A review on comparative mechanistic studies of antimicrobial peptides against archaea

Increasing multidrug resistance in Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, presents a critical problem. Limited therapeutic options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago. We summarise recent progress in understanding the complex chemistry, pharmacokinetics, and pharmacodynamics of colistin, the interplay between these three aspects, and their effect on the clinical use of this important antibiotic. Recent clinical findings are reviewed, focusing on evaluation of efficacy, emerging resistance, potential toxicities, and combination therapy. In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin.

The archaeal domain is currently divided into two major phyla, the Euryarchaeota and Crenarchaeota. During the past few years, diverse groups of uncultivated mesophilic archaea have been discovered and affiliated with the Crenarchaeota. It was recently recognized that these archaea have a major role in geochemical cycles. Based on the first genome sequence of a crenarchaeote, Cenarchaeum symbiosum, we show that these mesophilic archaea are different from hyperthermophilic Crenarchaeota and branch deeper than was previously assumed. Our results indicate that C. symbiosum and its relatives are not Crenarchaeota, but should be considered as a third archaeal phylum, which we propose to name Thaumarchaeota (from the Greek 'thaumas', meaning wonder).

Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.