Resensitizing 'Last-Resort' Antibiotics for Treatment of Infections
upstart writes in with an IRC submission:
Antibiotics are medicines designed to kill bacteria and treat bacterial infections. Antibiotic resistance occurs when bacteria adjust in response to the misuse or overuse of these medicines and it has become one of the biggest public health challenges in this era. At least 2.8 million people get an antibiotic-resistant infection annually in the US, and more than 35,000 people die from it.
The most commonly used antibiotics to treat bacterial infections are -lactams antibiotics, such as cephalosporins and carbapenems. However, their clinical efficacies have been greatly challenged as bacteria produce a resistant determinant that are capable of hydrolysing nearly all -lactams antibiotics, named metallo--lactamases (MBLs). Therefore, the "last-line" antibiotic colistin (COL) has re-emerged as a therapeutic option in response to the outbreak of infections caused by extensively multidrug-resistant Gram-negative pathogens since the mid-1990s. Unfortunately, the efficacy of COL has also been seriously compromised in the regular treatment of lethal bacterial infections, owing to the emergence of another resistant determinant, mobilized colistin resistance (MCR) enzyme in 2015. Owing to the vast structural difference and mode of mechanisms between the two enzymes, it remains an extreme difficulty of adopting a general therapy for infections caused by MBL(s) and MCR(s) co-producing pathogens.
[...] With little remission from the therapeutic reliance on the current pipeline of -lactam antibiotics and COL, the combination therapy consisting of an antibiotic resistance and an antibiotic-resistance breaker offers promising options to narrow the gap between multidrug-resistant bacteria and the development of new antibiotics.
[...] Significantly, the novel combinatorial therapy allows the dose of either MER or COL to be lowered by 32~64 folds to achieve the same level of effectiveness against superbug E. coli CKE, and the development of level of resistant determinant to be significantly slowed down, which will dramatically extend the life cycle of currently used antibiotics.
Journal Reference:
Hongzhe Sun, Qi Zhang, Runming Wang, et al. Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin [open], Nature Communications (DOI: 10.1038/s41467-020-18939-y)
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