Encapsulated fusion protein confers "sense and respond" activity to chitosan-alginate capsules to manipulate bacterial quorum sensing.
We demonstrate that "nanofactory"-loaded biopolymer capsules placed in the midst of a bacterial population can direct bacterial communication. Quorum sensing (QS) is a process by which bacteria communicate through small-molecules, such as autoinducer-2 (AI-2), leading to collective behaviors such as virulence and biofilm formation. In our approach, a "nanofactory" construct is created, which comprises an antibody complexed with a fusion protein that produces AI-2. These nanofactories are entrapped within capsules formed by electrostatic complexation of cationic (chitosan) and anionic (sodium alginate) biopolymers. The chitosan capsule shell is crosslinked by tripolyphosphate (TPP) to confer structural integrity. The capsule shell is impermeable to the encapsulated nanofactories, but freely permeable to small molecules. In turn, the capsules are able to take in substrates from the external medium via diffusion, and convert these via the nanofactories into AI-2, which then diffuses out. The exported AI-2 is shown to stimulate QS responses in vicinal Escherichia coli. Directing bacterial population behavior has potential applications in next-generation antimicrobial therapy and pathogen detection. We also envision such capsules to be akin to artificial "cells" that can participate in native biological signaling and communicate in real-time with the human microbiome. Through such interaction capabilities, these "cells" may sense the health of the microbiome, and direct its function in a desired, host-friendly manner.
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, USA.
Apoorv
A
Gupta
Jessica L
JL
Terrell
Rohan
R
Fernandes
Matthew B
MB
Dowling
Gregory F
GF
Payne
Srinivasa R
SR
Raghavan
William E
WE
Bentley
D000464:Alginates / Q000737:chemistry; D000818:Animals; D000906:Antibodies; D057005:Bioengineering / Q000379:methods*; D002417:Cattle; D048271:Chitosan / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology*; D020723:Glucuronic Acid / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006714:Homoserine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D053769:Nanocapsules; D036103:Nanotechnology / Q000379:methods*; D011122:Polyphosphates; D053038:Quorum Sensing / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D012435:S-Adenosylhomocysteine; D012710:Serum Albumin, Bovine / Q000737:chemistry
D000464:Alginates; D000906:Antibodies; D006603:Hexuronic Acids; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D053769:Nanocapsules; D011122:Polyphosphates; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012710:Serum Albumin, Bovine; D006714:Homoserine; D020723:Glucuronic Acid; D048271:Chitosan; D012435:S-Adenosylhomocysteine; C005692:triphosphoric acid