Band 55, Heft 5-6

Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-ᴅ-xylulose 5- phosphate / 2-C-methyl-ᴅ-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since the DOXP/MEP pathway also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis, and in the malaria parasite Plasmodium falciparum, all inhibitors and potential herbicides of the DOXP/MEP pathway in plants are also potential drugs against pathogenic bacteria and the malaria parasite. Plants with their easily to handle DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against pathogenic bacteria and the malaria parasite as no particular security measures are required. In fact, the antibiotic herbicide fosmidomycin specifically inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria and in the parasite P. falciparum, and cures malaria-infected mice. This is the first successful application of a herbicide of the novel isoprenoid pathway as a possible drug against malaria.

Cuticular waxes of Viscum album ssp. album contain oleanolic acid as main constituent, accompanied by aliphatic compounds like alkanes, esters and primary alcohols. A number of flavonol aglycones (methyl ethers of quercetin and kaempferol) have also been identified. Seasonal changes in amount and composition of cuticular waxes and the presence of flavonol aglycones are described and the ecophysiological significance of flavonoids on the surface of the mistletoe is briefly discussed.

The exudate of Ozothamnus hookeri has been investigated for its non-flavonoid constituents. A new natural C 6 -C 3 ester of a long chain fatty acid and seven structurally related kaurane-diterpenoids were isolated. Three of the latter are new natural products, too. A rare 8-methoxy flavonol was also identified.

From a Pseudomonas strain obtained from a soil sample collected in Thailand a pyoverdin was obtained containing twelve amino acids in its peptide chain. The structure elucidation is described.

The structure of a citrate siderophore named achromobactin isolated from the culture medium of Erwinia chrysanthemi was elucidated by spectroscopic methods and chemical degradation.

A new phenylpropanoid glycoside isoangoroside C was isolated from the roots of Scrophularia scorodonia. Its structure was determined on the basis of spectral data as: 3-hydroxy- 4-methoxy-β-phenylethoxy-O-α-ʟ-arabinopyranosyl-(1→6)α ʟ-rhamnopyranosyl-(l→3)-4-O- Z-feruloyl-β-ᴅ -glucopyranoside. Additionally, one known phenylpropanoid, angoroside C, and five known iridoid glycosides, harpagoside, bartsioside, 8-O-acetyl-harpagide, aucuboside and harpagide were isolated and identified.

From leaves of Triticum aestivum a new O-glycosylflavone has been isolated together with chlorogenic acid and its 3′-methyl ether and 6 C-glycosylflavones. The structure of the new flavonoid was determined by 1D and 2D NMR techniques and other spectral evidence as 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone-7-O-β-rutinoside.

Ambrox (1), a perfumery diterpene, was oxidatively metabolised by a plant pathogenic fungus Botrytis cinerea in a xenobiotic fashion to afford a major product, i.e., 1β-hydroxy-8- epiambrox (13) (60% ) along with three minor metabolites 3β-hydroxyambrox (2), sclareolide (5) and 3β-hydroxysclareolide (7). Sclareolide (5), a cytotoxic diterpenoidal lactone was fermented with the same fungus to yield 3β-hydroxysclareolide (7) (59% ) as a major metabolite together with two minor metabolites characterised as 1-ketosclareolide (15), and 3β,14-dihydroxysclareolide (16).

The interaction between azurin from Pseudomonas aeruginosa and Ag(I), Cu(II), Hg(II), was investigated as a function of protein state, i.e. apo-, reduced and oxidised azurin. Two different metal binding sites, characterized by two different spectroscopic absorbancies, were detected: one is accessible to Ag(I) and Cu(II) but not to Hg(II); the other one binds Ag(I) and Hg(II) but not copper. When added in stoichiometric amount, Ag(I) shows high affinity for the redox center of apo-azurin, to which it probably binds by the -SH group of Cys112; it can displace Cu(I) from reducedazurin, while it does not bind to the redox center of oxidizedazurin. Kinetic experiments show that Ag(I) binding to the reducedform is four times faster than binding to the apo-form. This result suggests that metal binding requires a conformational rearrangement of the active site of the azurin. Interaction of A g(I) or Hg(II) ions to the second metal binding site, induces typical changes of UV spectrum and quenching of fluorescence emission.

