Matches in SemOpenAlex for { <https://semopenalex.org/work/W4323364275> ?p ?o ?g. }
- W4323364275 abstract "ABSTRACT Transcriptome evaluation of Mycobacterium tuberculosis in the lungs of laboratory animals during long-term treatment has been limited by extremely low abundance of bacterial mRNA relative to eukaryotic RNA. Here we report a targeted amplification RNA sequencing method called SEARCH-TB. After confirming that SEARCH-TB recapitulates conventional RNA-seq in vitro , we applied SEARCH-TB to Mycobacterium tuberculosis- infected BALB/c mice treated for up to 28 days with the global standard isoniazid, rifampin, pyrazinamide, and ethambutol regimen. We compared results in mice with 8-day exposure to the same regimen in vitro . After treatment of mice for 28 days, SEARCH-TB suggested broad suppression of genes associated with bacterial growth, transcription, translation, synthesis of rRNA proteins and immunogenic secretory peptides. Adaptation of drug-stressed Mycobacterium tuberculosis appeared to include a metabolic transition from ATP-maximizing respiration towards lower-efficiency pathways, modification and recycling of cell wall components, large-scale regulatory reprogramming, and reconfiguration of efflux pumps expression. Despite markedly different expression at pre-treatment baseline, murine and in vitro samples had broadly similar transcriptional change during treatment. The differences observed likely indicate the importance of immunity and pharmacokinetics in the mouse. By elucidating the long-term effect of tuberculosis treatment on bacterial cellular processes in vivo , SEARCH-TB represents a highly granular pharmacodynamic monitoring tool with potential to enhance evaluation of new regimens and thereby accelerate progress towards a new generation of more effective tuberculosis treatment." @default.
- W4323364275 created "2023-03-08" @default.
- W4323364275 creator A5004253411 @default.
- W4323364275 creator A5004886856 @default.
- W4323364275 creator A5006152790 @default.
- W4323364275 creator A5008442458 @default.
- W4323364275 creator A5020602503 @default.
- W4323364275 creator A5022734861 @default.
- W4323364275 creator A5023085990 @default.
- W4323364275 creator A5031438280 @default.
- W4323364275 creator A5036646183 @default.
- W4323364275 creator A5037368174 @default.
- W4323364275 creator A5049438472 @default.
- W4323364275 creator A5052447524 @default.
- W4323364275 creator A5056039332 @default.
- W4323364275 creator A5064289739 @default.
- W4323364275 creator A5064493229 @default.
- W4323364275 creator A5064926798 @default.
- W4323364275 creator A5075480037 @default.
- W4323364275 creator A5078520807 @default.
- W4323364275 creator A5081298406 @default.
- W4323364275 creator A5083466579 @default.
- W4323364275 date "2023-03-06" @default.
- W4323364275 modified "2023-09-28" @default.
- W4323364275 title "Transcriptional adaptation of drug-tolerant<i>Mycobacterium tuberculosis</i>in mice" @default.
- W4323364275 cites W1767652835 @default.
- W4323364275 cites W1864461701 @default.
- W4323364275 cites W1911362206 @default.
- W4323364275 cites W1926302748 @default.
- W4323364275 cites W1938282636 @default.
- W4323364275 cites W1966319077 @default.
- W4323364275 cites W1987681862 @default.
- W4323364275 cites W2002991152 @default.
- W4323364275 cites W2004361822 @default.
- W4323364275 cites W2013100273 @default.
- W4323364275 cites W2019923476 @default.
- W4323364275 cites W2032982721 @default.
- W4323364275 cites W2033228816 @default.
- W4323364275 cites W2042632725 @default.
- W4323364275 cites W2049017883 @default.
- W4323364275 cites W2053867514 @default.
- W4323364275 cites W2055925735 @default.
- W4323364275 cites W2060626299 @default.
- W4323364275 cites W2060650356 @default.
- W4323364275 cites W2065675200 @default.
- W4323364275 cites W2074771787 @default.
- W4323364275 cites W2078663039 @default.
- W4323364275 cites W2080104605 @default.
- W4323364275 cites W2085662298 @default.
- W4323364275 cites W2099183065 @default.
- W4323364275 cites W2102839531 @default.
- W4323364275 cites W2110926912 @default.
- W4323364275 cites W2114104545 @default.
- W4323364275 cites W2120238788 @default.
- W4323364275 cites W2122158116 @default.
- W4323364275 cites W2123624778 @default.
- W4323364275 cites W2125112523 @default.
- W4323364275 cites W2130116522 @default.
- W4323364275 cites W2134345572 @default.
- W4323364275 cites W2141818070 @default.
- W4323364275 cites W2153514608 @default.
- W4323364275 cites W2153619104 @default.
- W4323364275 cites W2156003764 @default.
- W4323364275 cites W2158023121 @default.
- W4323364275 cites W2159394948 @default.
- W4323364275 cites W2160978571 @default.
- W4323364275 cites W2165539745 @default.
- W4323364275 cites W2170535863 @default.
- W4323364275 cites W2179438025 @default.
- W4323364275 cites W2224634640 @default.
- W4323364275 cites W2324008566 @default.
- W4323364275 cites W233147817 @default.
- W4323364275 cites W2460186359 @default.
- W4323364275 cites W2495968991 @default.
- W4323364275 cites W2510019153 @default.
- W4323364275 cites W2527411440 @default.
- W4323364275 cites W2559382600 @default.
- W4323364275 cites W2592038016 @default.
- W4323364275 cites W2594357710 @default.
- W4323364275 cites W2752438189 @default.
- W4323364275 cites W2756187578 @default.
- W4323364275 cites W2953060179 @default.
- W4323364275 cites W2955588301 @default.
- W4323364275 cites W2969496849 @default.
- W4323364275 cites W2972435723 @default.
- W4323364275 cites W2983454386 @default.
- W4323364275 cites W2987076930 @default.
- W4323364275 cites W2996751865 @default.
- W4323364275 cites W2999462941 @default.
- W4323364275 cites W3008621579 @default.
- W4323364275 cites W3011423019 @default.
- W4323364275 cites W3120392574 @default.
- W4323364275 cites W3124177967 @default.
- W4323364275 cites W3146024620 @default.
- W4323364275 cites W3163014973 @default.
- W4323364275 cites W3169468717 @default.
- W4323364275 cites W3172559230 @default.
- W4323364275 cites W3196393882 @default.
- W4323364275 cites W3197600755 @default.
- W4323364275 cites W4206829609 @default.