We protect your health through science
Investigation
Water-borne and Food-borne Bacterial Diseases
Research Lines
Content with Investigacion .
The prophylactic and empirical use of antifungal agents in general, and azoles and echinocandins in particular, has contributed to the emergence of strains with elevated MICs (microbiological resistance), whose clinical impact and relevance are increasingly concerning. Moreover, therapeutic failure or clinical resistance is frequently observed even in the absence of microbiological resistance.
One of the factors that may explain clinical resistance in the absence of microbiological resistance is inadequate drug exposure at the site of infection, together with the pathogen’s adaptive response to host defences or to the administered antifungal therapy.
This research line, active since 2010, aims to advance the understanding of clinical resistance in Aspergillus fumigatus infection through the study of antifungal dose–response relationships by evaluating PK/PD parameters and their role in treatment efficacy. In addition, it investigates the role of biofilms as adaptive strategies that enhance fungal resistance to antifungal agents and to host immune cells.
Exposure: Pharmacokinetics of Antifungal Agents
There is now substantial evidence that the administration of an effective antifungal agent at the appropriate dose is essential to achieve adequate drug concentrations at the site of infection. Through the development of this research line (active since 2009), our group has gained extensive expertise in the development and application of chromatographic methods (HPLC/UPLC–UV/fluorescence) for antifungal quantification, which are useful for therapeutic drug monitoring (TDM).
Techniques that allow monitoring of blood drug concentrations constitute essential tools in patient management, enabling dose optimization by determining whether drug exposure is inadequate—potentially contributing to therapeutic failure and the emergence of resistance—or, conversely, excessive, thereby increasing the risk of significant toxicity.
In addition, the application of disciplines such as pharmacogenetics to antifungal therapy is promoting personalized treatment approaches and improving the management of severe invasive fungal infections (IFIs).
The use of alternative animal models, with ethical approval and under regulatory frameworks, together with methodological advances, has facilitated the preliminary study of dose–response relationships for both established antifungal agents and newly developed compounds.
Response: Monitoring Treatment Efficacy
An aspect of major relevance in the management of severe invasive fungal infections (IFIs) is the evaluation of the efficacy of the administered therapy. This research line further explores the characterization of circulating fungal-specific biomarkers that may help distinguish infection from fungal colonization and assess the effectiveness of the established treatment.
Within this framework, our efforts have focused on the study and characterization of compounds related to fungal secondary metabolism, such as gliotoxin and its derivative bis(methylthio)gliotoxin, detected in tissue and blood samples from patients with aspergillosis and in animal models, as well as other metabolites associated with fungal virulence (e.g., fumagillin and pseurotin A).
More recently, this research line has expanded to investigate adaptive strategies such as the formation of complex biofilm structures—often multispecies in nature and involving intricate interaction mechanisms—which may explain fungal resistance to antifungal agents and host immune cells, thereby contributing to therapeutic failure (clinical resistance).
Research projects
Content with Investigacion .
Funded Research Projects (Competitive Public Calls)
Projects as Principal Investigator
1.Title: Proteomic Analysis of Fungal Biofilms (Mono- and Multispecies): Importance of the Extracellular Matrix
Funding Agency: AESi 2025 (Grant No. PI25/00038)
Funding Amount: €117,500
Duration: 2026–2028
Principal Investigator: Alicia Gómez-López
2. Title: Study of Biomarkers Involved in the Development and Evolution of Fungal Biofilms
Funding Agency: AESi 2021 (Grant No. PI21CIII/00012; MPY 435/21)
Funding Amount: €40,450
Duration: 2022–2024 (extended to 2025)
Principal Investigator: Alicia Gómez-López
