The Mylonakis lab uses a variety of tools to answer complex scientific questions. This diverse approach includes areas such as molecular biology, immunology, biostatistics, decision-making analysis, risk assessment, outcomes research and cost effectiveness studies. Host-pathogen and antimicrobial drug discovery studies utilize biostatistics to identify populations at risk and whole animal high-throughput screens, along with screening by imaging, to identify lead compounds, and study the common, fundamental set of molecular mechanisms that are employed by bacterial and fungal pathogens against a widely divergent array of metazoan hosts. Overall, their work has resulted in more than 325 peer-reviewed publications. Dr. Mylonakis has also edited eight books on infectious diseases.
The laboratory also studies the outcome of the interaction between a pathogen and a host. Some virulence factors are induced only in the host and may therefore require specialized techniques to be identified, based on detection of these genes in vivo or the survival of mutagenized strains within specific host environments. The Mylonakis lab developed invertebrate systems for the study of fungal pathogenesis. The hypothesis is that a common, fundamental set of molecular mechanisms is employed by fungal pathogens against a widely divergent array of metazoan hosts. These surrogate hosts fill an important niche in microbial pathogenesis research and, along with established mammalian models, provide a unique opportunity to identify and study basic, evolutionarily conserved aspects of microbial virulence and the host response. One approach uses Caenorhabditis elegans in a high-throughput, whole-animal assay to screen libraries of chemical compounds and identify those with antifungal activity. In vivo evaluation of chemical compound libraries solves some of the main obstacles in current antifungal discovery, such as finding new classes of compounds and reducing the bottleneck of toxicity/efficacy testing.
These investigations have identified novel virulence factors, cross kingdom pathogen-pathogen interactions, novel antimicrobial agents, and evolutionarily conserved traits that are involved in virulence and immune responses during infection. This approach challenges the position that studies in pathogenesis should focus on the analysis of the “host”, the “pathogen”, or the “antimicrobial compound”. Over the last decade, well over 80,000 compounds have been screened and a number of novel scaffolds have been identified. Collaborations have also been established that support a drug discovery program based on molecular and classical microbiology, biochemistry, medicinal chemistry, toxicology, pharmacokinetic testing in animals, and efficacy studies to drive the discovery of new antimicrobial compounds, their mechanisms of action, and mechanisms of resistance.
The Mylonakis laboratory also has a substantial effort in translational and clinical research. The group analyses big data develops cost-effective decision trees, and the advances new diagnostic and treatment strategies
Keywords: MRSA, clinical trial, antibiotic, drug discovery, C. elegans, Staphylococcus, pathogenesis, cost effectiveness, large data management, Candida, fungal pathogenesis, resistance
Discovery and Optimization of nTZDpa as an Antibiotic Effective Against Bacterial Persisters.
Kim W, Steele AD, Zhu W, Csatary EE, Fricke N, Dekarske MM, Jayamani E, Pan W, Kwon B, Sinitsa IF, Rosen JL, Conery AL, Fuchs BB, Vlahovska PM, Ausubel FM, Gao H, Wuest WM, Mylonakis E. ACS Infect Dis. 2018 Nov 9;4(11):1540-1545. doi: 10.1021/acsinfecdis.8b00161. Epub 2018 Aug 28.
A new class of synthetic retinoid antibiotics effective against bacterial persisters.
Kim W, Zhu W, Hendricks GL, Van Tyne D, Steele AD, Keohane CE, Fricke N, Conery AL, Shen S, Pan W, Lee K, Rajamuthiah R, Fuchs BB, Vlahovska PM, Wuest WM, Gilmore MS, Gao H, Ausubel FM, Mylonakis E. Nature. 2018 Apr 5;556(7699):103-107. doi: 10.1038/nature26157. Epub 2018 Mar 28.
An Intestine-Derived Neuropeptide Controls Avoidance Behavior in Caenorhabditis elegans.
Lee K, Mylonakis E. Cell Rep. 2017 Sep 5;20(10):2501-2512. doi: 10.1016/j.celrep.2017.08.053.
Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin-resistant Staphylococcus aureus.
Johnston T, Van Tyne D, Chen RF, Fawzi NL, Kwon B, Kelso MJ, Gilmore MS, Mylonakis E. Sci Rep. 2018 May 4;8(1):7062. doi: 10.1038/s41598-018-25571-w.
Repurposing the anthelmintic drug niclosamide to combat Helicobacter pylori.
Tharmalingam N, Port J, Castillo D, Mylonakis E. Sci Rep. 2018 Feb 27;8(1):3701. doi: 10.1038/s41598-018-22037-x.
The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship.
Pliakos EE, Andreatos N, Shehadeh F, Ziakas PD, Mylonakis E. Clin Microbiol Rev. 2018 May 30;31(3). pii: e00095-17. doi: 10.1128/CMR.00095-17. Print 2018 Jul. Review.
The impact of antibiotic prescription rates on the incidence of MRSA bloodstream infections: A county-level, US-wide analysis.
Andreatos N, Shehadeh F, Pliakos EE, Mylonakis E. Int J Antimicrob Agents. 2018 Aug;52(2):195-200. doi: 10.1016/j.ijantimicag.2018.04.003. Epub 2018 Apr 12.
The Attributable Burden of Clostridium difficile Infection to Long-Term Care Facilities Stay: A Clinical Study.
Karanika S, Grigoras C, Flokas ME, Alevizakos M, Kinamon T, Kojic EM, Mylonakis E.
J Am Geriatr Soc. 2017 Aug;65(8):1733-1740. doi: 10.1111/jgs.14863. Epub 2017 Mar 17.
T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial.
Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, Groeger JS, Judson MA, Vinagre YM, Heard SO, Zervou FN, Zacharioudakis IM, Kontoyiannis DP, Pappas PG. Clin Infect Dis. 2015 Mar 15;60(6):892-9. doi: 10.1093/cid/ciu959. Epub 2015 Jan 12.
Methicillin-resistant Staphylococcus aureus prevention strategies in the ICU: a clinical decision analysis*.
Ziakas PD, Zacharioudakis IM, Zervou FN, Mylonakis E. Crit Care Med. 2015 Feb;43(2):382-93. doi: 10.1097/CCM.0000000000000711.
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