Anti-Pasteurella pestisFactor III. Effects of Fatty Acids onPasteurella pestis

Abstract

The bactericidal activity and the chemical and physical characteristics of lipid fractions of extracts from organs of normal mice and guinea pigs have been described previously. The present study describes the effects of commercially prepared fatty acids which are representative of those found in the extracts. Saturated fatty acids with 12, 14, and 16 carbon atoms and unsaturated fatty acids with more than one double bond were the most effective in killing Pasteurella pestis. Tweens 20 and 80, Spans 40 and 80, and some of the methyl esters of the fatty acids did not strongly inhibit P. pestis. It was concluded, therefore, that both the length of the carbon chain and the presence of the carboxyl group of the free fatty acids were important in their effects on P. pestis. Neither the very active lauric acid nor the relatively inactive oleic acid appeared to severely alter the morphology of P. pestis. Supernatant fluids from incubated mixtures of sodium laurate or sodium oleate and cells did not contain significantly greater concentrations of proteins or nucleic acids than did the controls. These observations do not preclude an alteration of the permeability of the cell walls. An anti-Pasteurella pestis factor (APF) prepared from the organs of normal animals (3) proved to be a lipoprotein (2). Its antibacterial activity in vitro was ascribed to the lipid fraction which was held in solution by the protein. The lipid was separable by extraction with chloroform, and the component fatty acids of this antibacterial fraction were identified. The present report describes the antibacterial activities of commercial fatty acids representing those found in greatest concentrations in APF from mouse liver. MATERIALS AND METHODS Fatty acids and derivatives. Caproic, caprylic, lauric, myristic, palmitic, stearic, and linoleic acids were obtained from Matheson, Coleman, and Bell, Norwood, Ohio. Oleic acid was obtained from Braun-Knecht-Heiman Co., San Francisco, Calif. Linolenic acid and the methyl esters of lauric, myristic, palmitic, and linoleic acids were obtained from Nutritional Biochemicals Corp., Cleveland, Ohio. Tween 20 (polyoxyethylene sorbitan monolaurate), Tween 80 (sorbitan mono-oleate, polyoxyalkalene derivative), Span 40 (sorbitan monopalmitate), and Span 80 (sorbitan mono-oleate) were manufactured by Atlas Chemical Industries, Inc., Wilmington, Del.

Possible Mechanisms of Action of an Anti-Pasteurella pestisFactor

“…Our data show that fatty acids characteristic of APF inhibited the oxidation of 6-PG and G-6-P but not of 8-D-G. The saturated fatty acids most active against P. pestis, namely, lauric, myristic, and palmitic (8), were also the most inhibitory, along with oleic and linoleic acids, for the enzyme systems. On the other hand, APF inhibited both ,B-D-G and 6-PG systems but did not inhibit the oxidation of G-6-P. No explanation is offered for these differences in activities of APF and fatty acids.…”

“…Ultraviolet absorption spectra were obtained with a Beckman DK-1 spectrophotometer. The concentrations of nucleic acids and proteins were calculated with absorbances at 260 and 280 nm as described previously (8). The deoxyribonucleic acid (DNA) was also determined chemically (4,25).…”

Characterization of a bactericidal lipid developing within staphylococcal abscesses

“…The antimicrobial activities offatty acids from tissues of both normal and infected animals have been reported by several investigators (7)(8)(9)(18)(19)(20). The antibacterial activity of a fatty acid is dependent upon both the fatty acid structure and the bacterial species involved (24).…”

“…Gram-positive bacteria are also more sensitive to unsaturated fatty acids (3,15,21,24). Stereochemical configuration (3,15,24), position of unsaturation (15), presence of a free carboxyl group (3,9,21), and oxidation or peroxidation of double bonds (14,27,28) are other important determinants affecting the antimicrobial activity of long-chain unsaturated fatty acids.…”

Constitutive uptake and degradation of fatty acids by Yersinia pestis

“…Accordingly, the killing of bacteria by fatty acids has been proposed as a host defense mechanism (7,16). Fatty acids were identified as an anti-Yersinia pestis factor found in mice and guinea pigs, with C-16 fatty acids having the greatest antibacterial effects (5). However, it is difficult to reconcile the reported fatty acid sensitivity of Y. pestis with the known ability of this bacterium to survive and multiply in the fatty acid-rich environment provided by the mammalian host.…”