Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy.

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-á-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.

Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties.

Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads.

Rationally Modified Antimicrobial Peptides from the N-Terminal Domain of Human RNase 3 Show Exceptional Serum Stability.

Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3-also named eosinophil cationic protein-by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages.

Advances in the Dynallax solid-state dynamic parallax barrier autostereoscopic visualization display system.

A solid-state dynamic parallax barrier autostereoscopic display mitigates some of the restrictions present in static barrier systems, such as fixed view-distance range, slow response to head movements, and fixed stereo operating mode. By dynamically varying barrier parameters in real time, viewers may move closer to the display and move faster laterally than with a static barrier system, and the display can switch between 3D and 2D modes by disabling the barrier on a per-pixel basis. Moreover, Dynallax can output four independent eye channels when two viewers are present, and both head-tracked viewers receive an independent pair of left-eye and right-eye perspective views based on their position in 3D space. The display device is constructed by using a dual-stacked LCD monitor where a dynamic barrier is rendered on the front display and a modulated virtual environment composed of two or four channels is rendered on the rear display. Dynallax was recently demonstrated in a small-scale head-tracked prototype system. This paper summarizes the concepts presented earlier, extends the discussion of various topics, and presents recent improvements to the system.

Accommodation and size-constancy of virtual objects.

Accommodation has been suspected as a contributor to size illusions in virtual environments (VE) due to the lack of appropriate accommodative stimuli in a VE for the objects displayed. Previous experiments examining size-constancy in VE have shown that monocular cues to depth that accompany the object are a major contributor to correct size perception. When these accompanying cues are removed perceived size varied with the object's distance from the subject, i.e., visual angle. If accommodation were the dominant mechanism contributing to a visual angle response [due to its action to keep physical objects clear] in this condition, an open-loop accommodation viewing condition might restore size-constancy to this condition. Pinhole apertures were used to open-loop accommodation and examine if size-constancy might be restored when few accompanying monocular cues to depth were present. Visual angle performance when viewing a low cue environment was found with and without the use of the pinhole apertures. Thus, these results signify that accommodation does not play a dominate role in the loss of size-constancy in sparse visual environments often used in VE. These results suggest that size-constancy is driven by the inclusion of the remaining monocular cues to depth in VE as it is in the physical world.