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Antibiotics are conventionally used to treat urinary tract infections (UTIs), but increases in bacterial resistance to commonly used antibiotics means that new therapeutic strategies for

bacterial infections must be devised. Corrine K. Cusumano et al. now describe an alternative approach for treating and preventing infections caused by uropathogenic Escherichia coli (UPEC)

(Sci. Transl. Med. 3, 109ra115).

The team had previously designed a range of mannoside compounds to target a UPEC adhesin called FimH, which is necessary for the invasion, colonization and the formation of intracellular

bacterial communities in the bladder epithelium. Cusumano et al. have now investigated the efficacy of these compounds to inhibit UPEC biofilm production in vitro, allowing them to identify

one that showed the best activity at low doses and was orally bioavailable. This compound treated chronic cystitis in a mouse model, showing improved efficacy compared with the standard

antibiotic treatment for UTIs (trimethoprim-sulfamethoxazole; TMP-SMZ), and could also be used prophylactically. In addition, the mannoside compound synergized with TMP-SMZ by trapping the

bacteria in the bladder lumen, where they are exposed to maximum doses of the antibiotic.

The authors also developed further mannoside compounds with improved pharmacokinetics and efficacy in vivo, which could be further investigated for their therapeutic potential in women with

recurrent UTIs.

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