Modulate immune system to better recognize and respond to infectious agents.

Engineer microbiomes to induce immunological tolerance to certain antigens or dampen down the severity of immune responses.

• Technical Achievement: Engineer microbiomes that express interleukins in response to inflammatory cytokines and chemokines, to reduce the risk of illness caused by cytokine storms.
• Technical Achievement: Engineer microbiomes that facilitate phlegm and fluid transport out of the respiratory tract, to reduce the physiological impact of pneumonia.
• Technical Achievement: Engineer immunologically silent microbiomes that localize to heart tissues and express surface proteins that bind coxsackievirus and adenovirus receptor (CAR) proteins, to decrease incidence of myocarditis-inducing viral infections.

Engineer microbiomes to detect and degrade bacterial capsules in order to block immune evasion.

• Technical Achievement: Engineer microbiomes to produce capsule degrading proteins in response to capsule-containing pathogens.
• Technical Achievement: Engineer microbiomes that bind to and kill bacteria that produce specific capsule types.

Engineer microbiomes to increase immune sensitivity to infection.

• Technical Achievement: Engineer resident microbiomes that rapidly increase production of immunostimulatory molecules in response to pathogens (e.g., bacterial, viral, fungal, or parasitic), so an immune response can be mounted prior to establishment of infection.
• Technical Achievement: Engineer microbiomes so community members can bind to and be taken up with pathogens, to enable or inhibit cross-presentation of pathogen antigens.

Design prophylactic treatments that exclude pathogens and prevent or reduce virulence in opportunistic pathogens.

Modulate the gut microbiome to reduce the risk of diseases caused by pathogen invasion or colonization.

• Technical Achievement: Design microbiomes that exclude or kill cancer-causing bacteria (e.g., Fusobacterium nucleatum, Helicobacter pylori).
• Technical Achievement: Engineer gut microbes that can eliminate bacterial pathogens (e.g., Escherichia coli, Salmonella sp., Listeria monocytogenes) in a strain-specific manner using a variety of mechanisms (e.g., Type 6 secretion systems, antimicrobial peptides, microcins).
• Technical Achievement: Design microbiomes that deprive pathogenic gut enterobacteria of lumenal niches through exploitative and interference competition.
• Technical Achievement: Engineer gut microbiomes to constitutively produce antiviral compounds or to prevent viral adhesion to cells.

Engineer gut microbiomes to prevent toxin-mediated diseases/pathogens.

• Technical Achievement: Engineer microbiomes that degrade toxins before they can bind their target receptor in the gut.
• Technical Achievement: Engineer microbiomes that produce anti-toxin proteins to neutralize toxins and prevent foodborne diseases.

Engineer gut microbiomes to diminish virulence transitions in opportunistic pathogens.

• Technical Achievement: Engineer microbiomes that degrade quorum sensing molecules important for virulence transitions (e.g., agr cyclic peptides, acyl-homoserine lactones).
• Technical Achievement: Engineer microbiomes to prevent induction of inflammation or reduce inflammation after it is induced (e.g., facultative tetrathionate respiration capabilities to mitigate pathogenic effects of Salmonella species).
• Technical Achievement: Engineer microbiomes to produce toxin-binding, neutralizing proteins (e.g., mAb fragments against TcdAB).

Engineer skin microbiomes to repel biting and stinging insects.

• Technical Achievement: Engineer skin microbiomes to produce Xenorabdus spp.-derived mosquito repellant compounds.¹Kajla, M. K., Barrett-Wilt, G. A., & Paskewitz, S. M. (2019). Bacteria: A novel source for potent mosquito feeding-deterrents. Science Advances, 5(eaau6141), 11. View Publication
• Technical Achievement: Engineer skin microbiomes to kill or exclude mosquito-attracting microbial species.²Michalet, S., Minard, G., Chevalier, W., Meiffren, G., Saucereau, Y., Tran Van, V., Comte, G., Tran, F., & Valiente Moro, C. (2019). Identification of human skin bacteria attractive to the Asian Tiger mosquito. Environmental Microbiology, 21(12), 4662–4674. View Publication
• Technical Achievement: Engineer skin microbiomes to produce compounds that repel stinging insects (e.g., wasps, hornets).
• Technical Achievement: Engineer skin or surface-adherent microbiomes (e.g., to clothing, textiles, bed frames) that produce compounds that mask repel biting pests (e.g., ticks, fleas, lice, bedbugs, spiders).

Design microbiomes that enhance or replace existing medicines (e.g., drugs and vaccines) to protect against bacterial and viral pathogens.

Engineer microbiomes to produce macromolecular biologics.

• Technical Achievement: Engineer microbiomes that can colonize the gut, invade the gut epithelium, and produce antigens at will (e.g., engineer a universal vaccine platform for foodborne pathogens).
• Technical Achievement: Engineer microbiomes that secrete virus-trapping particles (e.g., liposomes, extracellular compartments) to reduce virus infectivity.

Engineer microbiomes to produce small molecule drugs.

• Technical Achievement: Engineer microbiomes that convert waste or inflammation-inducing molecules into pathogen-inhibiting compounds (e.g., butyrate to suppress Salmonella spp., antibiotics).
• Technical Achievement: Engineer gut microbiomes that compete with pathogens for essential molecules (e.g., secrete siderophores or chelators to sequester essential metal cofactors) without depleting the host of those same molecules.

Design microbiomes that use novel mechanisms to control infection.

• Technical Achievement: Engineer microbiomes that chemotax towards antibiotic degradation products and sequester essential molecules, to nutritionally outcompete antibiotic-resistant bacteria.
• Technical Achievement: Engineer microbiomes that express common cell-surface proteins used by pathogens to invade or enter cells, to reduce the likelihood of a successful infection.

Footnotes

1. Kajla, M. K., Barrett-Wilt, G. A., & Paskewitz, S. M. (2019). Bacteria: A novel source for potent mosquito feeding-deterrents. Science Advances, 5(eaau6141), 11. https://doi.org/10.1126/sciadv.aau6141
2. Michalet, S., Minard, G., Chevalier, W., Meiffren, G., Saucereau, Y., Tran Van, V., Comte, G., Tran, F., & Valiente Moro, C. (2019). Identification of human skin bacteria attractive to the Asian Tiger mosquito. Environmental Microbiology, 21(12), 4662–4674. https://doi.org/10.1111/1462-2920.14793