bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation of a
Lactobacillus salivarius
Strain and Purification of Its Bacteriocin, Which Is Inhibitory to
Campylobacter jejuni
in the Chicken Gastrointestinal System
Authors: Stern N. J. , Svetoch E. A. , Eruslanov B. V. , Perelygin V. V. , Mitsevich E. V. , Mitsevich I. P. , Pokhilenko V. D. , Levchuk V. P. , Svetoch O. E. , Seal B. S. 
Published: August 2006

ABSTRACT

We evaluated anti-
Campylobacter jejuni
activity among >1,200 isolates of different lactic acid bacteria.
Lactobacillus salivarius
strain NRRL B-30514 was selected for further study. The cell-free, ammonium sulfate precipitate from the broth culture was termed the crude antimicrobial preparation. Ten microliters of the crude preparation created a zone of
C. jejuni
growth inhibition, and growth within the zone resumed when the crude preparation was preincubated with proteolytic enzymes. Bacteriocin OR-7, derived from this crude preparation, was further purified using ion-exchange and hydrophobic-interaction chromatography. The determined amino acid sequence was consistent with class IIa bacteriocins. Interestingly, OR-7 had sequence similarity, even in the C-terminal region, to acidocin A, which was previously identified from
L. acidophilus
and had activity only to gram-positive bacteria, whereas OR-7 had activity to a gram-negative bacterium. Bacteriocin activity was stable following exposure to 90°C for 15 min, also consistent with these types of antibacterial peptides. The purified protein was encapsulated in polyvinylpyrrolidone and added to chicken feed. Ten day-of-hatch chicks were placed in each of nine isolation units; two groups of birds were challenged with each of four
C. jejuni
isolates (one isolate per unit). At 7 days of age, one group of birds was treated with bacteriocin-emended feed for 3 days, and one group was left untreated. At 10 days of age, the birds were sacrificed and the challenge strain was enumerated from the bird cecal content. Bacteriocin treatment consistently reduced colonization at least one millionfold compared with levels found in the untreated groups. Nonchallenged birds were never colonized by
C. jejuni
. Bacteriocin from
L. salivarius
NRRL B-30514 appears potentially very useful to reduce
C. jejuni
in poultry prior to processing.
Increase of the M Phenotype among Erythromycin-Resistant
Streptococcus pneumoniae
Isolates from Spain Related to the Serotype 14 Variant of the Spain
9V
-3 Clone
Authors: Ardanuy C. , Fenoll A. , Berrón S. , Calatayud L. , Liñares J. ,   the Spanish Pneumococcal Infection Study Network
Published: August 2006

ABSTRACT

Between 1998 and 2003 the rate of erythromycin resistance among pneumococci in Spain was 34.4%. Although the MLS
B
phenotype was prevalent (94.7%), the rate of the M phenotype increased from 3.3% to 8.9% (
P
< 0.01). Clonal dissemination of
mef
(E)-carrying strains of serotype 14 variant of the Spain
9V
-3 clone was the major contributor to this increase.
In Vivo Reversion to the Wild-Type β-Lactam Resistance Phenotype Mediated by a Plasmid CarryingampRandqnrA1inEnterobacter cloacae
Authors: González-López J. J. , Sabaté M. , Lavilla S. , Larrosa M. N. , Bartolomé R. M. , Prats G. 
Published: August 2006

ABSTRACTResistance to β-lactams and quinolones in two isogenicEnterobacter cloacaeisolates was studied. One was susceptible to cefoxitin and amoxicillin-clavulanate. The other one showed its natural β-lactam resistance pattern. Both isolates had a nonfunctional AmpR regulator. However, within the second one, the presence of a plasmid carryingampRandqnrA1allowed reversion to the wild-type β-lactam resistance phenotype and decreased susceptibility to fluoroquinolones.
Mobilizable IncQ-Related Plasmid Carrying a New Quinolone Resistance Gene,
qnrS2
, Isolated from the Bacterial Community of a Wastewater Treatment Plant
Authors: Bönemann Gabriele , Stiens Michael , Pühler Alfred , Schlüter Andreas 
Published: August 2006

