Linezolid more effective than vancomycin in treating ventilated patients with MRSA pneumonia: Study

In continuation of my update on Linezolid and Vancomycin...

Linezolid more effective than vancomycin in treating ventilated patients with MRSA pneumonia: Study

Plectasin - a new weapon against highly resistant microbes ?..

We know that Plectasin, found in Pseudoplectania nigrella (see picture), is the first defensin to  be isolated from a fungus. Plectasin has a chemical structure resembling defensins found in spiders, scorpions, dragonflies and mussels. In laboratory tests, Plectasin was especially active in inhibiting the growth of the common human pathogen Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin has a low toxicity in mice, and cured them of peritonitis and pneumonia caused by S. pneumoniae as efficiently as vancomycin and penicillin, suggesting that it may have therapeutic potentia.

Now researchers lead by Prof. Dr. Hans-Georg Sahl of   Universities of Bonn, Utrecht, Aalborg and of the Danish company Novozymes AS have shed light on how the substance Plectasin,  destroy highly resistant bacteria. As per the claim by the researchers Plectasin binds to a cell-wall building block called lipid II and thus prevents it from being incorporated and thus disrupting the forming of the cell wall in bacteria so that the pathogens can no longer divide. 

In this process, plectasin behaves like a thief which steals the stones off a mason. 'It binds to a cell-wall building block called lipid II and thus prevents it from being incorporated ,' Professor Sahl explains. 'However, bacteria cannot live without a cell wall.' It comes as no surprise that the most famous antibiotic penicillin also inhibits cell-wall synthesis...

Researchers claims that, plectasin is more similar in its mode of action to another widely used drug, vancomycin. Vancomycin had been the drug of choice in combating MRSA strains since the 1980s. Meanwhile, though, there are more and more bacteria that are also resistant to vancomycin. 'However, these strains are still susceptible to plectasin,' Dr. Tanja Schneider emphasises. Nevertheless, there is no permanent solution to the resistance problem even with a new antibiotic . 'It is always just a question of time until the pathogens mutate and become insensitive ,' she says. 'It's a never ending arms race..' authors conclude that plectasin will be promising lead compound for new antibiotics...

Ref : http://www.sciencemag.org/cgi/content/abstract/328/5982/1168

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA 

2-aminoimidazole/triazole conjugate re-sensitizes multi-drug resistant strains of bacteria to the effects of conventional antibiotics...

We know that infections from antibiotic-resistant bacteria such as MRSA  are especially difficult to get rid of because the bacteria can attach to surfaces and then create biofilms, sticky layers of cells that act as a shield and prevent antibiotics from destroying the bacteria underneath. While a limited number of existing antibiotics may destroy part of the biofilm, enough bacteria survive to create a recurring infection as soon as antibiotic therapy stops, and over time the surviving bacteria build resistance to that antibiotic. Though I have covered some recent developments in the MRSA field, the following findings are  really interesting for me...

Now researchers lead by Dr. Christian Melander, from North Carolina State University have found that, 2-aminoimidazole/triazole conjugate will  re-sensitize multi-drug resistant strains of bacteria to the effects of conventional antibiotics (including MRSA and multi-drug resistant Acinetobacter baumannii), apart from the synergistic effect between  the  conjugate and antibiotics toward dispersing pre-established biofilms. 

Melander and his team, in collaboration with NC State biochemist John Cavanagh, found that pre-treating the bacteria with their compound and then introducing the antibiotic penicillin one hour later increased the penicillin's effectiveness 128-fold, even when the bacteria was penicillin resistant. The antibiotics also provided a 1,000-fold enhancement to the ability of the 2-aminoimidazole to disperse biofilms. 

Researchers conclude that, compound cooperates with conventional antibiotics, overcoming an infectious threat that would otherwise persist if treated with either agent individually.....

Ref : http://aac.asm.org/cgi/content/abstract/AAC.01418-09v1

Novel nanotechnology heals abscesses caused by resistant staph bacteria

Novel nanotechnology heals abscesses caused by resistant staph bacteria

MSRA can be stopped before it becomes dangerous ....

In continuation of my update on MRSA (methicillin-resistant Staphylococcus aureus), I found the following info interesting.

C. Jeffrey Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein (as against the belief that, staph infections are caused by many bacterial cells that signal each other to emit toxins. The signaling process is called quorum sensing). The most significant results from the researchers are :

1. isolation of Staphylococcus aureus bacteria in individual (isolation of an individual bacterium
previously had been achieved only computationally);

2. demonstration of release of signaling peptides from a single cell, not a quorum &

3. introduction of an inexpensive, very low-density lipoprotein (VLDL) to bind to the
messenger peptide, they stopped the single cell from reprogramming itself.

One aspect of experimental rigor was the team's ability to organize living cells into a nanostructured matrix. The researchers has already done it with yeast, and just extended the process to bacteria. Researchers are optimistic about finding a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. If they achieve what they are optimistic, so there will selectivity of targeting the bacteria (human gastro-intestinal system contains many useful bacteria) which in my opinion will be a remarkable feat....

Ref : http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.264.html

Discovery Of Novel New Class of Antimicrobial Agents... ......

We know that most of the bacteria are getting resistant to the present drugs and there is an urgent need to find a solution for resistant bacteria. Inn this global fight against resistant bacteria many companies are trying different ways and now Chaperone Technologies, Inc has come up with something innovative and interesting way, i.e., the company is trying to develop antimicrobial compounds that work by inhibiting bacterial hsp70 proteins (an entirely new mechanism of action).

Chaperone’s antimicrobial program focuses on development of peptide as well as small molecule hsp70 inhibitor drugs that block the effect of this important class of molecular “chaperones” whose role is to help mediate or respond to toxic misfolded proteins within bacteria. Inhibition of this critical bacterial protein has been proven to kill bacterial pathogens. Besides antimicrobials, the inhibition of hsp70 molecular chaperone proteins present in other cell-types has a range of therapeutic applications that are being investigated by the company.

Using sophisticated computerized molecular modeling techniques, proprietary high-throughput screening tools developed by Chaperone and other approaches, the company has significantly expanded its library of novel hsp70 inhibitor compounds including CHP-267 and CHP-281, just two of the many promising drug candidates from this highly promising family of small molecule inhibitors discovered by the Company. Chaperone is looking at hsp70 inhibitors as stand alone antimicrobial agents as well as in combination with other antimicrobials (e.g., Finafloxacin.HCl : see the structure -which is under phase II clinical trials). The company recently received a US Patent covering a method of significantly amplifying the effectiveness of other antimicrobials by combining their use with that of an hsp70 inhibitor. Combining a bacterial hsp70 inhibitor with another antimicrobial yields increased bacterial killing of clinically important pathogens and the potential for combination therapy.

Chaperone’s drug candidates have been proven effective against dangerous bacteria such as MRSA, acinetobacter, and vancomycin resistant enterococci. When combined with other antibiotics, Chaperone’s compounds stimulate powerful antibiotic synergy, providing superior efficacy even while using significantly lower doses of the combined agents.

Source : http://www.biospace.com/news_story.aspx?NewsEntityId=118501