences.org/content/2/e01229

A high‐resolution genomic analysis of multidrug‐resistant hospital outbreaks of Klebsiella pneumoniae
http://embomolmed.embopress.org/content/early/2015/02/17/emmm.201404767.abstract

K. pneumoniae is exceptional coloniser of surfaces, tubes, etc.

K. pneumoniae outbreak - two distinct lineages, acquired blaNDM-1. 



Longitude Prize

The test must: identify when antibiotics are needed and if they are which ones to use.

Test must be: needed, accurate, affordable, rapid (<30 min), easy-to-use, scalable, safe, a prototype must be available.

Easy-to-use: minimally invasive, easy to dispose, long expiration, heat stable, withstand transportation, minimum maintenance etc.



Modelling Clostridium difficile infection
Caroline Chilton 

In vitro human gut model: tripe chemostat system arranged in weir cascade, primerd with faecal slurry, validated against the caecal content of sudden death victims.

Antibiotics knock down Bifidobacterial populations. Bacteroides not affected by clindamycin but effected by vancomycin.

16S profiling matches colony counts well.

Observed diversity highest pre-antibiotic, lowest with recurrence. Fidaxomicin less effect on diversity than others.

http://link.springer.com/article/10.1007%2Fs002489900072

Biofilm human gut model using rods
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088396



Ebola 

Mutation rate and genotype variation of Ebola virus from Mali case sequences
http://www.sciencemag.org/content/early/2015/03/25/science.aaa5646

Epidemiological and viral genomic sequence analysis of the 2014 Ebola outbreak reveals clustered transmission
http://cid.oxfordjournals.org/content/early/2014/12/12/cid.ciu1131.short?rss=1

Michael Tunney, QUB

CF microbiome: culture studies shows significant numbers of anaerobes (similar to P. aeruginosa).

Healthy airway microbiome quite similar to CF microbiome — Streptococcus, haemophilus, Rothia etc. but don’t see Pseudomonas, Burkholderia etc.

Diversity decreased in CF

Diversity positively correlated with lung function
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045001

Decade-long bacterial community dynamics in cystic fibrosis airways
http://www.pnas.org/content/109/15/5809.short

Lung explant microbiome study
http://www.pnas.org/content/109/34/13769/F4.expansion.html

Healthy microbiome cannot be cultured in late-stage CF infection.


William Wade, Oral Microbiome

50% of oral bacteria are uncultivable

Human Oral Microbiome
http://jb.asm.org/content/192/19/5002.full

Most human oral bacteria are found only in the mouth, notable exception Fusobacterium nucleatum.

Intra-oral habitats have characteristic microbiota.

Diet has relatively little effect on oral microbiome.

Why do historical dental samples correlate diet with microbiome? A: Effect of dental hygeiene.



Willlem van Schaik

E. faecium and E. faecalis genetically distinct - penicillin resistant.

E. faecium clade A1 “clinical isolates” - highest mutation rate
E. faecium clade A2 “animal isolates” - medium mutation rate
E. faecium clade B “human commensal” - lowest mutation rate

Phylogeny of closely related strains: gene content mirrors phylogeny. Differences caused by gain/loss of plasmids and phage-like elenents.

Hospital ICU microbiota: characterised by outgrowth of Enterococcus on long stays

Sewage resistome




Zamin Iqbal

75 out of 1607 samples have minor resistance calls

100% resistance correection on MDR S. aureus



Ebola virus

Prior to 2013: ~20 outbreaks, ~1,600 deaths, 25-90% mortality rate, 5 Ebolavirus species

Filovirus epidemic in 1956 in Bili, DRC - first Ebola outbreak?
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2815%2970092-7/abstract

Emergence of Ebola
http://www.nejm.org/doi/full/10.1056/NEJMoa1404505

25000 cases, 10000 deaths

Burial rites: involve touching the bodies, washing them. Mobile phone connectivity make it easier to gather more relatives for funerals.