TY - JOUR
T1 - Microarray analysis of the Escherichia coli response to CdTe-GSH Quantum Dots
T2 - Understanding the bacterial toxicity of semiconductor nanoparticles
AU - Monrás, Juan P.
AU - Collao, Bernardo
AU - Molina-Quiroz, Roberto C.
AU - Pradenas, Gonzalo A.
AU - Saona, Luis A.
AU - Durán-Toro, Vicente
AU - Órdenes-Aenishanslins, Nicolás
AU - Venegas, Felipe A.
AU - Loyola, David E.
AU - Bravo, Denisse
AU - Calderón, Paulina F.
AU - Calderón, Iván L.
AU - Vásquez, Claudio C.
AU - Chasteen, Thomas G.
AU - Lopez, Desiré A.
AU - Pérez-Donoso, José M.
N1 - Funding Information:
This work was supported by FONDECYT 11110077 (JMP), FONDECYT 11110076 (DB), FONDECYT 1130362 (CV), Anillo ACT 1107 (JMP), Anillo ACT 1111 (JMP, DB), UNAB DI 488-14/R (JMP), and CINV Millennium Initiative 09-022-F (Chile) (JMP). A doctoral fellowship from CONICYT to JPM is also acknowledged. TGC and DAL gratefully acknowledge support from the Robert A. Welch Foundation (X-011).
Publisher Copyright:
© 2014 Monrás et al.
PY - 2014/12/12
Y1 - 2014/12/12
N2 - Background: Most semiconductor nanoparticles used in biomedical applications are made of heavy metals and involve synthetic methods that require organic solvents and high temperatures. This issue makes the development of water-soluble nanoparticles with lower toxicity a major topic of interest. In a previous work our group described a biomimetic method for the aqueous synthesis of CdTe-GSH Quantum Dots (QDs) using biomolecules present in cells as reducing and stabilizing agents. This protocol produces nanoparticles with good fluorescent properties and less toxicity than those synthesized by regular chemical methods. Nevertheless, biomimetic CdTe-GSH nanoparticles still display some toxicity, so it is important to know in detail the effects of these semiconductor nanoparticles on cells, their levels of toxicity and the strategies that cells develop to overcome it. Results: In this work, the response of E. coli exposed to different sized-CdTe-GSH QDs synthesized by a biomimetic protocol was evaluated through transcriptomic, biochemical, microbiological and genetic approaches. It was determined that: i) red QDs (5 nm) display higher toxicity than green (3 nm), ii) QDs mainly induce expression of genes involved with Cd+2 stress (zntA and znuA) and tellurium does not contribute significantly to QDs-mediated toxicity since cells incorporate low levels of Te, iii) red QDs also induce genes related to oxidative stress response and membrane proteins, iv) Cd2+ release is higher in red QDs, and v) QDs render the cells more sensitive to polymyxin B. Conclusion: Based on the results obtained in this work, a general model of CdTe-GSH QDs toxicity in E. coli is proposed. Results indicate that bacterial toxicity of QDs is mainly associated with cadmium release, oxidative stress and loss of membrane integrity. The higher toxicity of red QDs is most probably due to higher cadmium content and release from the nanoparticle as compared to green QDs. Moreover, QDs-treated cells become more sensitive to polymyxin B making these biomimetic QDs candidates for adjuvant therapies against bacterial infections.
AB - Background: Most semiconductor nanoparticles used in biomedical applications are made of heavy metals and involve synthetic methods that require organic solvents and high temperatures. This issue makes the development of water-soluble nanoparticles with lower toxicity a major topic of interest. In a previous work our group described a biomimetic method for the aqueous synthesis of CdTe-GSH Quantum Dots (QDs) using biomolecules present in cells as reducing and stabilizing agents. This protocol produces nanoparticles with good fluorescent properties and less toxicity than those synthesized by regular chemical methods. Nevertheless, biomimetic CdTe-GSH nanoparticles still display some toxicity, so it is important to know in detail the effects of these semiconductor nanoparticles on cells, their levels of toxicity and the strategies that cells develop to overcome it. Results: In this work, the response of E. coli exposed to different sized-CdTe-GSH QDs synthesized by a biomimetic protocol was evaluated through transcriptomic, biochemical, microbiological and genetic approaches. It was determined that: i) red QDs (5 nm) display higher toxicity than green (3 nm), ii) QDs mainly induce expression of genes involved with Cd+2 stress (zntA and znuA) and tellurium does not contribute significantly to QDs-mediated toxicity since cells incorporate low levels of Te, iii) red QDs also induce genes related to oxidative stress response and membrane proteins, iv) Cd2+ release is higher in red QDs, and v) QDs render the cells more sensitive to polymyxin B. Conclusion: Based on the results obtained in this work, a general model of CdTe-GSH QDs toxicity in E. coli is proposed. Results indicate that bacterial toxicity of QDs is mainly associated with cadmium release, oxidative stress and loss of membrane integrity. The higher toxicity of red QDs is most probably due to higher cadmium content and release from the nanoparticle as compared to green QDs. Moreover, QDs-treated cells become more sensitive to polymyxin B making these biomimetic QDs candidates for adjuvant therapies against bacterial infections.
KW - Cadmium
KW - Nanoparticles
KW - Oxidative stress
KW - Toxicity mechanism
KW - Transcriptomic response
UR - http://www.scopus.com/inward/record.url?scp=84924292741&partnerID=8YFLogxK
U2 - 10.1186/1471-2164-15-1099
DO - 10.1186/1471-2164-15-1099
M3 - Article
C2 - 25496196
AN - SCOPUS:84924292741
SN - 1471-2164
VL - 15
JO - BMC Genomics
JF - BMC Genomics
IS - 1
M1 - 1099
ER -