This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Groot, R. Articles by Hermans, P. W. Search for Related Content PubMed PubMed Citation Articles by de Groot, R. Articles by Hermans, P. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, 09 1996, 2131-2136, Vol 40, No. 9
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Genetic characterization of trimethoprim resistance in Haemophilus influenzae

R de Groot, M Sluijter, A de Bruyn, J Campos, WH Goessens, AL Smith and PW Hermans
Department of Pediatrics, Sophia Children's Hospital, Erasmus University Rotterdam, The Netherlands.

We previously demonstrated that trimethoprim (Tmp) resistance in Haemophilus influenzae is mediated by chromosomally encoded dihydrofolate reductase (DHFR) with a modified primary structure and distinct kinetic properties. To gain insight into the relationship of the DHFR structure and the level of Tmp resistance that it confers on the host bacterium, we cloned and characterized the folH genes of one Tmp-susceptible and two Tmp-resistant H. influenzae strains. Differences were observed between Tmp-susceptible and Tmp-resistant isolates both in the promoter region and in the coding sequences. The effect of differences between H. influenzae folH genes on Tmp susceptibility was investigated in Escherichia coli. Various folH gene hybrids were constructed, and their influence on Tmp susceptibility was determined. Resistance in E. coli mediated by folH from H. influenzae strain R1047 was associated with alterations in the promoter and the central part of folH. In contrast, the E. coli Tmp resistance phenotype associated with the folH gene of H. influenzae R1042 was characterized by alterations in one or more of three amino acid residues at the C- terminal part of the protein. These data indicate that Tmp resistance is not only related to alterations in the promoter region of the folH gene and the Tmp binding domains at the N-terminal and central part of DHFR. Alterations in the C-terminal part may also cause Tmp resistance, probably as a result of a change in secondary structure and the subsequent loss of Tmp binding affinity.

This article has been cited by other articles:

• Navarro-Martinez, M. D., Navarro-Peran, E., Cabezas-Herrera, J., Ruiz-Gomez, J., Garcia-Canovas, F., Rodriguez-Lopez, J. N. (2005). Antifolate Activity of Epigallocatechin Gallate against Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. 49: 2914-2920 [Abstract] [Full Text]  
• Jones, M. E., Karlowsky, J. A., Blosser-Middleton, R., Critchley, I., Thornsberry, C., Sahm, D. F. (2002). Relationship between Antibiotic Resistance in Streptococcus pneumoniae and That in Haemophilus influenzae: Evidence for Common Selective Pressure. Antimicrob. Agents Chemother. 46: 3106-3107 [Full Text]  
• Enne, V. I., King, A., Livermore, D. M., Hall, L. M. C. (2002). Sulfonamide Resistance in Haemophilus influenzae Mediated by Acquisition of sul2 or a Short Insertion in Chromosomal folP. Antimicrob. Agents Chemother. 46: 1934-1939 [Abstract] [Full Text]