MtlD as a therapeutic target for intestinal and systemic bacterial infections

The ability to treat infections is threatened by the rapid emergence of antibiotic resistance. Mannitol is a polyol used in human medicine and the food industry. During catabolism of mannitol, many bacteria transport mannitol across the inner membrane forming the toxic intermediate mannitol-1-phosphate (Mtl-1P). Mtl-1P must be processed by mannitol dehydrogenase (MtlD) or it accumulates intracellularly, causing growth attenuation. We test and confirm here that <i>mtlD</i> mutants of <i>Escherichia coli</i> (including UPEC, and EHEC), <i>Salmonella</i> (including serovars Typhi, and Paratyphi A, B, and C), <i>Cronobacter</i>, and <i>Pseudomonas</i> experience mannitol sensitivity <i>in vitro</i>. Furthermore, providing mannitol in drinking water can alleviate both gastrointestinal and systemic <i>Salmonella</i> infections in mice. This suggests that inhibition of MtlD could be a viable antimicrobial strategy.