| 1. |
- Buwembo, William, et al.
(author)
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Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans
- 2013
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In: International Journal of Microbiology. - : Hindawi Limited. - 1687-918X .- 1687-9198. ; 2013, s. 367021-
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Journal article (peer-reviewed)abstract
- Cotrimoxazole inhibits dhfr and dhps and reportedly selects for drug resistance in pathogens. Here,Streptococcus mutansisolates were obtained from saliva of HIV/AIDS patients taking cotrimoxazole prophylaxis in Uganda. The isolates were tested for resistance to cotrimoxazole and theirfolPDNA (which encodes sulfonamide-targeted enzyme dhps) cloned in pUC19. A set of recombinant plasmids carrying different point mutations in cloned folP were separately transformed intofolP-deficientEscherichia coli. Using sulfonamide-containing media, we assessed the growth offolP-deficient bacteria harbouring plasmids with differingfolPpoint mutations. Interestingly, clonedfolPwith three mutations (A37V, N172D, R193Q) derived fromStreptococcus mutans8 conferred substantial resistance against sulfonamide tofolP-deficient bacteria. Indeed, change of any of the three residues (A37V, N172D, and R193Q) in plasmid-encodedfolPdiminished the bacterial resistance to sulfonamide while removal of all three mutations abolished the resistance. In contrast, plasmids carrying four other mutations (A46V, E80K, Q122H, and S146G) infolPdid not similarly confer any sulfonamide resistance tofolP-knockout bacteria. Nevertheless, sulfonamide resistance (MIC = 50 μM) offolP-knockout bacteria transformed with plasmid-encodedfolPwas much less than the resistance (MIC = 4 mM) expressed by chromosomally-encodedfolP. Therefore,folPpoint mutations only partially explain bacterial resistance to sulfonamide.
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| 2. |
- Wilén, Maria, et al.
(author)
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Cotrimoxazole resistance of Streptococcus pneumoniae and commensal streptococci from Kampala, Uganda
- 2009
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 41:2, s. 113-121
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Journal article (peer-reviewed)abstract
- Trimethoprim sulfamethoxazole (cotrimoxazole, CTX) is used frequently as part of standard medical care for people living with HIV/AIDS in Africa. The mechanisms of resistance to sulfonamides and trimethoprim in commensal streptococci from Uganda were determined and compared to S. pneumoniae. Commensal streptococci showing high-level resistance to cotrimoxazole were cultured and analysed for species identity and polymorphisms in the genes coding for dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Seven isolates of S. pneumoniae from blood and cerebrospinal fluid (CSF) were similarly examined. There was considerable polymorphism in both DHPS and DHFR. In DHFR, the mutations E20D and I100L were present in all sequenced isolates. Other mutations such as L135F, and different substitutions in D92, were frequent. The most common DHPS variants had 2 serine residues added after amino acid 60, or arginine and proline added after amino acid 59. In addition, 3 new insertions/substitutions were found. There were no obvious differences between the mutation patterns in S. pneumoniae and commensal streptococci, suggesting that the chromosomal mutations have been spread by transformational interchanges of DNA among related organisms.
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| 3. |
- William, Buwembo, et al.
(author)
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Cotrimoxazole Prophylaxis Specifically Selects for Cotrimoxazole Resistance in Streptococcus mutans and Streptococcus sobrinus with Varied Polymorphisms in the Target Genes folA and folP
- 2012
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In: International Journal of Microbiology. - : Hindawi Limited. - 1687-918X .- 1687-9198. ; , s. 916129-
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Journal article (peer-reviewed)abstract
- The selection of antibiotic resistance by cotrimoxazole prophylaxis was evaluated, and we characterized the mechanism of cotrimoxazole resistance in Streptococcus mutans and Streptococcus sobrinus. In vitro susceptibility to six antibiotics was evaluated on 64 mutans streptococci group (MSG) isolates from a cotrimoxazole prophylaxis group and compared to 84 MSG isolates from a nonprophylaxis group. The folA and folP genes were sequenced and compared with reference sequences at NCBI. Only resistance to cotrimoxazole was significantly higher in the prophylaxis group (54.7% versus 15.5%, OR = 6.59, 95% CI: 2.89-15.3, P < 0.05). Resistance to amoxicillin, ceftriaxone, chloramphenicol, erythromycin, and tetracycline was 1.4%, 25.5%, 6.2%, 6.5%, and 29.6% of the isolates, respectively. Considerable polymorphisms were found in the folP gene in S. mutans, but this could not be linked to sulfonamide drug resistance. No variation was seen in folP or folA genes of S. sobrinus. Genetic transfer of folate pathway genes seems unlikely in these isolates.
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