Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to nitazoxanide and metronidazole

Abstract

These results suggest that resistance formation in Giardia to nitazoxanide and metronidazole is correlated with altered expression of genes involved in stress response such as heat-shock proteins.

Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

“…These data suggest that the mechanisms of 5-NI drug resistance overlap in different microbes, but they are not the same for different structural classes of nitro drugs. Specific mechanisms of 5-NI drug resistance are beginning to be understood in protozoa (28), although it is likely that other mechanisms remain to be discovered, as also suggested by the differential expression of several genes whose products can reduce and activate 5-NI drugs, as well as other genes coding for proteins involved in stress responses, in the present and in prior studies (25,26). However, in many clinical situations of treatment failure with Mz, at present it is unlikely that a specific drug resistance mechanism can be identified or the consequences for crossresistance predicted.…”

“…To further characterize the new Mz r lines, we assessed the expression levels of genes associated with Mz activation and resistance and compared them with those reported for the previously published Mz r lines. PFOR and ferredoxin have a key role in nitro drug activation and are decreased in certain Mz r lines, including 106-2ID 10 , but not others (22,25). Consistent with this variability, PFOR expression levels differed between the two new Mz r lines, since WB-M1 had a significant, albeit modest, decrease, while WB-M2 had no significant change (Fig.…”

“…Together, these results suggest that the apparent rarity of clinical Mz resistance in Giardia despite the widespread use of Mz in the treatment of giardiasis can be explained, at The metabolism of Mz r Giardia is altered in important ways, since prior studies had shown that several lines of Mz r Giardia proliferate more slowly in vitro than their isogenic Mz s counterparts (11). For example, resistance to 5-NI drugs has been associated with decreased expression and activity of a key enzyme, PFOR, involved in the final steps of ATP generation from glucose (8,11,25). Indeed, we found that several Mz r lines consumed less glucose than their parental Mz s lines and, importantly, glucose promoted parasite attachment, thus providing a possible explanation for the attachment defect observed in Mz r lines.…”

Comparison of efficiency of various DNA extraction methods from cysts ofGiardia intestinalismeasured by PCR and TaqMan real time PCR

“…However, these techniques might not be sensitive enough to detect cysts in environmental samples (rochelle et al, 1997;Haque et al, 2007). recently, a few Pcr-based techniques have been developed for detection and genotypic characterization of G. intestinalis (Yong et al, 2002 ;muller et al, 2008 ;Ajjampur et al, 2009 ;tashima et al, 2009). in water samples G. intestinalis cysts occur in very low concentration (kaucner & stinear, 1998), so the recovery of this pathogen dnA during dnA extraction becomes important.…”

The Effects of Concomitant Giardia intestinalis Infection on Acute Gastrointestinal Toxicity in Rats Undergoing Pelvic Irradiation

“…Transcriptional changes occurring under various stress conditions in Giardia have been examined in a number of studies conducted recently (20)(21)(22)(23)(24)(25). Nevertheless, no study that evaluates Giardia infection following the application of UV radiation histologically has been encountered in the literature.…”