Reverse transcriptase inhibitors prevent liver abscess formation during Escherichia coli bloodstream infection.
Reverse transcriptase inhibitors prevent liver abscess formation during Escherichia coli bloodstream infection.
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DOI：
10.1073/pnas.2319162121
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发表时间：
2024-01-23
影响因子：
11.1
通讯作者：
Waldor, Matthew K.
中科院分区：
文献类型：
--
作者：
Hullahalli, Karthik;Dailey, Katherine G.;Hasegawa, Yuko;Johnson, Welkin E.;Waldor, Matthew K.
The presence of bacteria in the bloodstream is associated with severe clinical outcomes. In mice, intravenous inoculation of Escherichia coli can lead to the formation of macroscopic abscesses in the liver. Abscesses are regions of severe necrosis and consist of millions of bacteria surrounded by inflammatory immune cells. Liver abscess susceptibility varies widely across strains of mice, but the host factors governing this variation are unknown. Here, we profiled hepatic transcriptomes in mice with varying susceptibility to liver abscess formation. We found that transcripts from endogenous retroviruses (ERVs) are robustly induced in the liver by E. coli infection and ERV expression positively correlates with the frequency of abscess formation. Hypothesizing that ERV-encoded reverse transcriptase may generate cytoplasmic DNA and heighten inflammatory responses, we tested whether nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) influence abscess formation. Strikingly, a single NRTI dose administered immediately following E. coli inoculation prevented abscess formation, leading to a concomitant 100,000-fold reduction in bacterial burden. We provide evidence that NRTIs inhibit abscess formation by preventing the tissue necrosis that facilitates bacterial replication. Together, our findings suggest that endogenous reverse transcriptases drive inflammatory responses during bacterial bloodstream infection to drive abscess formation. The high efficacy of NRTIs in preventing abscess formation suggests that the consequences of reverse transcription on inflammation should be further examined, particularly in infectious diseases where inflammation drives negative clinical outcomes, such as sepsis.
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影响因子：
1
作者：
Holec AD;Mandal S;Prathipati PK;Destache CJ
通讯作者：
Destache CJ
DOI：
10.1007/s00018-008-8497-0
发表时间：
2008-11
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Stocking C;Kozak CA
通讯作者：
Kozak CA
影响因子：
64.5
作者：
Lima-Junior DS;Krishnamurthy SR;Bouladoux N;Collins N;Han SJ;Chen EY;Constantinides MG;Link VM;Lim AI;Enamorado M;Cataisson C;Gil L;Rao I;Farley TK;Koroleva G;Attig J;Yuspa SH;Fischbach MA;Kassiotis G;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
29.7
作者：
Kassiotis G
通讯作者：
Kassiotis G
影响因子：
32.4
作者：
Treger, Rebecca S.;Pope, Scott D.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko