scholarly journals Study of the Effect of Carob (Ceratoniasiliqua L.) Extract Activity as Antibiotic from UTI

2018 ◽  
Vol 8 (1) ◽  
pp. 17-25
Author(s):  
Iman Fadhil Abdul-Husin
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Plant Extracts ◽  
Ethanol Extract ◽  
Species Level ◽  
Bacterial Cells ◽  
E Coli ◽  
In Vitro Antibacterial Activity ◽  
Resistant Strains

Escherichia coli  bacterial cells have been collected and selected from(30) patients (most found strain) in urine samples 25 (83.3 %) suffering from infection of urinary tract laid down in Hashimiyaha teaching hospital, Babylon during a period from Novembertwo thousand sixty to February two thousand seventy. The isolated strain  diagnosis is confirmed withVitek2 system apparatus which performed to identify species level ofEscherichia coli  isolates.To evaluate the antimicrobialaction of the ethanol extract of  Carob (CeratoniasiliquaL.) podsonlyas well as in mixture with certain drugs (64µg /ml ampicillin, 32µg /ml gentamicin, 128µg /ml amikacin,8µg /ml clindamycin.) as the wide usageantibiotics in the treatment of UTI bacterial infectionswhich has led to the emergence and spread of resistant strains. Many studies showed that the efficacy of antimicrobials can be improved by combining them with crude plant extracts. The antimicrobial activity of the ethanol extract of pods of Carob(CeratoniasiliquaL.)alone as well as in mixture with some  standard antimicrobials has been evaluated using well diffusion methodwhich demonstrates an in-vitro antibacterial activity of the tested extracts against E. Coli bacteria.  A combination of the tested extracts( concentration 100%,50%) with antibacterial has increased that activity of the tested antimicrobials.The results revealed the importance of  Carob plant extracts when associated with antibiotics to regulatorresistance E. Coli bacteria that developed as adanger to human health

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

In Vitro Antibacterial activity of ethanolic extract of Myrsine africana against laboratory Strains of Pathogenic Organisms

2016 ◽  
Vol 5 (04) ◽  
pp. 4512
Author(s):  
Jackie K. Obey ◽  
Anthoney Swamy T* ◽  
Lasiti Timothy ◽  
Makani Rachel
Keyword(s):  
Antibacterial Activity ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
E Coli ◽  
Zones Of Inhibition ◽  
In Vitro Antibacterial Activity ◽  
Myrsine Africana

The determination of the antibacterial activity (zone of inhibition) and minimum inhibitory concentration of medicinal plants a crucial step in drug development. In this study, the antibacterial activity and minimum inhibitory concentration of the ethanol extract of Myrsine africana were determined for Escherichia coli, Bacillus cereus, Staphylococcus epidermidis and Streptococcus pneumoniae. The zones of inhibition (mm±S.E) of 500mg/ml of M. africana ethanol extract were 22.00± 0.00 for E. coli,20.33 ±0.33 for B. cereus,25.00± 0.00 for S. epidermidis and 18. 17±0.17 for S. pneumoniae. The minimum inhibitory concentration(MIC) is the minimum dose required to inhibit growth a microorganism. Upon further double dilution of the 500mg/ml of M. africana extract, MIC was obtained for each organism. The MIC for E. coli, B. cereus, S. epidermidis and S. pneumoniae were 7.81mg/ml, 7.81mg/ml, 15.63mg/ml and 15.63mg/ml respectively. Crude extracts are considered active when they inhibit microorganisms with zones of inhibition of 8mm and above. Therefore, this study has shown that the ethanol extract of M. africana can control the growth of the four organisms tested.

scholarly journals Evaluation du potentiel antimicrobien et de la toxicité des extraits de Jatropha multifida Linn, (Euphorbiaceae)

2020 ◽  
Vol 151 ◽  
pp. 15550-15558
Author(s):  
Amégninou Agban ◽  
Yao Hoekou ◽  
Passimna Pissang ◽  
Tchadjobo Tchacondo ◽  
Komlan Batawila
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Aqueous Extract ◽  
E Coli ◽  
Toxicological Studies ◽  
Jatropha Multifida

