Publication: Efecto de la terapia antimicrobiana frente a biofilms duales de Mycobacterium abscessus y Pseudomonas aeruginosa
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2021-07-19
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Universidad Complutense de Madrid
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Abstract
La enfermedad pulmonar crónica es la principal causa de morbilidad y mortalidad en pacientes con fibrosis quística (FQ). Las bacterias se establecen en los pulmones de los pacientes con FQ formando biofilms polimicrobianos, estructuras agregadas de microorganismos con una alta tolerancia frente al tratamiento antimicrobiano. Pseudomonas aeruginosa es la especie más prevalente en estos pacientes. Sin embargo, la microbiota del ecosistema pulmonar también puede estar compuesta por otros microorganismos, entre los que se encuentran las Micobacterias No Tuberculosas (MNT), que se adquieren mayoritariamente a partir de reservorios ambientales. Mycobacterium abscessus es un microorganismo que causa infección pulmonar en FQ cuya incidencia está aumentando globalmente. Algunos estudios sugieren que la terapia con antimicrobianos, a los que estos pacientes se exponen desde la infancia, podría favorecer la colonización pulmonar por M. abscessus dada su resistencia intrínseca a antibióticos. El tratamiento de la enfermedad pulmonar por M. abscessus se basa en la combinación de diferentes antimicrobianos, cuya elección está guiada por el antibiograma del aislado. Sin embargo, la tasa de fallo terapéutico y la recurrencia es alta, sugiriendo una falta de correlación in vitro-in vivo. En este trabajo tratamos de determinar si la incorporación de factores del microambiente del huésped, como células epiteliales de pulmón, y microorganismos con los que M. abscessus comparte nicho, como P. aeruginosa, pueden modificar la sensibilidad a antimicrobianos de M. abscessus. Además, también pretendemos evaluar si el tratamiento antimicrobiano frente a otros patógenos frecuentemente coaislados con M. abscessus, como P. aeruginosa, podría aumentar la supervivencia de M. abscessus en un biofilm dual...
Chronic lung infection is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. Bacteria in the CF lung are arranged as polymicrobial biofilms, which are aggregated structures of sessile microorganisms highly tolerant to antimicrobial therapy. Pseudomonas aeruginosa is the most prevalent species causing acute and chronic respiratory infection among CF patients. However, the CF lung microbiota also comprises other microorganisms, such as Non- Tuberculous Mycobacteria (NTM), which are presumed to be acquired from environmental reservoirs. Mycobacterium abscessus is a microorganism that can cause biofilm-related pulmonary infections in patients with preexisting lung disease and is increasingly being isolated from respiratory samples of CF patients. Some studies suggest that antimicrobial therapy, to which CF patients are exposed since childhood, may favor the colonization of the lung environment by M. abscessus, given its intrinsic resistance to antibiotics. The treatment against M. abscessus lung disease is based on a multidrug regimen guided by the in vitro susceptibility testing results of the isolates. However, the rates of therapeutic failure and recurrence are high, suggesting a poor correlation between the in vitro result and the in vivo outcome. This study aims to determine if the incorporation of factors that mimic the host microenvironment, such as lung epithelial cells, and microorganisms that share niche with M. abscessus, such as P. aeruginosa, can influence M. abscessus response to antimicrobial treatment. Furthermore, we aim to evaluate if the treatment directed at other classic pathogens often co-isolated with M. abscessus, like P. aeruginosa, could give an adaptive advantage to M. abscessus...
Chronic lung infection is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. Bacteria in the CF lung are arranged as polymicrobial biofilms, which are aggregated structures of sessile microorganisms highly tolerant to antimicrobial therapy. Pseudomonas aeruginosa is the most prevalent species causing acute and chronic respiratory infection among CF patients. However, the CF lung microbiota also comprises other microorganisms, such as Non- Tuberculous Mycobacteria (NTM), which are presumed to be acquired from environmental reservoirs. Mycobacterium abscessus is a microorganism that can cause biofilm-related pulmonary infections in patients with preexisting lung disease and is increasingly being isolated from respiratory samples of CF patients. Some studies suggest that antimicrobial therapy, to which CF patients are exposed since childhood, may favor the colonization of the lung environment by M. abscessus, given its intrinsic resistance to antibiotics. The treatment against M. abscessus lung disease is based on a multidrug regimen guided by the in vitro susceptibility testing results of the isolates. However, the rates of therapeutic failure and recurrence are high, suggesting a poor correlation between the in vitro result and the in vivo outcome. This study aims to determine if the incorporation of factors that mimic the host microenvironment, such as lung epithelial cells, and microorganisms that share niche with M. abscessus, such as P. aeruginosa, can influence M. abscessus response to antimicrobial treatment. Furthermore, we aim to evaluate if the treatment directed at other classic pathogens often co-isolated with M. abscessus, like P. aeruginosa, could give an adaptive advantage to M. abscessus...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 24/02/2021