Group photo. Jesus Gonzalo-Asensio
Current situation of tuberculosis
Tuberculosis (TB) has been the deadliest infectious disease throughout history, and today it still is, claiming 1.6 million lives. In addition, 1.7 billion people, a quarter of the world's population, are latently infected and are at risk of reactivation at any time in life. Even more alarming is the emergence of strains resistant to the already rare anti-TB drugs, making treatment difficult or even impossible. To this fact must be added the difficulty in finding new drugs and the relative ease with which tuberculosis bacteria develop resistance to them. The TB epidemic continues despite the existence of a vaccine, called BCG. This is due to the efficacy of BCG in preventing pulmonary tuberculosis in children, but its gradual loss of efficacy in adolescents and adults (WHO 2018).
Team “New vaccines against tuberculosis” PI: Carlos Martín
Team “New vaccines against tuberculosis” PI: Carlos MartínTeam “New vaccines against tuberculosis” PI: Carlos MartínTeam “New vaccines against tuberculosis” PI: Carlos Martín et al. 2015), MTBVAC has also been shown to be a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country like South Africa (Phase1b) (Tameris et al. 2015), MTBVAC has also been shown to be a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country like South Africa (Phase1b) (Tameris
2015), MTBVAC has also been shown to be a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country like South Africa (Phase1b) (Tameris
2015), MTBVAC has also been shown to be a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country like South Africa (Phase1b) (Tameris
2015), MTBVAC has also been shown to be a safe and more immunogenic vaccine than BCG in newborns in a TB endemic country like South Africa (Phase1b) (Tameris Team “New vaccines against tuberculosis” PI: Carlos Martín (MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ((MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ((MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB (Team “New vaccines against tuberculosis” PI: Carlos Martín(MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ( et al(MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ((MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ( (MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ( et al. 2018). Both findings have allowed us to decipher the molecular bases of the adaptation of a strange strain of (MTBC). MTBC comprises 8 lineages with homology greater than 99.95% at the genomic level. This, coupled with the absence of “classical” virulence factors or the lack of horizontal gene transfer events, makes understanding host-pathogen adaptation mechanisms challenging. Our team has deciphered how a polymorphism in the PhoPR virulence system causes its loss of functionality in the bacterium that causes bovine TB ( . 2018). Both findings have allowed us to decipher the molecular bases of the adaptation of a strange strain of
. 2018). Both findings have allowed us to decipher the molecular bases of the adaptation of a strange strain of
Team D2AMR: . 2018). Both findings have allowed us to decipher the molecular bases of the adaptation of a strange strain of
. 2018). Both findings have allowed us to decipher the molecular bases of the adaptation of a strange strain of2AMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara et alAMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara et alAMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara
Our investigations are mainly focused on Team “New vaccines against tuberculosis” PI: Carlos MartínAMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara AMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (GómaraAMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara Staphylococcus aureus, Streptococcus pneumoniae, AMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara AMR include the characterization of mechanisms of intrinsic resistance to antimicrobials, discovery and pre-clinical development of bioactive compounds as new antimicrobials, repositioning of drugs with antimicrobial applications based on synergism, nanoparticles as vehicles for antimicrobial drugs and the development of pharmacological models. dynamic for the study of the activity of antimicrobials (Gómara
The team is completed by Ainhoa Lucía, Begoña Gracia, Ernesto Anoz, Lara Muñoz, Ana Cristina Millán, Marta Gómara, José Manuel Ezquerra, and Mª Pilar Arenaz.
The team is completed by Ainhoa Lucía, Begoña Gracia, Ernesto Anoz, Lara Muñoz, Ana Cristina Millán, Marta Gómara, José Manuel Ezquerra, and Mª Pilar Arenaz.