Objectif : L’objectif de ce travail était d’évaluer in vitro l’activité antimicrobienne des extraits de feuilles et tige de Jatropha multifida sur la croissance de Candida albicans, Escherichia coli et Staphylococcus aureus, puis d’évaluer in vivo la toxicité de cette plante. Méthodologie et résultats : Les méthodes de diffusion en milieu gélosé et de microdilution en milieu liquide ont été utilisées pour évaluer l’effet antimicrobien. Une étude en subaigüe était réalisée afin d’explorer les effets toxiques de l’extrait aqueux des feuilles. Les résultats des tests antimicrobiens montrent une activité des extraits de feuilles et tige de J. multifida sur la croissance des souches utilisées avec des diamètres de zones d’inhibition allant de 8 à 25 mm et des concentrations minimales inhibitrices (CMI) variant de 0,039 mg/mL à 1,25 mg/mL à l’exception des souches de E. coli qui sont résistantes aux extraits de la tige. L’administration en subaigüe de l’extrait aqueux des feuilles de J. multifida à la dose de 600 mg/kg entraîne une perte significative de poids chez les souris. Conclusion et applications des résultats : Les extraits aqueux, éthanolique et hydroéthanolique des feuilles et tige de J. multifida possèdent d’activité antimicrobienne et pourraient être utilisés dans le traitement des Candidoses à C. albicans et des infections à S. aureus. Mais l’essai de toxicité subaigüe montre que l’extrait aqueux de la plante serait toxique. Des études toxicologiques approfondies restent donc nécessaires sur ces extraits afin de mieux élucider leur inocuité. Mots-clés : Jatropha multifida, extraits de feuilles et de tige, activités antifongique et antibactérienne, toxicité. Agban et al., J. Appl. Biosci. 2020 Evaluation du potentiel antimicrobien et de la toxicité des extraits de Jatropha multifida Linn, (Euphorbiaceae) 15551 Evaluation of antimicrobial potential and toxicity of Jatropha multifida Linn, (Euphorbiaceae) extracts ABSTRACT Objective: The objective of this study was to evaluate in vitro the antimicrobial activity of leaves and stem of Jatropha multifida extracts against Candida albicans, Escherichia coli and Staphylococcus aureus, and then to evaluate in vivo the toxicity of this plant. Methodology and Results: The agar well-diffusion and the NCCLS broth microdilution methods were used to assess the antimicrobial effect. A subacute study was carried out to explore the toxic effects of the aqueous extract of the leaves. The results of the antimicrobial tests show an activity of the extracts of leaves and stems of J. multifida on the growth of the strains used with diameters of inhibitory zones ranging from 8 to 25 mm and minimum inhibitory concentrations (MIC) varying from 0.039 mg/mL to 1.25 mg/mL exception E. coli strains which are resistant to extracts from the stem. Subacute administration of the aqueous extract of the leaves of J. multifida at a dose of 600 mg/kg leads to a significant loss of weight in the mice. Conclusion and application of findings : The aqueous, ethanolic and hydroethanolic extracts of the leaves and stem of J. multifida have antimicrobial activity and could be used in the treatment of Candidiasis and bacterial infections due respectively to C. albicans and S. aureus. But the subacute toxicity test shows that the aqueous extract of the plant would be toxic. Extensive toxicological studies therefore remain necessary on these extracts in order to better elucidate their safety. Keywords: Jatropha multifida extracts of leaves and stem, antifungal and antibacterial activities, toxicity

scholarly journals In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 267 ◽  
Author(s):  
Le Phuong Nguyen ◽  
Naina Adren Pinto ◽  
Thao Nguyen Vu ◽  
Hyunsook Lee ◽  
Young Lag Cho ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
Intrinsic Activity ◽  
In Vitro Activity ◽  
E Coli ◽  
Acinetobacter Spp ◽  
Resistant Strains ◽  
Lactamase Inhibitor

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains.

scholarly journals (E)-N′-(4-Fluorobenzylidene)-5-methyl-2-(pyridin-3-yl)thiazole-4-carbohydrazide

Molbank ◽  
10.3390/m1058 ◽  
2019 ◽  
Vol 2019 (2) ◽  
pp. M1058
Author(s):  
Vinuta Kamat ◽  
Rangappa Santosh ◽  
Suresh Nayak
Keyword(s):  
Escherichia Coli ◽  
Double Helix ◽  
Catalytic Amount ◽  
Target Compound ◽  
Addition Compound ◽  
E Coli ◽  
In Vitro Antibacterial Activity ◽  
Ft Ir ◽  
Dna Double Helix

5-methyl-2-(pyridin-3-yl)-1,3-thiazole-4-carbohydrazide (1) on treatment with 4-fluorobenzaldehyde in presence of catalytic amount of acetic acid, accessed the target compound (2) with the yield of 79%. The target compound was confirmed by 1H-NMR, 13C-NMR, FT-IR and LCMS. In vitro antibacterial activity against Staphylococcus aureus (S. Aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) were carried out and compound 2 showed promising activity against B. subtilis. In addition, compound 2 was analyzed for DNA binding study. It revealed that compound 2 has a promising affinity towards DNA double helix.

