Point Mutations in the folP Gene Partly Explain Sulfonamide Resistance of Streptococcus mutans

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.

Aery, SahilUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (författare)
Rwenyonyi, Charles (författare)
Swedberg, GöteUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)goteswed (författare)
Kironde, Fred (författare)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Ingår i:International Journal of Microbiology: Hindawi Limited2013, s. 367021-1687-918X1687-9198

Av författaren/redakt...: Buwembo, William; Aery, Sahil; Rwenyonyi, Charl ...; Swedberg, Göte; Kironde, Fred

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Mikrobiologi ino ...

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