Holobionts and Their Hologenomes

The 2015 American Society of Microbiology general meeting kicks off on Sunday in New Orleans (#ASM2015 for Tweeters). The agenda looks incredible (as usual, ASM is one of the best conferences of the year), and I am very excited to announce the Monday 2pm session: "Holobionts and Their Hologenomes". As far as I am aware, it is the first symposium for the topic at a major society meeting. We've got a great gender balance of speakers, including the headliners and pioneers in the area, Eugene and Ilana Rosenberg. We're missing many other pioneers who I wished to include, but alas the session is populated by senior and junior investigators and students - the way ASM likes it and it should be. We should work to have a future meeting solely on the topic. My thanks to all of the speakers and session shepherds Joerg Graf and Ned Ruby for their input along the way. If you're going to ASM, stop by Room 260 on Monday at 2pm. 

I believe this session and scholarship echoes the sentiment expressed by the late Carl Woese when he wrote in 2004: 

"The time has come to replace the purely reductionist eyes down molecular perspective with a new and genuinely holistic, eyes up, view of the living world, one whose primary focus is on evolution, emergence, and biology's innate complexity." 

Though instead of "replace", "unify" works best. 

Convener6/1/2015 2:00:00 PMSeth Bordenstein; Vanderbilt Univ., Nashville, TN

Presentations: From the First Eukaryote to Man: The Hologenome Concept6/1/2015 2:00:00 PMEugene I. Rosenberg and I. Zilber-Rosenberg; Tel Aviv Univ., Tel Aviv, Israel Nerve Cells are Involved in Maintenance of the Hydra Holobiont6/1/2015 2:30:00 PMKatja Schroder; Zoological Inst., Kiel, Germany A Critical Role of the Plant Microbiome for Immunocompetency6/1/2015 2:45:00 PMJ. M. Kremer1, B. Kvitko1, J. P. Jerome1, J. M. Tiedje1, S. He2;  1Michigan State Univ., East Lansing, MI, 2Howard Hughes Med. Inst., East Lansing, MI Sponge Hologenomics: Unlocking the Ianthella basta Symbiome6/1/2015 3:00:00 PMNicole Webster; Australian Inst. of Marine Sci., Townsville, Australia Amphibian-Microbial Symbiosis: Unraveling the Role of Host Species, Habitat, and the Pathogen Batrachochytrium dendrobatidis on Skin Bacterial Community Structure6/1/2015 3:30:00 PME. A. Rebollar Caudillo1, M. Hughey2, D. Medina2, S. Loftus2, L. L. House2, R. N. Harris1, L. K. Belden2;  1James Madison Univ., Harrisonburg, VA, 2Virginia Tech, Blacksburg, VA Microbe-Cycling in Tree Sloths Facilitated by Pyralid Moths6/1/2015 3:45:00 PMK. A. Dill-McFarland1, J. N. Pauli1, M. Z. Peery1, P. J. Weimer1,2, G. Suen1;  1Univ. of Wisconsin-Madison, Madison, WI, 2USDA Agricultural Res. Service, Madison, WI It Takes a Village: Community Interactions in the Fungus-Growing Ant Symbiosis6/1/2015 4:00:00 PMJonathan L. Klassen; Univ. of Connecticut, Storrs, CT

Ridding bacteria of antibiotic resistance by gene editing

Really interesting development for research on antibiotic resistance and "phage therapy".... (Source and research article)

Targeting Antibiotic-Resistant Bacteria with CRISPR and Phages

Researchers develop a CRISPR-based, two-phage system that sensitizes resistant bacteria to antibiotics and selectively kills any remaining drug-resistant bugs. 

By Anna Azvolinsky | May 18, 2015

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WIKIMEDIA, DR GRAHAM BEARDSUsing bacteriophages to deliver a specific CRISPR/Cas system into antibiotic-resistant bacteria can sensitize the microbes to the drugs, according to a study published this week (May 18) in PNAS. The approach, developed by Udi Qimron of Tel Aviv University and his colleagues, is a modified version of phage therapy that does not require the delivery of phages to infected tissues and could help offset the pressure on bacterial populations to evolve drug resistance, according to the team.

Unlike classic phage therapy, which uses one or more types of phages to infect and lyse specific bacterial strains, the crux of this new approach is using these specialized viruses to supply CRISPR/Cas to rid bacteria of antibiotic-resistance plasmids in the environment before the microbes are able to infect a host. Each phage is specific to a bacterial species or strain and, using CRISPR, researchers can target a specific bacterial sequence.

“The CRISPR technique is at the heart of [this work],” said Michael Terns, a research professor of biochemistry, molecular biology, genetics, and microbiology at the University of Georgia who was not involved in the work. “It’s a nice application of the CRISPR system to attack resistance genes using phage as a vehicle.”

“The classic phage approach doesn’t distinguish between bacteria that are truly pathogenic versus their very similar neighbors,” said Timothy Lu, a professor of biological and electrical engineering at MIT who was not involved in the work. “The idea of CRISPR-based approaches is to enact sequence-specific antimicrobial activity, placing selective pressure against genes that are bad rather than conserved bacterial targets.”

Qimron and his colleagues first created an E. coli-targeting lambda phage that encodes the CRISPR genes plus spacers that target two conserved β lactamases, enzymes that confer resistance to β-lactam antibiotics. Once integrated into the E. coli genome, the phage prevented the transfer of β lactamase-encoding plasmids and could also delete these plasmids from individual bacterial cells. These lambda phage-encoding bacteria become sensitive to treatment with antibiotics.