ABSTRACT

Plasmid-encoded quinolone resistance was previously reported for different bacteria isolated from patients not only in the United States and Asia but also in Europe. Here we describe the isolation, by applying a new selection strategy, of the quinolone resistance plasmid pGNB2 from an activated sludge bacterial community of a wastewater treatment plant in Germany. The hypersensitive
Escherichia coli
strain KAM3 carrying a mutation in the multidrug efflux system genes
acrAB
was transformed with total plasmid DNA preparations isolated from activated sludge bacteria and subsequently selected on medium containing the fluoroquinolone norfloxacin. This approach resulted in the isolation of plasmid pGNB2 conferring decreased susceptibility to nalidixic acid and to different fluoroquinolones. Analysis of the pGNB2 nucleotide sequence revealed that it is 8,469 bp in size and has a G+C content of 58.2%. The plasmid backbone is composed of a replication initiation module (
repA-repC
) belonging to the IncQ-family and a two-component mobilization module that confers horizontal mobility to the plasmid. In addition, plasmid pGNB2 carries an accessory module consisting of a transposon Tn
1721
remnant and the quinolone resistance gene,
qnrS2
, that is 92% identical to the
qnrS
gene located on plasmid pAH0376 from
Shigella flexneri
2b. QnrS2 belongs to the pentapeptide repeat protein family and is predicted to protect DNA-gyrase activity against quinolones. This is not only the first report on a completely sequenced plasmid mediating quinolone resistance isolated from an environmental sample but also on the first
qnrS
-like gene detected in Europe.
A Novel Extended-Spectrum TEM-Type β-Lactamase, TEM-138, from
Salmonella enterica
Serovar Infantis
Authors: Chouchani Chedly , Berlemont Renaud , Masmoudi Afef , Galleni Moreno , Frere Jean-Marie , Belhadj Omrane , Ben-Mahrez Kamel 
Published: August 2006

ABSTRACT

A novel natural TEM β-lactamase with extended-spectrum activity, TEM-138, was identified in a ceftazidime-resistant clinical isolate of
Salmonella enterica
serovar Infantis. Compared to TEM-1, TEM-138 contains the following mutations: E104K, N175I, and G238S. The
bla
TEM-138
gene was located on a 50-kb transferable plasmid. Expression studies with
Escherichia coli
revealed efficient ceftazidimase and cefotaximase activities for TEM-138.
Tetracyclines Specifically Target the Apicoplast of the Malaria Parasite
Plasmodium falciparum
Authors: Dahl Erica L. , Shock Jennifer L. , Shenai Bhaskar R. , Gut Jiri , DeRisi Joseph L. , Rosenthal Philip J. 
Published: August 2006

ABSTRACT

Tetracyclines are effective but slow-acting antimalarial drugs whose mechanism of action remains uncertain. To characterize the antimalarial mechanism of tetracyclines, we evaluated their stage-specific activities, impacts on parasite transcription, and effects on two predicted organelle targets, the apicoplast and the mitochondrion, in cultured
Plasmodium falciparum
. Antimalarial effects were much greater after two 48-h life cycles than after one cycle, even if the drugs were removed at the end of the first cycle. Doxycycline-treated parasites appeared morphologically normal until late in the second cycle of treatment but failed to develop into merozoites. Doxycycline specifically impaired the expression of apicoplast genes. Apicoplast morphology initially appeared normal in the presence of doxycycline. However, apicoplasts were abnormal in the progeny of doxycycline-treated parasites, as evidenced by a block in apicoplast genome replication, a lack of processing of an apicoplast-targeted protein, and failure to elongate and segregate during schizogeny. Replication of the nuclear and mitochondrial genomes and mitochondrial morphology appeared normal. Our results demonstrate that tetracyclines specifically block expression of the apicoplast genome, resulting in the distribution of nonfunctional apicoplasts into daughter merozoites. The loss of apicoplast function in the progeny of treated parasites leads to a slow but potent antimalarial effect.
Combination of Suboptimal Doses of Inhibitors Targeting Different Domains of LtrMDR1 Efficiently Overcomes Resistance of
Leishmania
spp. to Miltefosine by Inhibiting Drug Efflux
Authors: Pérez-Victoria José M. , Cortés-Selva Fernando , Parodi-Talice Adriana , Bavchvarov Boris I. , Pérez-Victoria F. Javier , Muñoz-Martínez Francisco , Maitrejean Mathias , Costi M. Paola , Barron Denis , Di Pietro Attilio , Castanys Santiago , Gamarro Francisco 
Published: August 2006