Temperature - induced changes in protein intrinsic fluorescence of native, delipidated and deionized purple membranes are investigated. It is found that the removal of cations most strongly affects the protein and its thermal stability. The denaturation of dei-BR completes at 70 °C, while delipidated and native BR still maintain their native structure at this temperature. Both, the quantum yield and the fluorescence maximum suggest correlation between the Trp-retinal coupling and protein structural stability. The low red shift of the fluorescence maximum caused by increasing of temperature indicates limited unfolding of bacteriorhodopsin upon denaturation.

Glycolate oxidase that was partially purified from pea leaves was inactivated in vitro by blue light in the presence of FMN. Inactivation was greatly retarded in the absence of O 2 . Under aerobic conditions H 2 O 2 was formed. The presence of catalase, GSH or dithiothreitol protected glycolate oxidase against photoinactivation. Less efficient protection was provided by ascorbate, histidine, tryptophan or EDTA. The presence of superoxide dismutase or of hydroxyl radical scavengers had no, or only minor, effects. Glutathione suppressed H 2 O 2 accumulation and was oxidized in the presence of glycolate oxidase in blue light. Glycolate oxidase was also inactivated in the presence of a superoxide-generating system or by H 2 O 2 in darkness. In intact leaves photoinactivation of glycolate oxidase was not observed. However, when catalase was inactivated by the application of 3-amino-1,2,4-triazole or depleted by prolonged exposure to cycloheximide a strong photoinactivation of glycolate oxidase was also seen in leaves. In vivo blue and red light were similarly effective. Furthermore, glycolate oxidase was photoinactivated in leaves when the endogenous GSH was depleted by the application of buthionine sulfoximine. Both catalase and antioxidants, in particular GSH, appear to be essential for the protection of glycolate oxidase in the peroxisomes in vivo.

Potato tuber disks, when treated with laminarin, a β-1,3-glucooligosaccharide from Laminaria digitata, accumulate a hydroxycinnamoyl amide compound, N-p-coumaroyloctopamine (p-CO). The biosynthesis of p -CO was investigated by feeding experiments, in order to show that the precursors of N-p-coumaroyl and octopamine moieties of p-CO are ʟ-phenylalanine and ʟ-tyrosine, respectively. The treatment of potato tuber tissue with laminarin resulted in elevated activities of four enzymes which are putatively involved in p-CO biosynthesis: phenylalanine ammonia lyase (PAL; EC 4.3.1.5), 4-hydroxycinnamic acid:CoA ligase (4CL; EC 6.2.1.12), hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) and tyrosine decarboxylase (TyrDC; EC 4.1.1.25). Among these, the response of TyrDC was specific to laminarin treatment, thus indicating that the regulation of TyrDC activity is critical for the accumulation of p -CO in potato tuber tissue.

Capacities of phosphoenolpyruvate carboxylase (PEP-Co), ribulose bisphosphate carboxylase (Rubisco), NADP + malic enzyme (ME) and of malate dehydrogenase (MDH) were measured in the Euphorbiacea Aleurites montana, grown under 700 ppm CO 2 for four weeks prior to enzyme extraction. For comparison Bryophyllum daigremontiana (CAM), Saccharum officinarum (C 4 ) and Capsicum frutescens (C 3 ) were treated in the same way. PEP-Co capacity of Aleurites was in the range of 12-, that of Capsicum approx. 26 nmol × min -1 × mg protein -1 , without significant influence of the light period or CO 2 -treatment. In contrast, the activity of the enzyme from Saccharum was. depending on the duration of light, 160- respectively 96 times higher than that of the tung-oil tree. In Bryophyllum a rather low activity in the morning was increased during the day to approx. 230 nmol × min -1 × mg protein -1 in plants grown in the greenhouse and to approx. 115 nmol × min -1 × mg protein -1 in those from the growth chamber. Malate was hardly detectable in extracts of Aleurites, whereas it was high in Bryophyllum, depending on the light period. The ratio of average PEP-Co to Rub-Co capacity was high for the CAM-plant (20:1), somewhat lower for sugar cane (10:1), but almost at equality for Aleurites (0.9:1) and chilli (0.8:1). For the NADP + malic enzyme, low capacity (20 to 28 nmol x min -1 × mg protein -1 ) was found for Aleurites and for Capsicum, whereas it was 10 to 17 times higher in Saccharum. In Bryophyllum, the activity was up to 80 nmol × min -1 × mg protein , dependent on light period. MDH capacity was extremely high in all plants investigated. Highest rates (10-20 μmol × min -1 × mg protein -1 ), were obtained for Bryophyllum, followed by sugar cane and Capsicum with 5 -8 μmol × min-1 x mg protein-1. Again, the lowest capacity was found in extracts of Aleurites with approx. 1.3 to 1.6 μmol × min -1 × m protein -1 . Thus, in Aleurites montana no indication for C 4 - or Crassulacean acid metabolism was obtained. Therefore, the earlier observed very efficient uptake of CO 2 cannot be explained by a high expression of the PEP-Co protein, known to occur in CAM- and C 4 - plants.

