LpxH targeting antibiotics for Gram-negative bacteria

Unmet Need

Antimicrobial resistance of bacteria to antibiotics is a major threat to public health. In 2019, 4.95 million deaths, 64% of all bacterial infection related deaths globally, were attributed to antimicrobial resistance to antibiotics. It is projected by 2050 that 10 million people will die each year due to antimicrobial resistance. Antimicrobial resistance has been on the rise, while the development of new antibiotics has slowed down due to conservation of resistance against antibiotic classes. Since 2017, only 12 antibiotics have been approved and 10 of which belong to classes that have established antimicrobial resistance. Gram-negative bacteria pose a particular challenge due to their unique outer membrane that can make them less susceptible to antibiotics. There is a need for new antibiotics to mitigate the development of antimicrobial resistance.

Technology

Duke inventors have developed a set of new antibiotics for Gram-negative bacteria. This is intended to be used to treat bacterial infections from gram-negative bacteria. Specifically, they have developed a set of sulfonyl piperazine derivatives that target and inhibit the enzyme LpxH, which is required by nearly all clinically relevant Gram-negative bacteria for the maturation of their outer membrane. LpxH has been shown to be required by bacteria for their survival and growth. Importantly, bacteria that express LpxH do not have an alternative enzyme for this critical step in their membrane synthesis. This has been demonstrated in an in vitro killing assay of Klebsiella pneumoniae, clinically relevant Gram-negative bacteria.

Advantages

• Novel class of antibiotics
• No established antimicrobial resistance to these compounds
• Targets an enzyme that is essential for bacterial survival and growth