The researchers then inserted the same β lactamase-targeting spacer sequences into lytic phages that cause bacterial cell lysis. When the lytic phage enters an E. coli cell encoding the CRISPR-phage, its DNA is cleaved, conferring a survival advantage for the antibiotic-sensitive bacteria. In the presence of the lytic phages, bacteria that don’t receive the CRISPR treatment are killed by the lytic phage. “Adding the lytic phages changes the selective pressure in the environment so that sensitive bacteria are favored over the resistant bacteria,” explained Qimron.

His team was not the first to use this approach. Lu and his colleagues last year showed that they could kill antibiotic-resistant bacteria using phages that transferred an antibiotic-resistance targeting CRISPR/Cas system. Another group showed that the CRISPR/Cas9 system could be used reduce the colonization of skin by virulent Staphylococcus aureus in a mouse model.

Among the potential limitations of this approach, “finding a phage for each pathogenic strain is something that has to be worked out,” Terns told The Scientist.

Qimron’s team will next try to apply this CRISPR/phage system on Pseudomonas aeruginosa—one of the world’s most prevalent antibiotic-resistant pathogens that cause hospital-acquired infections—and test whether bacterial sensitization works in a more complex microbial environment—the mouse cage.

While promising, the approach does not address the development of antibiotic resistance. Lu noted that resensitizing drug-resistant bacteria is only a piece of the puzzle. “The way I view it is not that we will be able to make an evolution-proof therapy, but that the genetic engineering tools will become more robust so that as evolution happens, we can rapidly develop countermeasures,” he said. “It will be very hard to make evolution-proof therapy, there is just too much pressure for the bacteria to survive.”

I. Yosef et al., “Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria,” PNAS, doi:10.1073/pnas.1500107112, 2015. 

Mothers, Infants, and The Microbiome

New study from Sweden on the microbiome in the first year of life shows that:

•Gut microbiomes of 98 mothers and their infants during the first year of life was assessed

•Cessation of breast-feeding drives the maturation of the infant gut microbiome

•Shifts in signature species demonstrate nonrandom transitions in the infants’ gut

•Changes in nutrient and xenobiotic metabolism mark maturation of the gut microbiome

(Source) Like babies themselves, the intestinal microbiomes of infants start out in an immature state and over time grow into communities similar to those of adults. In a new survey of 98 Swedish babies whose microbiota were sampled several times during their first year of life, researchers found that the microbiomes of breastfed infants persisted in a “younger” state longer than those of non-breastfed babies, even after the introduction of solid foods.

The conclusion that “stopping breastfeeding—rather than introducing solids—drives maturation is a new idea, because we all thought so far that solids introduction was a key factor in changing the microbiota,” said Maria Gloria Dominguez-Bello, a microbiologist at New York University School of Medicine who did not participate in the study.

Researchers from University of Gothenburg in Sweden and their colleagues found more adult-like taxa in the microbiomes of babies who stopped breastfeeding earlier, while the microbiota of babies breastfed for longer were dominated by bacteria present in breastmilk. The results, published today (May 13) in Cell Host & Microbe, are part of an effort to catalog the microbial changes that occur as children age and to note how those changes correlate with health and disease. Fredrik Bäckhed of Gothenburg and his colleagues collected stool samples from 98 moms and their newborns, and again sampled the babies’ stool at four and 12 months.

Unlike other studies that identified babies’ gut microbial taxa using 16S sequencing, Bäckhed’s team took advantage of metagenomic shotgun sequencing, which can be used to pick up on previously unknown microbes. “We have identified more than 4,000 new microbial genomes” as part of this project, Bäckhed told The Scientist.

Confirming previous work, his team’s analysis found that the 15 babies born via cesarean section were colonized by different bacteria—many from oral and skin communities—than babies born vaginally, who shared numerous microbes with those present in their mothers’ stool.

Because shotgun sequencing enabled the group to examine genes prevalent in the microbiome, Bäckhed’s team looked at the functionality of the intestinal microbiota as babies transitioned to different foods. For instance, in the vaginally delivered newborns’ microbiomes, genes that break down sugars in breastmilk were common. As these babies celebrated their first birthdays, the genes in their microbiomes favored the ability to breakdown starches, pectins, and more complex sugars.

“What’s nice about this paper is that they show this maturation [of the microbiome] in normal, healthy kids in a Western population follows this transition based on diet,” said Steven Frese, a postdoc at the University of California, Davis, who penned a commentary accompanying the study with his advisor, David Mills. “Being exposed to new foods promotes the growth of new bacteria that can consume them,” Frese told The Scientist.

However, as the authors noted in their study, “the increased capacity to degrade polysaccharides promoted by the introduction of solid foods did not become apparent until the infants stopped breast-feeding.” In other words, continued breastfeeding appeared to tamp down the functional changes in the microbiome that occured as the babies were exposed to new foods.

Bäckhed said the study cannot determine whether any particular microbial profile is better for babies than another. “The healthy microbiome probably covers a wide spectrum,” he said. “We can’t say who is predisposed to disease.”

He is continuing to follow the children as they get older to observe whether alterations in microbial communities are associated with disease. “This is quite an extensive characterization of the microbiome at some critical points during the first year of life that sets a basis for future research.”

F. Bäckhed et al., “Dynamics and stabilization of the human gut microbiome during the first year of life,” Cell Host & Microbe, 17:690–703, 2015.