We show that urea inhibits the ATPase activity of MgATP submitochondrial particles (MgATP-SMP) with Ki = 0.7 м, probably as a result of direct interaction with the structure of F 0 F 1 -ATPase. Counteracting compounds (sorbitol, mannitol or inositol), despite slightly (10-20% ) inhibiting the ATPase activity, also protect the F 0 F 1 ATPase against denaturation by urea. However, this protection was only observed at low urea concentrations (less than 1.5 м ) , and in the presence of three polyols, the K i for urea shift from 0.7 м to 1.2 м. Urea also increases the initial activation rate of latent MgATP-SMP in a dose-dependent-manner. However, when the particles (0.5 mg/ml) were preincubated in the presence of 1 м , 2 м or 3 м urea, a decrease in the activation level occurred after 1 h, 30 and 10 min, respectively. At high MgATP-SMP concentration (3 mg/ml) a decrease in activation was observed after 2 h, 1 h and 20 min, respectively. These data indicate that the effect of urea on the activation of MgATP-SMP depends on time, urea and protein concentrations. It was also observed that polyols suppress the activation of latent MgATP-SMP in a dose-dependent manner, and protect the particles against urea denaturation during activation. We suppose that a decrease in membrane mobility promoted by interactions of polyols with phospholipids around the F 0 F 1 ATPase may also increase the compactation of protein structure, explaining the inhibition of natural inhibitor protein of ATPase (IF 1 ) release and the activation of the enzyme.

Fifteen Rosa cultivated races were described by means of phenotypic frequencies (11 tables). Two groups of correlated contingency tables were identified by ACT-STATIS (Analyse Conjointe de Tableaux - Structuration de Tableaux à Trois Indices de la Statistique) interstructure analysis. Three data sets appeared to be independent from the others. Typologies of races were obtained after ACT-STATIS compromise analyses for the two groups of correlated tables, and after Principal Component Analyses for the independent data sets. Each typology was original and variously influenced by genealogical structure, mutation or artificial selection pressures. A weighted synthesis was attempted in order to build a taxonomy of races taking into account these diversity factors. The good agreement between the resulting classification and the assumptions about the history of Rosa domestication advocated for a wider utilization of ACT-STATIS and RV coefficient when the relationships between individuals or populations have to be studied on the basis of their similarities.

In this paper we show a microcalorimetric investigation carried out on the so-called cores, i. e. ribosomes deprived of select proteins by LiCl treatment. Thermal degradation of native ribosomes gives rise to two thermal transitions occurring at different temperatures. In the cores the high temperature peak persists even after treatment at very high ion strength (2 м LiCl). This strongly suggests the existence of a very stable structure that was previously observed also in particles treated with agents that hydrolyze the RNA moiety. The low temperature peak gradually but dramatically decreases even though it never disappears completely This indicates that the treatment to obtain ribosomal cores does not cause complete unfolding of the particle but only the destabilization of a structural three-dimensional domain present in native ribosomes. These data are discussed in the light of previous results obtained by dielectric spectroscopy and microcalorimetric studies on ribosomal particles.