scholarly journals Interaction of Folk Medicinal Plants with Levofloxacin against Escherichia Coli

2020 ◽  
Vol 14 (3) ◽  
pp. 1855-1861
Author(s):  
Isra Tayseer ◽  
Hanan Azzam ◽  
Nehaya Al-Karablieh ◽  
Amal Mayyas ◽  
Talal Aburjai
Keyword(s):  
Escherichia Coli ◽  
Medicinal Plants ◽  
Plant Extracts ◽  
Curcuma Longa ◽  
Antimicrobial Activities ◽  
Thymus Vulgaris ◽  
Additive Interaction ◽  
Traditional Use ◽  
E Coli

The present study was conducted to assess the in vitro activities of folk medicinal plants in combination with levofloxacin against TG1 and mutant KAM3-1(∆acrB-∆tolC) Escherichia coli strains. Plants were chosen based on their traditional use in combination with antibiotics among laymen. Standard protocols were followed to examine the antimicrobial activity of plant extracts and levofloxacin against E. coli in term of their minimum inhibitory concentrations (MICs) and to evaluate the plant extracts-levofloxacin interaction using checkerboard method. Among the twelve plants investigated, Thymus vulgaris, Zingiber officinale, Teucrium polium, Matricaria chamomilla and Curcuma longa had the best antimicrobial activities against E. coli strains with MIC values at 250 μg/ml. It is noteworthy to mention that other folk plants extracts reveled no effects against E coli strains. Furthermore, additive interactions were observed between levofloxacin and T. polium or T. vulgaris against E. coli wild-type TG1 strain. There was no antagonism being observed in this study. The detection of additive interaction between the extracts and levofloxacin demonstrates the prospective of these folk medicinal plants as a source of compounds to modulate antibiotic resistance.

scholarly journals COMBINATION TEST OF CHINESE LEAF EXTRACT (Leucaena leucocephala folium) AND ALOE VERA INHIBITING GROWTH Escherichia coli

2020 ◽  
Vol 2 (2) ◽  
pp. 60-67
Author(s):  
Putra Rahmadea Utami ◽  
Chairani ◽  
Hendra Yudha
Keyword(s):  
Escherichia Coli ◽  
Leucaena Leucocephala ◽  
Aloe Vera ◽  
Ethanol Extract ◽  
Laboratory Research ◽  
The Public ◽  
E Coli ◽  
Experimental Laboratory ◽  
Medicinal Properties

Chinese petai (Leucaena leucocephala folium) and aloe vera (Aloe vera L.) have medicinal properties among the plants.  The objective of this study was to determine the number of inhibitory zones produced by the ethanol extract of Chinese petai and aloe vera on the growth of Escherichia coli. The research method was In-vitro Experimental Laboratory research design with the Kirby Bauer method. The samples used was Chinese petai and aloe vera with pure strains of E. coli. One Way ANOVA was used to compare the differences in inhibition of Chinese petai and aloe vera on the growth of E. coli. The results of a combination of Chinese petai and aloe vera extract test showed that there were significant differences in the concentration of 25 g, 50 g, 75 g, and 100 g (p <0.05). The ethanol extract of Chinese petai and aloe vera can inhibit the growth of E. coli. From the results of this study found that there was an interaction on the combination of ethanol extract of Chinese petai and aloe vera inhibiting the growth of E. coli with the most effective concentration being 100 g/mL. This study can find out the benefits of petai cina and aloe vera also the public will know the benefits and efficacy of Chinese petai and aloe vera leaves in medicine.

scholarly journals Evaluation preliminary phytochemistry and antimicrobial activity of extracts in Eugenia uniflora L. on Escherichia coli and Staphylococcus aureus

2021 ◽  
Vol 10 (13) ◽  
pp. e329101320579
Author(s):  
Alexandre Horácio Couto Bittencourt ◽  
Jaqueline Souza Machado ◽  
Mariana Garcia da Silva ◽  
Braz Antônio Pereira Cosenza
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Eugenia Uniflora ◽  
E Coli ◽  
And Staphylococcus Aureus

