Molecular Characterization of Cotrimoxazole Resistance Genes and Their Associated Integrons in Clinical Isolates of Gram-Negative Bacteria from Tanzania

Abstract

Cotrimoxazole is widely used, particularly as a prophylactic drug in HIV patients. We assessed resistance mechanisms among cotrimoxazole resistant-Gram negative bacterial isolates (n = 123) obtained from blood (n = 69) and urine (n = 54) from Tanzanian patients. sul genes were detected in 98% (121/123) of the isolates. Coexistence of sul1 and sul2 was common (49/123). The dfr genes were found in 63% (77/123) of all isolates. sul1, dfrA15, and dfrA5 genes predominated among Klebsiella pneumoniae, while sul2 and dfrA1 genes were frequent in Escherichia coli isolates. Two isolates, both K. pneumoniae, carried sul3. Integrons were detected in 81.3% (100/123) of all isolates. Class 1 integrons were found in 95% (42/44), 53% (23/43), and 80.6% (25/31) of K. pneumoniae, E. coli, and other Enterobacteriaceae isolates, respectively. Class 2 integrons were found in 14% of E. coli, but not in K. pneumoniae. All sul1 genes in K. pneumoniae were carried in class 1 integrons. Gene cassette arrays dfrA5 and dfrA15-aadA1 were most frequently associated with class 1 integrons, while class 2 integrons contained only dfrA1-sat2-aadA1 gene cassettes. This is the first report of sul3 gene in K. pneumoniae from human sources. The finding that mechanisms differ between E. coli and K. pneumoniae may broaden our understanding of cotrimoxazole resistance.

The Molecular Epidemiology of Resistance to Antibiotics among Klebsiella pneumoniae Isolates in Azerbaijan, Iran

“…Based on this study, the sul1 gene has the highest frequency in K. pneumoniae resistance to co-trimoxazole. e rate of sul1 (71%) was higher than sul2 (43%) and sul3 (7%), which is in accordance with a study from Tanzania [50]. e frequency of sul genes in a previous study in Iran on Escherichia coli isolates was close to our study [51].…”

The Resistome, Mobilome, Virulome and Phylogenomics of Multidrug-Resistant Escherichia coli Clinical Isolates from Pretoria, South Africa

“…The sul and dfr gene cassettes identified in the isolates were previously reported in a study done in Enterobacteriaceae in Tunisia 55 . However, these genes have only been reported in Streptococcus pneumoniae isolates from South Africa 56 , whilst the rare sul3 gene was only recently reported in clinical isolates in Tanzania 57 . The genetic environment of sul 1 and sul2 genes were mostly consistent, with sul 1 being mostly associated with QacEΔ1 and aadA genes ( aadA1/5:QacEΔ1:sul1 ) and sul2 being always found with aph genes ( aph(6)-Id:aph(3 ′) -Ib:sul2 ) within composite transposons or ISs.…”

Molecular Surveillance and Dissemination of Klebsiella pneumoniae on Frequently Encountered Surfaces in South African Public Hospitals

“…Since 1968, sulfamethoxazole and trimethoprim have been used in combination, to treat UTIs, enteric bacterial infections and respiratory tract infections (Frank et al, 2007;Manyahi et al, 2017). This antibiotic combination is known as cotrimoxazole, and each antibiotic disrupts a different enzyme involved in distinct steps in the folic acid pathway (Frank et al, 2007;Huovinen, 2001).…”

“…Sulfamethoxazole inhibits dihydropteroate synthase (DHPS) whereas trimethoprim inhibits dihydrofolate reductase (DHFR). Although resistance can happen in various ways, in Gram-negative enteric bacteria, acquisition of drug-resistant enzymes is the most common mechanism (Frank et al, 2007;Manyahi et al, 2017).…”

“…Resistance is gained by acquiring genes that encode enzymes that are naturally resistant to the antibiotics, thus making them ineffective (Frank et al, 2007). These modified enzymes (DHFR and DHPS) are encoded by the dfr and sul genes for trimethoprim and sulfamethoxazole, respectively (Manyahi et al, 2017). More than 30 dfr genes have been described compared to only three sul genes (Shin et al, 2015).…”