immune response, page-4

The Acinetobacter and Pseudomonas bugs are part of the 'gram negative bacteria' group.

I was reflecting on this and asked, if this is the case, why haven't other companies besides Medimmune, jumped on the Acinetobacter target?.... OR have they? Don't you find this odd? I know what i think, but what do other's think about this?

If you read the CEO transcript (there was a hint in that document) you'll note that Medimmune's interest for now is solely on the Pseudomonas bug. Why only this bug? Is that now about to change?

http://www.theceotranscript.com.au/interviews/phylogicaaugust2010.pdf

Perhaps I'm reading too much into this, but, I'm curious to hear other's thoughts on this are.

Looks to me like Phylogica’s peptides are about to make a BIG splash in a BIG way in this space. Have a read of the section below on the Acinetobacter baumannii bug and the advances Phylogica have made.

Cell-based Screening Using Phage Display

Phylogica’s Antimicrobial Discovery subsidiary, Dynamic Microbials Ltd, has conducted a direct, cell-based screen to identify Phylomer® peptides which have activity against bacteria involved in multidrug resistant nosocomial infections.

To identify peptides which bind to bacteria, a phage display library of 51 million Phylomer® peptides was selected sequentially by biopanning on live Acinetobacter baumannii, a species of bacteria involved in nosocomial infections. A total of 101 Phylomer® peptides were obtained which bound to A. baumannii. These peptides were used to design a series of 280 overlapping synthetic peptides, which were then tested for antimicrobial activity (Figure 6).

Figure 6: Selected Phylomer® peptides inhibit growth of
Acinetobacter baumannii

Several of these Phylomer® peptides (shown in blue) could inhibit the growth of bacteria as well as or better than known antimicrobial peptides (shown in brown) at an equivalent concentration or Ampicillin which was tested at two different concentrations.

Bactericidal activity was confirmed in live cell plating assays, in which 100% of bacteria were killed in the presence of Phylomer® peptides at nM to low µM concentration. The active Phylomer® peptides were divided into the rapid bactericidal, slow bactericidal and bacteriostatic/delayed bactericidal peptides. Rapid bactericidal activity occurred within 5 minutes of co-incubation and was observed for 3 out of 14 active Phylomer® peptides.

Assessment of mammalian toxicity by red blood cell haemolysis showed no measurable toxicity for 7 of the active Phylomer® peptides (a selection of peptides shown in Figure 6)

Figure 7: Selection of Phylomer® peptides with potent antimicrobial activity and varying degrees of haemolytic activity (MHC10 = Minimal Haemolytic Concentration, i.e. high MHC10 is considered to be favourable since a higher concentration is required to cause damage)

The screen resulted in the isolation of 14 Phylomer® peptides with potent antimicrobial activity against the gram-negative bacterium A. baumannii. Further characterisation showed that biopanning the Phylomer® library had produced a diversity of antimicrobial peptide with varying degrees of cross-activity against the gram-positive bacterium S. aureus (Figure 7). Phylomers were identified from this screen which were more potent than the well characterised natural antimicrobial peptide tachyplesin, which has an MIC against A. Baumannii of 1.75µM.

Pilot experiments with the most potent Phylomer® peptide Ac14s3 showed high antimicrobial activity at low nanomolar concentration against clinical multi-resistant
bacterial isolates. An anitmicrobial phylomer has shown activity in vivo in an animal model of pneumonia.

http://www.phylogica.com/media/PHA16789-A3-Flyer-Alterations-Feb-2010.pdf