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Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability in Mtb.
View Article and Find Full Text PDFThe complexities of elexacaftor/tezacaftor/ivacaftor therapeutic drug monitoring in a person with cystic fibrosis and pulmonary disease.
Eur Clin Respir J
January 2025
Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, Queensland, Australia.
Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor.
View Article and Find Full Text PDFFitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection.
Sci Rep
January 2025
Experimental Pathology Department, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico.
It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4.
View Article and Find Full Text PDFUnveiling the critical roles of cellular metabolism suppression in antibiotic tolerance.
NPJ Antimicrob Resist
June 2024
William Brookshire Chemical and Biomolecular Engineering Department, University of Houston, Houston, TX, USA.
Metabolic inhibitors are known to exhibit complex interactions with antibiotics in bacteria, potentially acting as antagonists by inducing cell dormancy and promoting cell survival. However, the specific synergistic or antagonistic effects of these inhibitors depend on factors like their mechanisms of action, concentrations, and treatment timings, which require further investigation. In our study, we systematically explored the synergistic interactions of various metabolic inhibitors-such as chloramphenicol (a translation inhibitor), rifampicin (a transcription inhibitor), arsenate (an ATP production inhibitor), and thioridazine (a PMF inhibitor)-in combination with ofloxacin.
View Article and Find Full Text PDFAdvanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening.
J Tissue Eng
January 2025
Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
The development of advanced models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process.
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