Description of a functional thioredoxin in Giardia lamblia

Giardia lamblia is an anaerobic/microaerophilic parasite which infects the human small intestine and causes gastrointestinal symptoms, commonly referred to as giardiasis. Due to its anaerobic metabolism, G. lamblia is highly susceptible to oxidative stress, which the parasite counters with its antioxidant defence. One central enzyme of the cellular antioxidant defence is thioredoxin reductase (TrxR) which reduces thioredoxin. Thioredoxin is a versatile reductant of a large subset of cellular proteins, including peroxiredoxins and methionine sulfoxide reductases. Despite this obvious importance, previous attempts to identify a functional thioredxoin in G. lamblia have failed. In this study, we show that the recently discovered thioredoxin-like protein A, TlpA, is a functional thioredoxin which is efficiently reduced by TrxR in assays using the purified recombinant enzymes, and in assays using cell extracts. TlpA, in turn, can fulfil canonical functions of thioredoxins such as reduction of peroxiredoxin and methionine sulfoxide reductase. In addition, TlpA modulates the detrimental side activity of TrxR, i.e. reduction of molecular oxygen to superoxide, by mediating or catalysing the reduction of superoxide to H2O2. We propose to rename TlpA to thioredoxin 1 (Trx1).