Devido ao aumento da resistência de patógenos humanos e animais aos medicamentos atuais, pesquisas por novos antimicrobianos têm sido incentivadas, principalmente por meio de plantas medicinais. Eugenia uniflora L., conhecida como pitangueira, é popularmente utilizada com diversas funções terapêuticas, justificando estudos nesta espécie. Assim, os objetivos deste estudo foram avaliar a atividade antibacteriana “in vitro” de extratos de folhas e cascas de Eugenia uniflora L. sobre Escherichia coli e Staphylococcus aureus. Para as etapas de triagem fitoquímica e microbiologia, foram utilizadas as metodologias usuais nessas áreas para obtenção dos extratos e avaliação da atividade antibacteriana com uso de controle positivo e negativo. Os resultados obtidos mostraram que no extrato das folhas foi verificada a presença de saponinas, flavonóides, alcalóides e taninos, enquanto na casca foram obtidos apenas saponinas e alcalóides. Os extratos da folha e da casca foram capazes de inibir o crescimento de Stapylococcus aureus apenas, promovendo halos de inibição de meio de 19,4 mm e 14,4 mm, respectivamente. As análises permitiram concluir que os extratos apresentam metabólitos secundários interessantes e de grande potencial antimicrobiano e que esses extratos foram capazes de inibir apenas as cepas de S. aureus, sendo resistentes às cepas de E. Coli.

scholarly journals Biological Properties of Structurally Related α-Helical Cationic Antimicrobial Peptides

1999 ◽  
Vol 67 (4) ◽  
pp. 2005-2009 ◽  
Author(s):  
Monisha G. Scott ◽  
Hong Yan ◽  
Robert E. W. Hancock
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Tumor Necrosis ◽  
Biological Properties ◽  
Cationic Antimicrobial Peptide ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Resistant Strains ◽  
Conventional Antibiotics ◽  
Necrosis Factor

ABSTRACT A series of α-helical cationic antimicrobial peptide variants with small amino acid changes was designed. Alterations in the charge, hydrophobicity, or length of the variant peptides did not improve the antimicrobial activity, and there was no statistically significant correlation between any of these factors and the MIC forPseudomonas aeruginosa, Escherichia coli, orSalmonella typhimurium. Individual peptides demonstrated synergy with conventional antibiotics against antibiotic-resistant strains of P. aeruginosa. The peptides varied considerably in the ability to bind E. coli O111:B4 lipopolysaccharide (LPS), and this correlated significantly with their antimicrobial activity and ability to block LPS-stimulated tumor necrosis factor and interleukin-6 production. In general, the peptides studied here demonstrated a broad range of activities, including antimicrobial, antiendotoxin, and enhancer activities.

scholarly journals Efficacy of trimethoprim in murine experimental infection with a thymidine kinase-deficient mutant of Escherichia coli.

1997 ◽  
Vol 41 (5) ◽  
pp. 1042-1045 ◽  
Author(s):  
T Tokunaga ◽  
K Oka ◽  
A Takemoto ◽  
Y Ohtsubo ◽  
N Gotoh ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Thymidine Kinase ◽  
Mutant Strain ◽  
Experimental Infection ◽  
Therapeutic Efficacy ◽  
Parent Strain ◽  
E Coli

The antimicrobial activity of trimethoprim is antagonized by thymidine in in vitro susceptibility tests. The purpose of this investigation was to determine whether this antagonism also occurred during experimental infection in mice, which have high serum thymidine concentrations. We derived a mutant strain of Escherichia coli, TT-48, incapable of utilizing exogenous thymidine from parent strain E. coli KC-14 and then investigated the in vitro and in vivo antimicrobial activities of trimethoprim, sulfamethoxazole, cefdinir, and ofloxacin against these strains. E. coli TT-48 lacked the activity of thymidine kinase, which catalyzes the conversion of thymidine to thymidylate, but its growth curve remained close to that of the parent strain. The MICs of all of the antimicrobial agents tested, except cefdinir, for the mutant strain were slightly inferior to those for the parent strain. The bactericidal effect of trimethoprim against the parent strain was antagonized by thymidine at concentrations of more than 1 microg/ml, while that against the mutant strain was not affected by thymidine even at the highest concentration (10 microg/ml). The therapeutic efficacy of trimethoprim in experimental murine infections was significantly higher when the mutant rather than the parent strain was used, whereas the therapeutic efficacy of cefdinir or ofloxacin, whose antimicrobial action is independent of folic acid synthesis, was the same with both strains. Unexpectedly, sulfamethoxazole also had similar efficacy against both strains. Thus, high thymidine concentrations antagonized the antimicrobial activity of trimethoprim in vitro and in vivo.

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