Ecology and evolution of antibiotic resistance



José Luis Martínez

Group Leader



Research summary

Several infections at hospitals are due to opportunistic pathogens, microorganisms that rarely infect healthy people, but are a frequent cause of infection in people with basal diseases, who are immunodepressed or debilitated. Environmental bacteria, frequently antibiotic resistant, constitute a large percentage of those pathogens. Our work focuses on understanding the mechanisms of virulence and resistance, as well as possible crosstalk, of these pathogens.




Olivares Pacheco J, Alvarez-Ortega C, Alcalde Rico M, Martínez JL. Metabolic Compensation of Fitness Costs Is a General Outcome for Antibiotic-Resistant Pseudomonas aeruginosa Mutants Overexpressing Efflux Pumps. MBio. 2017 Jul 25;8(4). pii: e00500-17.

Martínez JL, Coque T, Baquero F. What is a Resistance Gene? Ranking Risks on Resistomes. Nat Rev Microbiol 2015; 13: 116-23

Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F, Bürgmann H, Sørum H, Norström M, Pons MN, Kreuzinger N, Huovinen P, Stefani S, Schwartz T, Kisand V, Baquero F, Martinez JL. Tackling antibiotic resistance: the environmental framework. Nat Rev Microbiol 2015; 13: 310-317

Reales-Calderón JA, Corona F, Monteoliva L, Gil C, Martínez JL. Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa. J Proteomics 2015; 127: 352-364

Bernardini A, Corona F, Dias R, Sánchez MB, Martínez JL. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response. Front Microbiol 2015; 6: 1068

More Publications


We study the biology of opportunistic pathogens, focusing on the networks and the evolutionary processes that connect resistance and virulence. In particular, in the last two years:

  1. We proposed that bacterial metabolism and antibiotic resistance are closely interlinked, and have explored the contribution of two global regulators of antibiotic resistance and virulence: the post-transcriptional regulator of carbon metabolism from Pseudomonas aeruginosa (Crc), and the RNAse G from Stenotrophomonas maltophilia. Our results support the idea that intrinsic resistance to antibiotics is not merely an adaptive response to presence of the antimicrobial, but an emergent property linked to the bacterial metabolic activity needed to maintain cell homeostasis.
  2. We proposed several rules for predicting the emergence of antibiotic resistance and are currently standardizing these tools, which are based on experimental evolution, whole-genome sequencing and functional assays. Using this approach, we characterized mechanisms of resistance to latest-generation antibiotics and identified the target and the mechanisms of resistance to antibiotics still being developed.
  3. We are currently studying the epigenetic events leading to transient resistance, in particular the signals that trigger such resistance, as well as identification of the deterministic (mainly populational) and stochastic aspects (at the single cell level) of antibiotic resistance.
  4. Microbial signalling is a complex situation with at least two levels of complexity. Some systems, such as the stringent response, operate mainly at the single cell level because the signal is not exported, whereas others such as the quorum sensing response, in which the signal is exported, operate at the population level. We aim to analyse the hierarchical integration of these signalling networks and study how acquisition of antibiotic resistance affects bacterial signalling, both at the single cell and at the population level.





José Luis Martínez Principal investigator
Blanca Sánchez Postdoctoral scientist
Sara Hernando-Amado Postdoctoral scientist
Aida Pitarch Postdoctoral scientist
Felipe Lira Predoctoral scientist
Manuel Alcalde Predoctoral scientist
Fernando Corona Predoctoral scientist
Paula Blanco Predoctoral student
Fernando Sanz-García Predoctoral student
Trinidad Cuesta Technicians

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