The micellization process of dodecyltrimethylammonium chloride (DTAC) and bromide (DTAB) was studied. Nuclear magnetic resonance method was used. The 1 H NM R and 13 C NM R spectra were taken at higher and lower concentrations than the critical micelle concentrations (CMC) of the compounds studied. Chemical shifts were analysed. The studies performed were prompted by earlier calorimetric measurements which showed that there were significant qualitative and quantitative differences in the micellization process of the compounds studied. Namely, DTAB micelle dissociation was found to be an endothermic process while that of DTAC was exothermic. The differences found must be the result of differentiated influence of bromide and chloride counterions on the micellization process, including the phenomenon of micelle hydration. The objective of the work was to check whether cationic surfactant counterions can influence the micelle hydration process. Indeed, DTAB and DTAC, as monomers, exhibit similar hydrophobic hydration, but DTAB micelles are more hydrated than DTAC ones. It seems that the differences found in micellization of both salts studied may be attributed to different physicochemical properties of bromide and chloride ions, such as their mobilities and radii of their hydrated forms. Moreover, the effect of anions on the water structure must be taken into account. It is important whether the anions can be classified as water ordering kosmotropes, that hold the first hydration shell tightly, or water disordering chaotropes, that hold water molecules in that shell loosely.

Fluorescein-PE is a fluorescence probe that is used as a membrane label or a sensor of surface associated processes. Fluorescein-PE fluorescence intensity depends not only on bulk pH, but also on the local electrostatic potential, which affects the local membrane interface proton concentration. The pH sensitivity and hydrophilic character of the fluorescein moiety was used to detect conformational changes at the lipid bilayer surface. When located in the dipalmitoylphosphatidylcholine (DPPC) bilayer, probe fluorescence depends on conformational changes that occur during phase transitions. Relative fluorescence intensity changes more at pretransition than at the main phase transition temperature, indicating that interface conformation affects the condition in the vicinity of the membrane. Local electrostatic potential depends on surface charge density, the local dielectric constant, salt concentration and water organisation. Initial increase in fluorescence intensity at temperatures preceding that of pretransition can be explained by the decreased value of the dielectric constant in the lipid polar headgroups region related in turn to decreased water organisation within the membrane interface. The abrupt decrease in fluorescence intensity at temperatures between 25 °C and 35 °C (DPPC pretransition) is likely to be caused by an increased value of the electrostatic potential, induced by an elevated value of the dielectric constant within the phosphate group region. Further increase in the fluorescence intensity at temperatures above that of the gel-liquid phase transition correlates with the calculated decreased surface electrostatic potential. Above the main phase transition temperature, fluorescence intensity increase at a salt concentration of 140 m M is larger than with 14 m M . This results from a sharp decline of the electrostatic potential induced by the phosphocholine dipole as a function of distance from the membrane surface.

Three new prostaglandins were isolated as minor constituents of the organic extract from the Caribbean soft coral Plexaura nina. The structures of the new natural products w ere established by means of spectral data analysis, including 2D NMR experiments. The unpalatability of the lipid extract of the coral and the defensive role of the major prostaglandin metabolites were determined by laboratory and field fish-feeding assays.

The chemical composition of the investigated gorgonians showed a high level of individual variation and the colonies, according to their major contributors, were assigned to 10 distinct chemical profiles, among which A , C, E , and G were them ost abundant ones. From the metabolites identified in the present study, either by means of GC /MS or using NMR techniques after conventional separation procedures, the novel cyclic ether 5,10-epoxymuurolane is found in significant quantities in D and I chemical profiles. Furanotriene, isofuranotriene and furanodiene could be referred as the most common metabolites of the genus, since they are found in 6 out of 10 chemical profiles. Isosericenine is, also, a significant contributor of H and I chemical profiles. A number of sesquiterpene hydrocarbons, such as curzerene, bicyclogermacrene, valencene, β-bourbonene and β -elemene, along with the oxygenated sesquiterpenes elemanolide and furoventalene, are present at varying concentrations in the majority of the chemical profiles. Metabolites of high discriminant value are: α-himachalene for the K chemical profile, α -santalene and its oxygenated derivatives for the G chemical profile and the three geometrical isomers of germacrone for the F chemical profile. Several chemical profiles show ed narrow geographic distribution. Most of the chemical profiles are located in the north, while F inhabits mainly southern sites and the others are equally distributed. Finally, 91 % of the chemical profiles of the gorgonian colonies appeared to grow in all depths, while 9 % did not inhabit deep -water environments. Most chemical profiles are less frequent at higher water depths with the exception of chemical profiles A and C.