In addition to the development of new tuberculosis vaccines, there is interest in the field in studying new inoculation routes to make existing vaccines more effective. In this sense, the pulmonary inoculation route has been shown in different animal models to be more effective than the intradermal route, which is currently used with BCG. The fact that vaccination mimics the tuberculosis infection pathway causes different immune mechanisms to be stimulated in the lungs at a local level that efficiently stop the infection. Our group has studied in mouse models the use of live attenuated vaccines, such as BCG or MTBVAC, administered intranasally, observing that this route of administration stimulates a local immune response in the lungs that is not obtained when mice are vaccinated intranasally. intradermal, highlighting the role of IL17 and secretory immunoglobulins (Aguilo et al. 2014; Aguilo et al . 2014; Aguilo
. 2014; Aguilo
. 2014; Aguilo
Through molecular studies we are able to differentiate the different MTBC strains (genomic typing), classify them into different lineages and analyze their evolution. This has numerous applications such as outbreak studies, differentiating recent transmission from reactivation, population studies, and epidemiological surveillance. With the ultimate goal of reducing the incidence rate of TB, we collaborate with the health authorities typifying the strains isolated in Aragon and coordinate the network "Spanish Working Group on Multi-resistant Tuberculosis", aimed at detecting the possible spread of multi-resistant in Spain in collaboration with the European Union. Those strains that present greater transmissibility, that remain in a state of latency and reactivate, and those that present resistance are the object of a detailed study (Pérez-Lago et al. 2019). Using transposition mutagenesis to detect genes involved in latency, we have been able to isolate a mutant with new phenotypic characteristics and differentially expressed in stationary phase and growing in cholesterol as the sole carbon source (Otal et al. 2017).
The team is completed by Jessica Comín, María José Iglesias and Daniel Ibarz.
References
Aguilar-Pérez, C., B. Gracia, L. Rodrigues, A. Vitoria, R. Cebrián, N. Deboosère, O.R. Song, P. Brodin, M. Maqueda, and J.A. Aínsa. (2018) “Synergy between circular bacteriocin AS-48 and ethambutol against Mycobacterium tuberculosis“. Antimicrob Agents Chemother. 62(9): e00359-18.
Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “ Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “
Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “ “Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “ Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “
Aguilo N, A.M. Toledo, E.M. Lopez-Roman, E. Perez-Herran, E. Gormley, J. Rullas-Trincado, I. Angulo-Barturen, and C. Martin (2014). “ in vitro synergy screens at their inception”. Biochem Pharmacol. 163:299-307.
synergy screens at their inception”. Biochem Pharmacol. 163:299-307. “synergy screens at their inception”. Biochem Pharmacol. 163:299-307.” synergy screens at their inception”. Biochem Pharmacol. 163:299-307.
synergy screens at their inception”. Biochem Pharmacol. 163:299-307. “synergy screens at their inception”. Biochem Pharmacol. 163:299-307.” synergy screens at their inception”. Biochem Pharmacol. 163:299-307.
Otal I., E. Pérez-Herrán, L. Garcia-Morales, M.C. Menéndez, J.A. Gonzalez-Y-Merchand, C. Martín and M.J. García (2017). “Detection of a Putative TetR-Like Gene Related to Mycobacterium bovis BCG Growth in Cholesterol Using a gfp-Transposon Mutagenesis System”. Front Microbiol. Mar 6;8:315.
Pérez-Lago, L., M.I. Campos-Herrero, F. Cañas, R. Copado, L. Sante, B. Pino, M. Lecuona, O.D. Gil, C. Martín, P. Muñoz, D. García-de-Viedma and S. Samper (2019). "TO Mycobacterium tuberculosis Beijing strain persists at high rates and extends its geographic boundaries 20 years after importation”. Sci Rep. Mar 18;9(1):4687.
Spertini, F., R. Audran, R. Chakour, O. Karoui, V. Steiner-Monard, A. C. Thierry, C. E. Mayor, N. Rettby, K. Jaton, L. Vallotton, C. Lazor-Blanchet, J. Doce, E. Puentes, D. Marinova, N. Aguilo and C. Martin (2015). “Spertini, F., R. Audran, R. Chakour, O. Karoui, V. Steiner-Monard, A. C. Thierry, C. E. Mayor, N. Rettby, K. Jaton, L. Vallotton, C. Lazor-Blanchet, J. Doce, E. Puentes, D. Marinova, N. Aguilo and C. Martin (2015).” Spertini, F., R. Audran, R. Chakour, O. Karoui, V. Steiner-Monard, A. C. Thierry, C. E. Mayor, N. Rettby, K. Jaton, L. Vallotton, C. Lazor-Blanchet, J. Doce, E. Puentes, D. Marinova, N. Aguilo and C. Martin (2015).
Spertini, F., R. Audran, R. Chakour, O. Karoui, V. Steiner-Monard, A. C. Thierry, C. E. Mayor, N. Rettby, K. Jaton, L. Vallotton, C. Lazor-Blanchet, J. Doce, E. Puentes, D. Marinova, N. Aguilo and C. Martin (2015). “Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial.” Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial.
Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial. “Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial.”