ABSTRACT

Miltefosine (hexadecylphosphocholine) is the first orally active drug approved for the treatment of leishmaniasis. We have previously shown the involvement of LtrMDR1, a P-glycoprotein-like transporter belonging to the ATP-binding cassette superfamily, in miltefosine resistance in
Leishmania
. Here we show that overexpression of LtrMDR1 increases miltefosine efflux, leading to a decrease in drug accumulation in the parasites. Although LtrMDR1 modulation might be an efficient way to overcome this resistance, a main drawback associated with the use of P-glycoprotein inhibitors is related to their intrinsic toxicity. In order to diminish possible side effects, we have combined suboptimal doses of modulators targeting both the cytosolic and transmembrane domains of LtrMDR1. Preliminary structure-activity relationships have allowed us to design a new and potent flavonoid derivative with high affinity for the cytosolic nucleotide-binding domains. As modulators directed to the transmembrane domains, we have selected one of the most potent dihydro-β-agarofuran sesquiterpenes described, and we have also studied the effects of two of the most promising, latest-developed modulators of human P-glycoprotein, zosuquidar (LY335979) and elacridar (GF120918). The results show that this combinatorial strategy efficiently overcomes P-glycoprotein-mediated parasite miltefosine resistance by increasing intracellular miltefosine accumulation without any side effect in the parental, sensitive,
Leishmania
line and in different mammalian cell lines.
Intracellular Penetration and Activity of DX-619 in Human Polymorphonuclear Leukocytes
Authors: García Isabel , Ballesta Sofía , Murillo Concepción , Perea Evelio J. , Pascual Álvaro 
Published: August 2006

ABSTRACTThe intracellular penetration and activity of DX-619 in human polymorphonuclear leukocytes have been evaluated. DX-619 reached intracellular concentrations 10 times higher than the extracellular concentrations reached. Uptake was rapid, reversible, nonsaturable, and affected by environmental temperature, some metabolic inhibitors, and a soluble membrane activator. DX-619 showed intracellular activity againstStaphylococcus aureus.
Effect of Treatment Duration on Pharmacokinetic/Pharmacodynamic Indices Correlating with Therapeutic Efficacy of Ceftazidime in Experimental
Klebsiella pneumoniae
Lung Infection
Authors: Bakker-Woudenberg Irma A. J. M. , ten Kate Marian T. , Goessens Wil H. F. , Mouton Johan W. 
Published: August 2006

ABSTRACT

The pharmacokinetic/pharmacodynamic (PK/PD) indices that define the therapeutic effect of the beta-lactam ceftazidime in a rat model of
Klebsiella pneumoniae
lung infection were investigated in relation to treatment duration and treatment endpoint. Treatment was started 24 h after infection with dosing regimens of 3.1 up to 1,600 mg/kg of body weight/day and dosing every 6, 12, or 24 h. When animals were treated for a relatively short period of 48 h, the duration of time that unbound plasma ceftazidime levels exceeded the MIC of the antibiotic for the infecting strain was the index that best correlated with therapeutic efficacy in terms of significant bacterial killing in the infected lung (microbiological effect). The maximum effect was reached when plasma ceftazidime levels were above the MIC for 60 to 70% of the dosing interval. However, when the treatment duration was extended to a relatively long period of 18 days instead of 48 h and animal survival rate instead of microbiological efficacy was taken as the endpoint, the
f
AUC/MIC ratio (where AUC is the area under the concentration-time curve) was the PK/PD index that best correlated with therapeutic efficacy. The PK/PD indices that effect 50% survival of rats for the
f
AUC/MIC ratios were 18.0 (95% confidence interval [95% CI], 16.3 to 19.9), 20.2 (95% CI, 13.8 to 29.4), and 27.9 (95% CI, 21.3 to 36.5) for the schedules of administration of every 6, 12, and 24 h, respectively. The
f
AUC/MIC needed for 100% survival was >100. We conclude that the PK/PD index that best correlates with outcome is dependent on the duration of treatment and/or the parameter of outcome. The effect of long-term treatment should be studied more extensively in other models of infection.
Efficacy of Cethromycin, a New Ketolide, against
Streptococcus pneumoniae
Susceptible or Resistant to Erythromycin in a Murine Pneumonia Model
Authors: Azoulay-Dupuis E. , Mohler J. , Bédos J. P. , Barau C. , Fantin B. 
Published: August 2006