The bushhopper Phymateus leprosus (Fabricius) in the field shows a special appetite for the milkweed Asclepias fruticosa. Asclepiadaceae, like Apocynaceae and Scrophulariaceae, contain cardiac glycosides. Raw and purified extracts of these plants phagostimulate larval and adult P. leprosus. We also screened natural and half-synthetic compounds found in those plant extracts. While saponins and sapogenins did not stimulate the animals, many cardiac glycosides and aglycones, offered on filter paper, proved to be phagostimulants.

The transcriptional expression of an ischemia responsive protein (irp94) in the hippocampus of rats was analyzed by Northern blotting. A transient forebrain ischemia was induced in the rats by temporary occluding of the bilateral common carotid arteries (CCAs) for various periods, and then reperfusion. Among the frontal, parietal, temporal and occipital lobes, and the cerebellum and hippocampus, the maximum mRNA expression of irp94 was at the occipital lobe, and the minimum was at the parietal lobe following ten min of forebrain ischemia. The irp94 mRNA expression reached a maximum fifteen min after the transient ischemia. From twenty min on after the ischemia its expression decreased. After a ten-min ischemia and the following reperfusion, irp94 mRNA expression gradually increased in the first twelveh, and then decreased. The expression pattern was like that of the endoplasmic reticulum chaperone, Erp72, but not that of the cytosol chaperone, hsp72. In addition, when intracellular ATP was depleted with antimycin A the mRNA level of irp94 increased in a thyrocyte cell culture model. The results suggest that irp94, like a molecular chaperone, may play a role in protecting the cell against external stimulation, especially after a transient forebrain ischemia. Although future studies of irp94 will be required to clarify the interactions with other intracellular factors inducing ischemia or showing molecular chaperone activity, what is offered here is an insight into its functional role as a component of stress response in neurons that should be considered as a new therapeutic approach for the treatment of ischemia.

Leptin concentrations in the interscapular brown adipose tissue (IBAT) of the common shrew (Sorex araneus) were measured in different seasons. The leptin concentrations in IBAT were much higher than in the liver, where leptin is supposed to be of blood origin. In the heart muscle no detectable amount of leptin was found. There were clear seasonal variations in the leptin concentrations in IBAT. Leptin levels in IBAT were the lowest in November at the beginning of the winter. The concentrations increased, however, strongly after the onset of the permanent snow cover, and the highest concentrations were measured in December- January, when the weight of the animals was very low. In April-May, at the time when shrews attain sexual maturity, leptin concentrations in IBAT were lower than in the mid-winter, but significantly higher than in November. In overwintered adults the leptin concentrations were at the same level as in nonwintered subadults. Leptin originating from BAT may inform the central nervous system about the amount of nonshivering thermogenesis as well as the amount of feeding necessary for survival in the winter months.

Drugs which exert their effects by interacting with DNA cause structural and functional membrane alterations which may be essential for growth inhibition by these agents. This paper describes the interaction of cisplatin with the human erythrocyte membrane and models constituted by bilayers of dimyristoylphosphatidylethanolamine (DMPE) and diacylphosphatidylserine (DAPS), representative of phospholipid classes located in the inner monolayer of the erythrocyte membrane, and of dimyristoylphosphatidylcholine (DMPC), a class present in its outer monolayer. Cisplatin ability to perturb DMPE, DAPS and DMPC bilayer structures was determined by X-ray diffraction and fluorescence spectroscopy. Electron microscopy disclosed that human erythrocytes incubated with 35 μм cisplatin, which is its therapeutical concentration in serum, developed cup-shaped forms (stomatocytes). According to the bilayer couple hypothesis, this means that the drug is inserted into the inner monolayer of the erythrocyte membrane, a conclusion supported by the studies on model systems.

