Prototype antibiotic annihilates most strains.

• Position: Bacteria

An engineered peptide provides a new prototype for killing an entire category of resistant bacteria by shredding and dissolving their double-layered membranes, which are thought to protect those microbes from antibiotics. The synthetic peptide was effective in lab experiments against antibiotic-resistant Gram-negative bacteria that cause a variety of difficult-to-treat, potentially lethal infections such as pneumonia and sepsis, reports a team led by scientists at The University of Texas MD Anderson Cancer Center, Houston.

"The antibiotic pipeline against multidrug-resistant Gram-negative problem pathogens is a major unmet need in contemporary medicine; as such, our new antimicrobial agent holds immediate promise" says cosenior author Wadih Arap, professor in the Department of Genitourinary Medical Oncology.

Gram-negative bacteria that are highly resistant to existing treatments include E. coli, Acinetobacter baumanii, Pseudomonas aeruglnosa, and Kebsiella pneumonia. These infections often are present in health care settings and most threatening to people with weakened immune systems.

The spiral peptide called KLAKLAKKLAKLAK acts against bacteria by puncturing their lipid bilayer membranes, but has low toxicity toward mammalian cells. These antimicrobial peptides, however, are subject to routine destruction by host enzymes or those generated by the microbe. Combating that effect by increasing the dose heightens both toxicity to other cells and host.

The researchers engineered a version of KLAKLAKKLAKLAK to use in their combination therapies, but had not tested the peptide alone as an antibiotic. The peptide is made of L-amino acids, the building blocks...