3. Title: Novel Strategies for Characterizing Progression and Response to Fungal Infection: Application of Advanced Chromatographic Techniques
Funding Agency: AESi FIS (Grant No. PI16CIII/00014; MPY 1347/16)
Funding Amount: €41,500
Duration: 2017–2021
Principal Investigator: Alicia Gómez-López
4. Title: Management and Maintenance of the Yeast and Filamentous Fungi Strain Collection of the National Reference Mycology Laboratory (CNM-ISCIII)
Project Reference: PEJ-2014-A-13436
Scientific Area: Technology Transfer
Duration: 2016–2018
Principal Investigator / Supervisor: Alicia Gómez-López
5. Title: Genetic Variants of Drug-Metabolizing Enzymes (CYP450) and Voriconazole Monitoring in Treated Patients: Implications for Clinical Decision-Making
Funding Agency: AES FIS 2013 (Grant No. PI13/01817; MPY 1367/13)
Funding Amount: €86,515
Duration: 2013–2016
Role: Principal Investigator
6. Title: Clinical Relevance of Azole Resistance in an Animal Model of Invasive Aspergillosis: Characterization of PK/PD Parameters
Funding Agency: ISCIII Emerging Groups Program (MPY 1354/10)
Funding Amount: €63,613 (Technical Contract – FP)
Duration: 2010–2012
Role: Principal Investigator
7. Title: Clinical Relevance of Azole Resistance in an Animal Model of Invasive Aspergillosis: Characterization of PK/PD Parameters
Funding Agency: AES FIS (Grant No. PI09/0624; MPY 1003/10)
Funding Amount: €50,820
Duration: 2010–2012
Role: Principal Investigator
Collaborating Researcher
Title: Pilot Project for the Development of a Molecular Surveillance Network for Antifungal Resistance Integrating Microbiological and Clinical Data (FunResNet)
Consortium: Biomedical Research Networking Center (CIBERINFEC), Infectious Diseases Area
Funding Agency: CIF: G85296226 (Grant No. IM23/INFEC/2)
Duration: 2024–2025
Principal Investigator: Ana Alastruey-Izquierdo
Collaborating Researcher: Alicia Gómez-López
Title: Biomarkers in Bronchoalveolar Lavage for the Diagnosis and Prognostic Assessment of Invasive Pulmonary Aspergillosis
Consortium: Biomedical Research Networking Center (CIBERINFEC), Infectious Diseases Area
Funding Agency: CIF: G85296226 (Grant No. IM23/INFEC/7)
Funding Amount: €63,000
Duration: 2024–2025
Principal Investigator: Laura Alcázar-Fuoli
Collaborating Researcher: Alicia Gómez-López
Title: Biomedical Research Networking Center (CIBER), Infectious Diseases Area
Funding Agency: CIF: G85296226 (Grant No. CB21/13/00105)
Funding Amount: €85,000 (first year)
Duration: 2022–2026
Role: Technological Development – Collaborating Researcher
Principal Investigator: Emilia Mellado-Terrado
Industry-Funded Research Projects
Title: Rezafungin: An Attempt to Optimize In Vitro Susceptibility Against a Collection of Clinical Yeasts
Funding Company/Institution: Mundipharma Research / Micología Molecular S.L.
Duration: 2025
Principal Investigator: Alicia Gómez-López
Title: Determination of Benznidazole Concentrations in Serum and Urine of Treated Rabbits
Funding Company/Institution: Micología Molecular S.L. / Fundación MundoSano
Duration: 2024
Principal Investigator: Javier Nieto
Role: Technological Development – Collaborating Researcher
Researcher: Alicia Gómez-López (Madrid, Spain)
Title: Phase IV, Single-Center, Multiple-Dose, Single-Arm Clinical Trial to Assess the Bronchopulmonary Penetration of Isavuconazole in Lung Transplant Recipients (EudraCT No. 2019-004240-30)
Duration: 2020–2021
Role: Collaborating Researcher
Principal Investigators: Piedad Ussetti-Gil; Belén Ruiz-Antorán (Hospital Puerta de Hierro, Madrid)
Title: Prospective, Randomized Pilot Study on the Feasibility of Nebulized Liposomal Amphotericin B (nL-AmB) as Adjunctive Therapy for Invasive Pulmonary Aspergillosis
Funding Company: Micología Molecular S.L.
Duration: 2019–2021
Principal Investigator: Jesús Fortún-Abete
Role: Collaborating Researcher
Title: Sequential Plasma Pharmacokinetic Study of Two Oral Posaconazole Formulations (Oral Suspension and Gastro-Resistant Tablets) in Hematology Patients at High Risk of Invasive Fungal Infections (Protocol Code POPK-1501)
Funding Company/Institution: MSD / Micología Molecular S.L.
Duration: 2017
Role: Collaborating Researcher
Title: Validation of Real-Time PCR in Blood and Peritoneal Fluid for the Diagnosis of Candida Peritonitis. Peritoneal Pharmacokinetics and Echinocandin Resistance Analysis
Duration: 2016–2018
Funding Company: Micología Molecular S.L.