ABSTRACT

Cethromycin is a ketolide with in vitro activity against macrolide-sensitive and -resistant strains of
Streptococcus pneumoniae
. We compared its in vivo efficacy to erythromycin in a mouse model of acute pneumonia induced by two virulent clinical strains: a serotype 3 susceptible strain (P-4241) (MICs: erythromycin, 0.03 μg/ml; cethromycin, 0.015 μg/ml) and a serotype 1 strain resistant to erythromycin (P-6254; phenotypically MLSB constitutive) (MICs: erythromycin, 1,024 μg/ml; cethromycin, 0.03 μg/ml). Immunocompetent mice were infected with 10
5
CFU of each strain. Six treatments given either subcutaneously (s.c.) or per os (p.o.) at 12-h intervals were initiated at 6 or 12 h after infection. Against P-4241, cethromycin given s.c. at 25 or 12.5 mg/kg protected 100% of the animals, with lungs and blood completely cleared of bacteria. Given p.o., cethromycin maintained its efficacy with 100 and 86% survival at 25 and 12.5 mg/kg, respectively. Erythromycin, given s.c. at 50 or 37.5 mg/kg, provided 50 and 38% survival rates, respectively. Against P-6254, cethromycin was effective at 25 mg/kg (100% survival) regardless of the administration route, whereas only 25 and 8% of animals survived after a 75-mg/kg erythromycin treatment given s.c. and p.o., respectively. The serum protein binding levels of cethromycin were 94.8 and 88.5% after doses of 12.5 and 25 mg/kg, respectively. The higher in vivo activity of cethromycin compared to erythromycin could be explained by favorable pharmacokinetic/pharmacodynamic indexes against P-6254 but not against P-4241.
Activity of Picolinic Acid in Combination with the Antiprotozoal Drug Quinacrine against
Mycobacterium avium
Complex
Authors: Shimizu Toshiaki , Tomioka Haruaki 
Published: August 2006

ABSTRACT

We studied the in vitro and in vivo antimicrobial activities of picolinic acid (PA) in combination with the antiprotozoal drug quinacrine against intramacrophage
Mycobacterium avium
complex (MAC). Quinacrine significantly potentiated the anti-MAC activity of PA, suggesting the usefulness of this combination in the clinical control of MAC infection.
Detection of Extended-Spectrum β-Lactamases in Clinical Isolates of
Pseudomonas aeruginosa
Authors: Jiang Xiaofei , Zhang Zhe , Li Min , Zhou Danqiu , Ruan Feiyi , Lu Yuan 
Published: August 2006

ABSTRACT

With the occurrence of extended-spectrum β-lactamases (ESBLs) in
Pseudomonas aeruginosa
being increasingly reported worldwide, there is a need for a reliable test to detect ESBLs in clinical isolates of
P. aeruginosa
. In our study, a total of 75 clinical isolates of
P. aeruginosa
were studied. Nitrocefin tests were performed to detect the β-lactamase enzyme; isoelectric focusing electrophoresis, PCR, and PCR product sequencing were designed to further characterize the contained ESBLs. Various ESBL-screening methods were designed to compare the reliabilities of detecting ESBLs in clinical isolates of
P. aeruginosa
whose β-lactamases were well characterized. Thirty-four of 36 multidrug-resistant
P. aeruginosa
clinical isolates were positive for ESBLs.
bla
VEB-3
was the most prevalent ESBL gene in
P. aeruginosa
in our study. Among the total of 34 isolates that were considered ESBL producers, 20 strains were positive using conventional combined disk tests and 10 strains were positive using a conventional double-disk synergy test (DDST) with amoxicillin-clavulanate, expanded-spectrum cephalosporins, aztreonam, and cefepime. Modifications of the combined disk test and DDST, which consisted of shorter distances between disks (20 mm instead of 30 mm) and the use of three different plates that contained cloxacillin (200 μg/ml) alone, Phe-Arg β-naphthylamide dihydrochloride (MC-207,110; 20 μg/ml) alone, and both cloxacillin (200 μg/ml) and MC-207,110 (20 μg/ml) increased the sensitivity of the tests to 78.8%, 91.18%, 85.29%, and 97.06%.
Comparative Efficacies of Amoxicillin, Clindamycin, and Moxifloxacin in Prevention of Bacteremia following Dental Extractions
Authors: Diz Dios P. , Tomás Carmona I. , Limeres Posse J. , Medina Henríquez J. , Fernández Feijoo J. , Álvarez Fernández M. 
Published: August 2006

