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Quinoxaline 1, 4-dioxides (QdNOs) has been used in animals as antimicrobial agents and growth promoters for decades. However, the resistance to QdNOs in pathogenic bacteria raises worldwide concern but it is barely known. To explore the molecular mechanism involved in development of QdNOs resistance in  Escherichia coli,  6 strains selected by QdNOs  in vitro  and 21 strains isolated from QdNOs-used swine farm were subjected to MIC determination and PCR amplification of  oqxA  gene. A conjugative transfer was carried out to evaluate the transfer risk of QdNOs resistant determinant. Furthermore, the transcriptional profile of a QdNOs-resistant  E. coli  (79O4-2) selected  in vitro  with its parent strain 79–161 was assayed with a prokaryotic suppression subtractive hybridization (SSH) PCR cDNA subtraction. The result showed that more than 95% (20/21) clinical isolates were  oqxA  positive, while all the 6 induced QdNOs-resistant strains carried no  oqxA  gene and exhibited low frequency of conjugation. 44 fragments were identified by SSH PCR subtraction in the QdNOs-resistant strain 79O4-2. 18 cDNAs were involved in biosynthesis of Fe-S cluster ( narH ), protein ( rpoA, trmD, truA, glyS, ileS, rplFCX, rpsH, fusA ), lipoate ( lipA ), lipid A ( lpxC ), trehalose ( otsA ), CTP( pyrG ) and others molecular. The 11 cDNAs were related to metabolism or degradation of glycolysis ( gpmA  and  pgi ) and proteins ( clpX, clpA, pepN and fkpB ). The  atpADG  and  ubiB  genes were associated with ATP biosynthesis and electron transport chain. The pathway of the functional genes revealed that  E. coli  may adapt the stress generated by QdNOs or develop specific QdNOs-resistance by activation of antioxidative agents biosynthesis (lipoate and trehalose), protein biosynthesis, glycolysis and oxidative phosphorylation. This study initially reveals the possible molecular mechanism involved in the development of QdNOs-resistance in  E. coli , providing with novel insights in prediction and assessment of the emergency and horizontal transfer of QdNOs-resistance in  E. coli .

Development of Quinoxaline 1, 4-Dioxides Resistance in Escherichia coli and Molecular Change under Resistance Selection