Alternative strategies to tackle antibiotics resistance

Abstract

Alternative strategies to tackle antibiotics resistance Peng Gao1, Hongzhe Sun3, Julian Davies4, Richard Yi Tsun Kao1,2 1Department of Microbiology,2State Key Laboratory for Emerging Infectious Disease and the Research Centre of Infection and Immunology, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong. 3Department of Chemistry, The University of Hong Kong. 4Department of Microbiology and Immunology, The University of British Columbia, Vancouver B.C. Canada (rytkao@hku.hk) The emergence of multidrug resistant bacteria including methicillin resistant Staphylococcus aureus (MRSA) is the inevitable outcome of indiscriminate use of antibiotics by mankind. As the World Health Organization has declared antimicrobial resistance one of the biggest threats to global health, alternate therapeutic strategies that will not cause resistance are urgently needed to fight against MDR bacteria. Two strategies, restore the sensitivity of resistant bacteria to known antibiotics and suppress the virulence of bacteria. A known drug colloidal bismuth subcitrate, can repurpose meropenem to the Enterobacteriaceae producing metallo-β-lactamases, such as NDM-1 E. coli. The unique mechanism is one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. Two novel compounds could reduce MRSA virulence through different ways. NP16 reduce the “shield” of MRSA, staphyloxancin, and increased the sensitivity of bacteria to our immune system; M21 disarms MRSA by suppressing multiple virulence factors production and reduces the pathogenicity of bacteria. They all showed promising effect against pathogens in vivo. Since this type of compounds have two advantages over classic antibiotics. Firstly, such agents will not have selective pressure for raising resistance mutant. Secondly, the specificity of such agents should preserve the bacteria that constitute the normal flora. It is anticipated that they will become a new therapeutic strategies.