Fatty acids bacterial inhibition

Fiber components are the principal energy source for colonic bacteria with a further contribution from digestive tract mucosal polysaccharides. Rate of fermentation varies with the chemical nature of the fiber components. Short-chain fatty acids generated by bacterial action are partiaUy absorbed through the colon waU and provide a supplementary energy source to the host. Therefore, dietary fiber is partiaUy caloric. The short-chain fatty acids also promote reabsorption of sodium and water from the colon and stimulate colonic blood flow and pancreatic secretions. Butyrate has added health benefits. Butyric acid is the preferred energy source for the colonocytes and has been shown to promote normal colonic epitheUal ceU differentiation. Butyric acid may inhibit colonic polyps and tumors. The relationships of intestinal microflora to health and disease have been reviewed (10). 

Systemic antibiotics are indicated for moderate-severe inflammatory acne not responding to topical treatments. Systemic antibiotics act on 1) suppression of P. acnes growth 2) inhibition of bacterial lipases 3) reduction of free fatty acids and 4) reduction of inflammation. Oxytetracycline and its derivatives are the most commonly used oral antibiotics. Second-generation tetracyclines such as minocycline, doxy-cycline and lymecycline present longer half-lives, enhanced bacterial activity and lower... 

Significant work continues by both the academic groups and the pharmaceutical industry to validate the FASH targets and discover relevant inhibitors. A selection of some efforts to inhibit bacterial fatty acid biosynthesis at various stages is presented in this chapter. 

Mecftantsm of Action A lincosamide antibacterial that inhibits protein synthesis of the bacterial cell wall by binding to bacterial ribosomal receptor sites. Topically, it decreases fatty acid concentration on the skin. Therapeutic Effect Bacteriostatic. Prevents outbreaks of acne vulgaris. 

RJ Heath, JR Rubin, DR Holland, E Zhang, ME Snow, CO Rock. Mechanism of triclosan inhibition of bacterial fatty acid synthesis. JBiol Chem 274 11110-11114, 1999. 

G-protein a-subunits also possess specific residues that can be covalently modified by bacterial toxins. Cholera toxin catalyzes the transfer of ADP-ribose moiety of NAD to a specific arginine residue in certain a-subunits, whereas pertussis toxin ADP-ribosylates those a-subunits that contain a specific cysteine residue near the carboxy-terminus. Modification of the a-subunit by cholera toxin persistently activates these protein by inhibiting their GTPase activity, whereas pertussis toxin inactives Gia protein and thereby results in the uncoupling of receptor from the effector. G-protein a-subunits are regulated by covalent modifications by fatty acids myristate and palmate. These lipid modifications serve to anchor the subunits to the membrane and increase the interaction with other protein and also increase the affinity of the a-subunit for 3y. In this regard, the myristoylation of Gia is required for adenylyl cyclase inhibition in cell-free assay (Taussig et al. 1993). 

It is not surprising that fatty acids inhibit COX and LOX enzymes due to their structural similarities with arachidonic acid. A supercritical fluid extract from the fruits of Sabal serrulata (also called Serenoa repens Small. Arecaceae) has been utilized for the treatment of benign prostatic hyperplasia (BPH) and non-bacterial prostatitis. The extract was demonstrated as a dual inhibitor of COX and 5-LOX pathways with IC50 at 28.1 pg/ml and 18.0 (ig/ml, respectively. A further evaluation of the supercritical carbon dioxide extract showed the acidic lipophilic fraction, most likely fatty acids, had the same dual inhibitory activities as the parent extract [121]. 

Because cholesterol contains an -OH group, it is amphipathic. It controls membrane fluidity in mammals by inhibiting the ordering of fatty acid side chains, but it is absent from bacterial plasma membranes. 

Patynowski et al. (2002) showed that yeasts produce an unidentified inhibitory factor (maybe a toxic metabolite) that could be responsible for the inhibition of bacterial growth. These results could explain the antagonism between yeasts and malolactic bacteria, since yeasts are known to produce compounds during alcoholic fermentation such as ethanol, SO2, medium-chain fatty acids and antibacterial proteins/peptides (Weeks et al. 1969 De Oliva et al. 2004 Comitini et al. 2005 Osborne and Edwards 2007). The nature and quantity of peptides and other molecules released by yeasts are different depending on winemaking techniques and the yeast strain. 

The enolic thiofuranone derivatives 35 (e.g. R = n-propyl and R = n-decyl) and 36 are also inhibitors of fatty acid synthase and have served as drug leads against Plasmodium falciparum (malaria) and Trypanosoma (sleeping sickness) . Several tetronic acid derivatives exhibit significant inhibition toward bacterial peptidoglycan synthesis (K = 0.19 p.M for the derivative R = 2-naphthalene and (R, R ) = vinyl-1-naphthalene in equation 8 analogous to 39) . ... 

Zhang Y-M, White SW, Rock CO. Inhibiting bacterial fatty acid 24. synthesis. J. Biol. Chem. 2006 281 17541-17544. 

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