Role: Collaborating Researcher
Title: In Vitro Activity of Cyanobacterial Extracts Against a Collection of Yeast and Filamentous Fungi
Duration: 2013
Funding Institution: Valoralia I+D+i
Role: Principal Investigator
Title: Arasertaconazole Nitrate: In Vitro Activity Against Candida spp. by Time–Kill Studies
Duration: 2010–2011
Funding Company: Grupo Ferrer
Role: Principal Investigator
Title: Arasertaconazole Nitrate: In Vitro Susceptibility Study Against Clinical Isolates of Candida
Duration: 2010–2011
Funding Company: Grupo Ferrer
Role: Principal Investigator
Publications
Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation.
Espigado I, de la Cruz-Vicente F, BenMarzouk-Hidalgo OJ, Gracia-Ahufinger I, Garcia-Lozano JR, Aguilar-Guisado M, Cisneros JM, Urbano-Ispizua A, Perez-Romero P*. Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation. Transpl Int. 2014 Dec;27(12):1253-62.
PUBMED DOIClinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients.
Martín-Gandul C, Pérez-Romero P*, González-Roncero FM, Berdaguer S, Gómez MA, Lage E, Sánchez M, Cisneros JM, Cordero E; Spanish Network for Research in Infectious Diseases REIPI. Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. J Infect. 2014 Nov;69(5):500-6.
PUBMED DOIViral load, CMV-specific T-cell immune response and cytomegalovirus disease in solid organ transplant recipients at higher risk for cytomegalovirus infection during preemptive therapy.
Martín-Gandul C, Pérez-Romero P*, Blanco-Lobo P, Benmarzouk-Hidalgo OJ, Sánchez M, Gentil MA, Bernal C, Sobrino JM, Rodríguez-Hernández MJ, Cordero E; Spanish Network for Research in Infectious Diseases (REIPI). Viral load, CMV-specific T-cell immune response and cytomegalovirus disease in solid organ transplant recipients at higher risk for cytomegalovirus infection during preemptive therapy. Transpl Int. 2014 Oct;27(10):1060-8.
PUBMED DOIContent with Investigacion .
-
Alicia Gómez López
Research Scientist
ORCID code: 0000-0003-2780-5039
Doctor of Pharmacy from the Complutense University of Madrid and specialist in Microbiology and Parasitology via FIR (La Paz Hospital, Madrid). He completed his doctoral thesis at the Reference and Research Laboratory in Mycology under the supervision of Manuel Cuenca-Estrella. Currently a career civil servant in the Scientific Scale of O.P.I. at the Reference and Research Laboratory in Mycology.
Since 2010, he has been leading a line of research that seeks to advance clinical resistance in fungal infection through the study of dose/response relationships, the evaluation of PK/PD parameters of antifungals and their role in efficacy, as well as the study of biofilms as strategies that favour the resistance of fungal cells to the action of antifungals and immune cells. This line of research has resulted in the development and application of chromatographic methods (UPLC-UV) for antifungal monitoring and the characterisation of fungal biomolecules indicative of infection progression, which are useful for evaluating treatment response and diagnosis. Some of these methodologies have been validated according to protocols defined by the EMA and have been recognised by ENAC as valid methods for monitoring azoles in clinical samples. They are currently part of LRIM's portfolio of services and are in high demand as this methodology is not always available in clinical laboratories.
This line of research has been active since 2009, with continuous funding through various competitive calls from the AES as well as other collaborative private funding projects (9 Research Projects as IP in the period 2010-2025, Strategic Action in Health, AES FIS-ISCIII, calls for proposals 2009, 2013, 2016, 2021 and 2025; 22 research projects leading/collaborating in experimental or technological developments in the period 2000-2025).
-
Beatriz Bellido Samaniego
Senior Technician Facultative Specialist
Ms. Bellido-Samaniego holds a Degree in Pharmacy from the Complutense University of Madrid (1995) and a Master’s Degree in Microbiology and Parasitology (Complutense University of Madrid, 2016). She joined the Mycology Reference and Research Laboratory (LRIM) in January 2024. She has developed a broad multidisciplinary professional career within the field of microbiology. Since 1997, she has been affiliated with the Carlos III Health Institute (ISCIII), initially as a Research Trainee (1997–2000) and subsequently as Head of the Legionella Laboratory at the National Microbiology Center (2000–2023), where she carried out national reference activities.
