Re: new drug screening for chronic staph infection

[Guest guest]

This is particularly interesting because they found one compound

more active against their SCVs than it was previously reported to be

against normal Sa (which, as a caveat, obviously were not isogenic

to this groups SCVs):

" Thiadiazolotriazine 2 has been reported by Eli Lilly (US 4,042,372)

to have moderate activity (10–100 ìg ml & #8722;1) against S. aureus and E.

coli among others. However, we found 2 to have greater activity

against the S. aureus strains used in the present study. "

> Cool!

>

> ==============================

>

> FEMS Immunol Med Microbiol. 2005 Jun 14; [Epub ahead of print]

> Related Articles, Links

>

>

> Identification of antimicrobial compounds active against

> intracellular Staphylococcus aureus.

>

> Malouin F, Brouillette E, ez A, Boyll BJ, Toth JL, Gage JL,

> NE.

>

> Centre d'Etude et de Valorisation de la Diversite Microbienne

> (CEVDM), Departement de biologie, Faculte des sciences, Universite

> de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., Canada J1K

> 2R1.

>

> Small-colony variants (SCVs) of Staphylococcus aureus exhibit

> characteristics of bacteria that can penetrate mammalian cells and

> remain intracellular and innocuous for indefinite periods. These

> properties make SCVs a convenient tool that can be used to

identify

> new antibacterial agents having activity against intracellular,

> quiescent bacteria. Agents active against SCVs could be useful in

> the treatment of chronic staphylococcal infections such as bovine

> mastitis. An hemB deletion mutant of S. aureus Newbould, a bovine

> mastitis isolate, having a stable, genetically defined SCV

> phenotype, was used in a screening program to identify compounds

> active against intracellular, gram-positive bacteria. Out of more

> than 260,000 compounds screened, nine compounds having the desired

> properties were identified. The range of MICs against gram-

positive

> bacteria was 0.12-32mugml(-1). One of the compounds (no. 8) showed

> excellent activity against gram-positive (MICs 0.12mugml(-1)) and

> gram-negative (MICs 0.12-4mugml(-1)) bacteria. Each of the nine

> compounds demonstrated efficacy in a neutropenic mouse thigh

> infection model. Two compounds, including compound no. 8, reduced

> numbers of bacteria in a mouse mastitis model of infection.

> Application of a stepwise screening process has identified lead

> compounds that may be useful for treating persistent,

intracellular

> infections.

>

> PMID: 15963705 [PubMed - as supplied by publisher]

[Guest guest]

Is is possable that these scv's are making people ill like in the

general population making us not that disimilar.I do recover a lot

of staph areus and find it persists in my elbow many years after

therapy.

> > Cool!

> >

> > ==============================

> >

> > FEMS Immunol Med Microbiol. 2005 Jun 14; [Epub ahead of print]

> > Related Articles, Links

> >

> >

> > Identification of antimicrobial compounds active against

> > intracellular Staphylococcus aureus.

> >

> > Malouin F, Brouillette E, ez A, Boyll BJ, Toth JL, Gage

JL,

> > NE.

> >

> > Centre d'Etude et de Valorisation de la Diversite Microbienne

> > (CEVDM), Departement de biologie, Faculte des sciences,

Universite

> > de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., Canada

J1K

> > 2R1.

> >

> > Small-colony variants (SCVs) of Staphylococcus aureus exhibit

> > characteristics of bacteria that can penetrate mammalian cells

and

> > remain intracellular and innocuous for indefinite periods. These

> > properties make SCVs a convenient tool that can be used to

> identify

> > new antibacterial agents having activity against intracellular,

> > quiescent bacteria. Agents active against SCVs could be useful

in

> > the treatment of chronic staphylococcal infections such as

bovine

> > mastitis. An hemB deletion mutant of S. aureus Newbould, a

bovine

> > mastitis isolate, having a stable, genetically defined SCV

> > phenotype, was used in a screening program to identify compounds

> > active against intracellular, gram-positive bacteria. Out of

more

> > than 260,000 compounds screened, nine compounds having the

desired

> > properties were identified. The range of MICs against gram-

> positive

> > bacteria was 0.12-32mugml(-1). One of the compounds (no. 8)

showed

> > excellent activity against gram-positive (MICs 0.12mugml(-1))

and

> > gram-negative (MICs 0.12-4mugml(-1)) bacteria. Each of the nine

> > compounds demonstrated efficacy in a neutropenic mouse thigh

> > infection model. Two compounds, including compound no. 8,

reduced

> > numbers of bacteria in a mouse mastitis model of infection.

> > Application of a stepwise screening process has identified lead

> > compounds that may be useful for treating persistent,

> intracellular

> > infections.

> >

> > PMID: 15963705 [PubMed - as supplied by publisher]