Review

. 2017 Jun:37:95-102.

doi: 10.1016/j.mib.2017.05.014. Epub 2017 Jun 14.

Next-generation precision antimicrobials: towards personalized treatment of infectious diseases

Cesar de la Fuente-Nunez¹, Marcelo Dt Torres², Francisco Jm Mojica³, Timothy K Lu⁴

Affiliations

¹ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA. Electronic address: cfuente@mit.edu.
² Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brazil.
³ Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Pavilion 12, 03080, Alicante, Spain.
⁴ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA. Electronic address: timlu@mit.edu.

PMID: 28623720
PMCID: PMC5669808
DOI: 10.1016/j.mib.2017.05.014

Review

Next-generation precision antimicrobials: towards personalized treatment of infectious diseases

Cesar de la Fuente-Nunez et al. Curr Opin Microbiol. 2017 Jun.

. 2017 Jun:37:95-102.

doi: 10.1016/j.mib.2017.05.014. Epub 2017 Jun 14.

Authors

Cesar de la Fuente-Nunez¹, Marcelo Dt Torres², Francisco Jm Mojica³, Timothy K Lu⁴

Affiliations

¹ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA. Electronic address: cfuente@mit.edu.
² Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brazil.
³ Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Pavilion 12, 03080, Alicante, Spain.
⁴ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Biophysics Program, Harvard University, Boston, MA, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA, USA. Electronic address: timlu@mit.edu.

PMID: 28623720
PMCID: PMC5669808
DOI: 10.1016/j.mib.2017.05.014

Abstract

Antibiotics started to be used almost 90 years ago to eradicate life-threatening infections. The urgency of the problem required rapid, broad-spectrum elimination of infectious agents. Since their initial discovery, these antimicrobials have saved millions of lives. However, they are not exempt from side effects, which include the indiscriminate disruption of the beneficial microbiota. Recent technological advances have enabled the development of antimicrobials that can selectively target a gene, a cellular process, or a microbe of choice. These strategies bring us a step closer to developing personalized therapies that exclusively remove disease-causing infectious agents. Here, we advocate the preservation of our beneficial microbes and provide an overview of promising alternatives to broad-spectrum antimicrobials. Specifically, we emphasize nucleic acid and peptide-based systems as a foundation for next-generation alternatives to antibiotics that do not challenge our microbiota and may help to mitigate the spread of resistance.

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Conflict of interest statement

Conflict of interest

The authors report no conflict of interests associated with this manuscript

Figures

**Figure 1. Precision antibiotics**
Hypothetical graphic showing treatment of specific disease causing bacterial infections with precision antimicrobials. For example, in the left side of the figure, we have an infection caused by the orange bacteria, which are surrounded by beneficial microbiota bacteria (colored in green and purple). In this scenario, a precision peptide designed to target the green pathogen will exclusively target this organism. The same applies to the other two examples, where peptides against green (center image) and purple bacteria (right image) would selectively remove these organisms.

**Figure 2. Personalized approach to infectious diseases**
Potential of precision antimicrobial strategies such as the ones described in this review (shown on the left of the figure) for personalized treatment of infectious diseases. In the future, early diagnostic methods may enable rapid identification of disease-causing pathogens, and precision antimicrobial agents may allow specific treatment of infection, while leaving non-causative, beneficial microbial communities unaffected. These advances, coupled with early-diagnostic tools for rapid detection of infectious agents, will constitute the foundation of personalized treatment of infectious diseases.

**Figure 3. Design principles for selective peptides**
Hypothetical images of modifications that can be made to generate precision peptides.

See this image and copyright information in PMC

References

1. Davies DS, Farrar J, Rex J, White LJ, RM . Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. In: JON, editor. The Review on Antimicrobial Resistance. 2014.
1. Trusts TPC. Antibiotics Currently in Clinical Development. 2016;2017
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1. Clemente JC, Ursell LK, Parfrey LW, Knight R. The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell. 2012;148:1258–1270. - PMC - PubMed

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Next-generation precision antimicrobials: towards personalized treatment of infectious diseases

Affiliations

Next-generation precision antimicrobials: towards personalized treatment of infectious diseases

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical