Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Export

@article{citeulike:4134540, abstract = {Antimicrobial drug development is increasingly lagging behind the evolution of antibiotic resistance, and as a result, there is a pressing need for new antibacterial therapies that can be readily designed and implemented. In this work, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly targeted by antibiotics. We show that suppressing the SOS network in Escherichia coli with engineered bacteriophage enhances killing by quinolones by several orders of magnitude in vitro and significantly increases survival of infected mice in vivo. In addition, we demonstrate that engineered bacteriophage can enhance the killing of antibiotic-resistant bacteria, persister cells, and biofilm cells, reduce the number of antibiotic-resistant bacteria that arise from an antibiotic-treated population, and act as a strong adjuvant for other bactericidal antibiotics (e.g., aminoglycosides and beta-lactams). Furthermore, we show that engineering bacteriophage to target non-SOS gene networks and to overexpress multiple factors also can produce effective antibiotic adjuvants. This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants.}, author = {Lu, Timothy K. and Collins, James J.}, citeulike-article-id = {4134540}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0800442106}, citeulike-linkout-1 = {http://www.pnas.org/content/0800442106v1//.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/0800442106v1//.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19255432}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19255432}, day = {24}, doi = {10.1073/pnas.0800442106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {phage, synthetic\_biology, therapy}, month = {March}, number = {12}, pages = {4629--4634}, posted-at = {2009-03-05 08:30:36}, priority = {2}, title = {Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy.}, url = {http://dx.doi.org/10.1073/pnas.0800442106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4134540 L3 - citeulike-article-id:4134540 N2 - Antimicrobial drug development is increasingly lagging behind the evolution of antibiotic resistance, and as a result, there is a pressing need for new antibacterial therapies that can be readily designed and implemented. In this work, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly targeted by antibiotics. We show that suppressing the SOS network in Escherichia coli with engineered bacteriophage enhances killing by quinolones by several orders of magnitude in vitro and significantly increases survival of infected mice in vivo. In addition, we demonstrate that engineered bacteriophage can enhance the killing of antibiotic-resistant bacteria, persister cells, and biofilm cells, reduce the number of antibiotic-resistant bacteria that arise from an antibiotic-treated population, and act as a strong adjuvant for other bactericidal antibiotics (e.g., aminoglycosides and beta-lactams). Furthermore, we show that engineering bacteriophage to target non-SOS gene networks and to overexpress multiple factors also can produce effective antibiotic adjuvants. This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants. IS - 12 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 4634 TI - Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. VL - 106 SP - 4629 KW - phage KW - synthetic_biology KW - therapy AU - Lu, Timothy AU - Collins, James PY - 2009/03/24/ UR - http://dx.doi.org/10.1073/pnas.0800442106 ER -