A series of hydrolysable tannins and related compounds was evaluated for antifungal activities against filamentous fungi ( Epidermophyton floccosum; Microsporum canis; Microsporum gypseum: Trichophyton mentagrophytes; Trichophyton rubrum; Trichophyton tonsurans; Trichophyton terrestre; Penicillium italicum; Aspergillus fumigatus; Mucor racemosus; Rhizopus nigricans) and opportunistic yeasts ( Candida albicans; Candida glabrata; Candidata krusei; Cryptococcus neoformans), using the agar dilution method. While all samples had no activity against the filamentous fungi in concentrations of 1.1 -5.9 μм (1000 [μg/ml), the phenolic compounds displayed significant potencies against all the opportunistic yeasts tested but C. albicans, with minimum inhibitory concentrations ranging from 0.02 to 0.1 μм ( 16 - 125 (μg/ml). Although the presence of galloyl groups in flavonoids did not necessarily produce activity, this structural element, an HHDP moiety or its oxidatively modified entity proved to be an important structural feature of hydrolysable tannins. Comparison of dilution methods provided strong evidence of dependence of MIC values on the test method. Employing the microdilution broth method, the ellagitannin corilagin (MIC 0.8 nм) was found to be similarly potentially active as amphotericin B (MIC 0.5 nм) and sertaconazole (MIC 0.9 nм) against Candida glabrata strains. The order of effectiveness observed being 64- and 4 -8-fold increased for corilagin and the reference compounds respectively, when compared with that of the agar dilution test.

Contrary to Leishmania spp. and Trypanosoma cruzi, Trypanosoma brucei bloodstream forms do not synthesise their own sterols but take these compounds in the form of cholesterol directly from the mammalian host. However, procyclic insect stages synthesise ergosterol rather than cholesterol. Here the sub-cellular localisation of the first committed enzyme of this pathway of isoprenoid synthesis 3-hydroxy-3-methylglutaryl-coenzyme A reductase in T. brucei procyclics (0.9 nmol. min -1 . mg -1 protein) was carried out using both cell-fractionation by isopycnic centrifugation and digitonin-titration experiments. The majority of the NADP + - linked 3-hydroxy-3-methylglutaryl-coenzyme A reductase is a soluble enzyme present in the mitochondrial matrix with some additional membrane-associated activity in glycosomes and possibly in the endoplasmic reticulum. It is suggested that the active metabolism of threonine and/or leucine as preferred 2-carbon source for the incorporation of acetyl units into lipids and/or sterols in the mitochondrion of T. brucei procyclics is the explanation for a high 3- hydroxy-3-methylglutaryl-coenzyme A reductase activity in these protozoan organelles.

We have isolated two phytoconstituents present in the B. forficata leaves, a medicinal plant employed in folk medicine specially for the treatment of diabetes. These compounds were isolated by column chromatography and identified as β-sitosterol and kaempferol-3,7-dirhamnoside (kaempferitrin) by spectroscopical data and comparison with authentic samples. A comparative study with different parts of the plant indicated that the latter is present only in the leaves, suggesting that it might be useful for a suitable quality control of phytotherapeutics which contain this organ of B. forficata in its composition.

From the acetone extract of the North American toadstool Lepiota americana 2-aminophenoxazin-3-one (1) and a novel amino-1,4-benzoquinone derivative, lepiotaquinone (2), were isolated. The structure of 2 was confirmed by its preparation from 2-aminophenol and amino-1,4-benzoquinone.

From a methanol extract of dried-ground aerial parts of Senecio lyratus, an anti-fungal and anti-bacterial active compound was isolated and identified as β-sitosterol by spectroscopic analysis.

A total of 635 clinically diagnosed typhoid fever patients were bled from three different health institutions in the metropolis of Lagos, Nigeria over a period of 15 months, May 1997 to July 1998. Out of the total blood cultured, 101 (15.9% ) isolates of Salmonella species were isolated of which 68 (67.3% ) were S. typhi, 17 (16.8% ) and 16 (15.8% ) were S. paratyphi A and S. arizonae respectively. The overall isolation rate of S. typhi among patients is 10.7% , with most isolates 45.9% found among the severely-ill young adults, age group 1 6 -30 years. All isolates were subjected to anti-microbial susceptibility testing using 12 different antibiotics: chloramphenicol, ampicillin, cotrimoxazole, gentamicin, colistin sulfate, nalidixic acid, nitrofurantoin, cefotaxime, tetracycline, streptomycin, ofloxacin and ciprofloxacin. All the S. typhi and S. paratyphi A isolates showed resistance to two or more of the 10 of 12 antibiotics tested particularly the 3-first-line antibiotics commonly used (chloramphenicol, ampicillin and cotrim oxazole) in the treatment of typhoid fever in Nigeria. No isolate showed resistance to ofloxacin and ciprofloxacin, however, nalidixic acid and gentamicin showed a moderate and appreciable inhibition to most of our isolates.