ThioredoxinA1 Controls the Oxidative Stress Response of Francisella tularensis Live Vaccine Strain (LVS)

Abstract

The role of thioredoxins in the oxidative stress response of F. tularensis is not known. This study demonstrates that of the two thioredoxins, TrxA1 is vital to counter the oxidative stress in F. tularensis live vaccine strain (LVS).

Diverse roles of low-molecular weight thiol GSH in Francisella’s virulence, location sensing and GSH-stealing from host

“…Together, these results indicate that thioredoxin gene trxA1 is required for virulence in F. novicida and in intramacrophage infection. A recent study confirmed that in F. tularensis LVS, trxA1 (FTL_0611) but not trxA2 (FTL_1224) plays a major role in the oxidative stress response ( Ma et al., 2022 ). A second thioredoxin gene trxA2 is also present in the genome and may have a role in protecting against oxidative stress resistance over long periods of time ( Ma et al., 2022 ; Ma et al., 2019 ).…”

“…A recent study confirmed that in F. tularensis LVS, trxA1 (FTL_0611) but not trxA2 (FTL_1224) plays a major role in the oxidative stress response ( Ma et al., 2022 ). A second thioredoxin gene trxA2 is also present in the genome and may have a role in protecting against oxidative stress resistance over long periods of time ( Ma et al., 2022 ; Ma et al., 2019 ). Interestingly, it has been proposed that the TrxR-Trx systems may be a target for antibiotic development in some bacteria ( Lu and Holmgren, 2014 ).…”

“…Intracellular pathogens must be able to protect against the “respiratory burst” that releases reactive oxygen species (ROS), such as superoxides in the phagosomes of the macrophages ( Murray and Wynn, 2011 ) damaging DNA, lipids and proteins. The oxidative stress response in Francisella , like that in many other Gram-negative bacteria, uses mainly superoxide dismutases and catalases ( Guina et al., 2007 ; Ramond et al., 2014 ; Ma et al., 2016 , 2019 , 2022 ; Honn et al., 2017 , 2012 ; Lenco et al., 2005 ; Marghani et al., 2021 ). The catalase-peroxidase katG ( Table 1 ), which encodes a bifunctional enzyme with both catalase and broad-spectrum peroxidase activity is a known virulence factor of Francisella with mutants in katG being less pathogenic ( Lindgren et al., 2007 ).…”

“…Knockouts of the thioredoxin trxA1 gene have shown significant impacts on the virulence of different pathogenic gram-negative bacteria ( May et al., 2019 a, 2019 b, Carmel-Harel and Storz, 2000 ). trxA1 was identified as being critical in Francisella virulence studies ( Kraemer et al., 2009 ; Ma et al., 2022 ). Kraemer et al.…”

“… 2.4 −1.72 No Change at 4/8 h. Not essential ( Ramsey et al., 2020 ) Not essential ( Ramsey et al., 2020 ) No effect reported ( Ireland et al., 2019 ) trxA1 $ Thioredoxin A1 FTN_1415; FTT_1445; FTL_0611. 1.1 No data No Change at 4/8 h. Essential ( Ramsey et al., 2020 ; Kraemer et al., 2009 ; Ma et al., 2022 ) (−1.69 log2FC). Not essential ( Ramsey et al., 2020 ) No effect reported ( Ireland et al., 2019 ) trxA2 Thioredoxin A2 FTN_0856; FTT_0976; FTL_1224.…”