She currently serves as Quality Management System Coordinator at the Mycology Reference and Research Laboratory, overseeing accredited reference analyses under ENAC standards. She has co-authored one scientific publication and one book chapter and has participated in three national and international scientific conferences. -
Leticia Bernal Martínez
Staff Scientist
ORCID code: 0000-0002-1694-5522
Dr. Bernal-Martínez obtained her degree in Biochemistry from the University of Zaragoza in 2005. She joined the Mycology Reference and Research Laboratory (LRIM) in 2006 under a trainee contract and completed her PhD within the Official Doctoral Program in Microbiology and Parasitology at the Complutense University of Madrid, defending her thesis in 2010 with highest honors (Cum Laude). In 2007, she continued her research activity at LRIM within the framework of the Spanish Network for Research in Infectious Diseases (REIPI). In 2016, she completed a Postgraduate Diploma in Promotion and Management of International Projects (Technical University of Madrid) and undertook a research stay at the Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho (Braga, Portugal). She was subsequently appointed as a PhD researcher within the Biomedical Research Networking Center in Infectious Diseases (CIBERINFEC). Since 2024, she serves as Specialist Scientist at the Carlos III Health Institute (ISCIII) and is responsible for the Diagnostic and Serology Section for Endemic Fungi at the Mycology Reference and Research Laboratory.
Dr. Bernal-Martínez has authored more than 30 peer-reviewed scientific publications and two book chapters. She has actively participated in over 12 research projects and has presented her work at numerous national and international scientific conferences. Her research has focused on human fungal infections, antifungal resistance, therapeutic drug monitoring, genetic variants associated with antifungal metabolism, and the identification of predictive biomarkers of invasive fungal infections. However, her primary expertise lies in the diagnostic field, particularly in the design, optimization, and validation of real-time PCR–based methodologies.
She is currently Principal Investigator of a research project aimed at improving current diagnostic techniques for invasive fungal infections, evaluating emerging diagnostic technologies, and studying primary fungal pathogens. A substantial part of her work has been transferred to the Spanish National Health System and to research centers in Latin America. Many of the diagnostic methodologies developed have been incorporated into the official service portfolio of ISCIII. She has collaborated with multiple hospitals through research projects and clinical trials applying these technologies, as well as with the ISCIII spin-off company Micomol S.L.
Dr. Bernal-Martínez has supervised several Master’s and Undergraduate Final Degree Projects from students at the Complutense University of Madrid and the University of Alcalá. She is a member of the teaching staff of the UNED-ISCIII PhD Program in Biomedical Sciences and Public Health and serves as lecturer in the Master’s Program in Public Health and Research in Infectious Diseases at the University of Alcalá.
List of staff
Additional Information
The Reference and Research Laboratory for Water-borne an Food-borne Bacterial Diseases (LRIEBTAA) is recognized as a national reference laboratory for the zoonotic agents Salmonella, verotoxigenic Escherichia coli, Yersinia., Campylobacter. and Vibrio (RD 1940/2004 of September 27, Order APA/1808/2007 of June 13). In this sense, its main activity is to ensure adequate surveillance of these zoonoses, zoonotic agents and associated antibiotic resistance, as well as proper investigation of outbreaks caused by these microorganisms. In addition, the LRIEBTAA acts as a reference laboratory for Shigella, other diarrheagenic groups of E. coli, Legionella and toxigenic Corynebacterium species. Added to its reference activity is its applied research activity, among which those mentioned above stand out.
The members of the group carry out an important training activity. Every year, 3-5 students who develop their final Master's or Degree projects, laboratory technicians in training and rotating students of the specialty of Clinical Microbiology from different national origins are welcomed in the laboratory. In addition, it actively participates in the Public Health microbiologist training program funded by the ECDC through its supervision at the national level and coordination/supervision at the international level.
The Reference and Research Laboratory for Water-borne an Food-borne Bacterial Diseases (LRIEBTAA) is recognized as a national reference laboratory for the zoonotic agents Salmonella, verotoxigenic Escherichia coli, Yersinia., Campylobacter. and Vibrio (RD 1940/2004 of September 27, Order APA/1808/2007 of June 13). In this sense, its main activity is to ensure adequate surveillance of these zoonoses, zoonotic agents and associated antibiotic resistance, as well as proper investigation of outbreaks caused by these microorganisms. In addition, the LRIEBTAA acts as a reference laboratory for Shigella, other diarrheagenic groups of E. coli, Legionella and toxigenic Corynebacterium species. Added to its reference activity is its applied research activity, among which those mentioned above stand out.
The members of the group carry out an important training activity. Every year, 3-5 students who develop their final Master's or Degree projects, laboratory technicians in training and rotating students of the specialty of Clinical Microbiology from different national origins are welcomed in the laboratory. In addition, it actively participates in the Public Health microbiologist training program funded by the ECDC through its supervision at the national level and coordination/supervision at the international level.