@article{fdi:010035620,
  title = {{L}eishmania infantum amastigotes resistant to nitric oxide cytotoxicity: {I}mpact on in vitro parasite developmental cycle and metabolic enzyme activities},
  author = {{H}olzmuller, {P}hilippe and {H}ide, {M}allorie and {S}ereno, {D}enis and {L}emesre, {J}ean-{L}oup},
  editor = {},
  language = {{ENG}},
  abstract = {{N}itric oxide ({NO}) has been demonstrated to be the principal effector molecule mediating intracellular killing of {L}eishmania. {T}he free radical characteristic of {NO} prevented direct induction of resistance in {L}eishmania wild-type parasites. {S}tarting from the previous observation that antimony-resistant amastigotes of {L}eishmania infantum were not affected by {NO}-induced apoptotic death, we used a continuous {NO} pressure protocol and succeeded in inducing {NO} resistance in amastigote forms of {L}. infantum. {T}wo clones resistant to 50 mu {M} ({L}i{NOR}50) and 100 mu {M} ({L}i{NOR} 100) of the {NO} donor {DETA}/{NONO}ate, derived from parental clone weakly resistant to trivalent antimony ({L}i{S}b{IIIR}4), were selected and analysed. {B}oth clones were also resistant to other {NO} donors, particularly {SNAP} {I}n the absence of potassium antimonyl tartrate, all clones ({L}i{S}b{IIIR}4, {L}i{NOR}50 and {L}i{NOR}100) lost their antimony resistance almost totally. {I}nterestingly, the parasitic developmental life cycle of {NO}-resistant mutants was dramatically disturbed. {NO}-resistant amastigotes differentiated more rapidly into promastigotes than the wild-type ones. {N}evertheless, {NO}-resistant amastigotes produce a maximal number of parasites 1.5-2 times lower than the wild-type whereas, after differentiation, {NO}-resistant promastigotes produced more cells than the wild-type. {W}e showed that this last phenomenon could be a consequence of the overexpression of parasitic enzymes involved in both glycolysis and respiration processes. {NO}-resistant amastigotes overexpressed three enzymes: cis-aconitase, glyceraldehyde-3-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. {T}he two first enzymes are {NO} molecular targets which could be directly involved in {NO} resistance and the third one could interfere in modifying {L}eishmania metabolism. (c) 2005 {E}lsevier {B}.{V}. {A}ll rights reserved.},
  keywords = {{L}eishmania ; nitric oxide ; chemoresistance ; developmental cycle ; apoptosis ; enzyme overexpression ; cis aconitase ; {G}3{PDH} ; 6{PGDH}},
  booktitle = {},
  journal = {{I}nfection {G}enetics and {E}volution},
  volume = {6},
  numero = {3},
  pages = {187--197},
  ISSN = {1567-1348},
  year = {2006},
  DOI = {10.1016/j.meegid.2005.03.003},
  URL = {https://www.documentation.ird.fr/hor/fdi:010035620},
}