Institute of Molecular Biology

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Loading profile for Melanie Spero

Research Interests

Bacteria have the remarkable ability to adapt to a huge range of environments. In the Spero lab, we are interested in how bacterial pathogens grow and survive within host environments during chronic infections, such as those found in the lungs of patients with cystic fibrosis or in patients with chronic wounds. We are interested in the following types of questions:

We know some of the answers to some of these questions. For instance, many host environments have low oxygen tensions, and conventional antibiotics often fail to kill bacteria under anoxic conditions. This has profound effects on human health outcomes, and likely explains why aggressive antibiotic treatment regimens fail to resolve chronic infections. We previously showed that the antibiotic, tobramycin, fails to kill hypoxic/anoxic populations of Pseudomonas aeruginosa biofilms. However, a promising new pro-drug, chlorate, very effectively kills hypoxic/anoxic populations by targeting cells that use a form of anaerobic metabolism called nitrate respiration (Spero and Newman, 2018).


At our core, we are a bacterial physiology lab seeking to clarify the relationship between the varied metabolic states adopted by pathogens like P. aeruginosa and their effects on important phenotypic outcomes like bacterial survival and drug susceptibility. For more information please visit our lab website:

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

Thermodynamic system drift in protein evolution.
Hart KM, Harms MJ, Schmidt BH, Elya C, Thornton JW, Marqusee S
PLoS Biol 2014 Nov;12(11):e1001994
Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors.
Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JW
Proc Natl Acad Sci U S A 2013 Jul 9;110(28):11475-80
Evolution of minimal specificity and promiscuity in steroid hormone receptors.
Eick GN, Colucci JK, Harms MJ, Ortlund EA, Thornton JW
PLoS Genet 2012;8(11):e1003072
Arginine residues at internal positions in a protein are always charged.
Harms MJ, Schlessman JL, Sue GR, García-Moreno B
Proc Natl Acad Sci U S A 2011 Nov 22;108(47):18954-9
Analyzing protein structure and function using ancestral gene reconstruction.
Harms MJ, Thornton JW
Curr Opin Struct Biol 2010 Jun;20(3):360-6
Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor.
Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW
PLoS Biol 2010 Oct 5;8(10)
The pK(a) values of acidic and basic residues buried at the same internal location in a protein are governed by different factors.
Harms MJ, Castañeda CA, Schlessman JL, Sue GR, Isom DG, Cannon BR, García-Moreno E B
J Mol Biol 2009 May 29;389(1):34-47
A buried lysine that titrates with a normal pKa: role of conformational flexibility at the protein-water interface as a determinant of pKa values.
Harms MJ, Schlessman JL, Chimenti MS, Sue GR, Damjanović A, García-Moreno B
Protein Sci 2008 May;17(5):833-45
Laser light-scattering evidence for an altered association of beta B1-crystallin deamidated in the connecting peptide.
Harms MJ, Wilmarth PA, Kapfer DM, Steel EA, David LL, Bächinger HP, Lampi KJ
Protein Sci 2004 Mar;13(3):678-86