ABSTRACT

We evaluated the efficacies of oral prophylactic treatment with amoxicillin (AMX), clindamycin (CLI), and moxifloxacin (MXF) in the prevention of bacteremia following dental extractions (BDE). Two hundred twenty-one adults who required dental extractions under general anesthesia were randomly assigned to a control group, an AMX group, a CLI group, and an MXF group (the individuals in the drug treatment groups received 2 g, 600 mg, and 400 mg, respectively, 1 to 2 h before anesthesia induction). Venous blood samples were collected from each patient at the baseline and 30 s, 15 min, and 1 h after the dental extractions. The samples were inoculated into BACTEC Plus aerobic and anaerobic blood culture bottles and were processed in a BACTEC 9240 instrument. Subculture and the further identification of the isolated bacteria were performed by conventional microbiological techniques. The prevalences of BDE in the control group, AMX group, CLI group, and MXF group were 96, 46, 85, and 57%, respectively, at 30 s; 64, 11, 70, and 24%, respectively, at 15 min; and 20, 4, 22, and 7%, respectively, at 1 h.
Streptococcus
spp. were the most frequently identified bacteria in all groups (44 to 68%), with the lowest percentage being detected in the AMX group (44%). AMX and MXF prophylaxis showed high efficacies in reducing the prevalence and duration of BDE, but CLI prophylaxis was noneffective. As a consequence, MXF prophylaxis is a promising antibiotic alternative for the prevention of BDE when beta-lactams are not indicated.
Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Binding Domain of
Porphyromonas gingivalis
Gingipain
Authors: Xie Hua , Belogortseva Natalya I. , Wu Jie , Lai Wei-Hong , Chen Chin-ho 
Published: August 2006

ABSTRACT

Human immunodeficiency virus (HIV) transmission through saliva is extremely low. Several oral components, including secretory immunoglobulin A and secretory leukocyte protease inhibitor, are known as potential inhibitory agents of HIV oral transmission. Here we examined anti-HIV activity of oral bacterial components. We showed that recombinant protein HGP44 derived from
Porphyromonas gingivalis
, one of the primary infectious agents of periodontitis, was capable of inhibiting HIV type 1 (HIV-1) replication. HGP44 bound specifically to HIV-1 gp120 and blocked HIV-1 envelope-mediated membrane fusion. These findings suggest that HGP44 of
P. gingivalis
can inhibit HIV-1 infection by blocking HIV-1 entry.
High-Affinity Aptamers to Subtype 3a Hepatitis C Virus Polymerase Display Genotypic Specificity
Authors: Jones Louisa A. , Clancy Leighton E. , Rawlinson William D. , White Peter A. 
Published: August 2006

ABSTRACTResearch into antiviral agents directed at hepatitis C virus (HCV) proteins is commonly based and tested on a single genotype, namely, genotype 1. This is despite the high level of variability of the RNA virus and the frequency of infection with genotypes other than genotype 1. The systematic evolution of ligands by exponential enrichment (SELEX) is a novel in vitro approach used in this study that allows rapid screening of vast nucleic acid libraries to isolate sequences (termed aptamers) that bind to target proteins with high affinity. The SELEX approach was used in the present study to isolate DNA aptamers to the RNA-dependent RNA polymerase (RdRp) (nonstructural protein 5B [NS5B]) of HCV subtype 3a, with the aim of inhibiting polymerase activity. Ten rounds of selection were performed using a Biacore 2000 as the partitioning system. Two aptamers, r10/43 and r10/47, were chosen for further studies on the basis of their abilities to bind the HCV RdRp and inhibit polymerase activity. The affinities (equilibrium dissociation constants) of these aptamers for the HCV subtype 3a polymerase were estimated to be 1.3 ± 0.3 nM (r10/43) and 23.5 ± 6.7 nM (r10/47). The inhibition constants of r10/43 and r10/47 were estimated to be 1.4 ± 2.4 nM and 6.0 ± 2.3 nM, respectively. Inhibition of HCV 3a polymerase was specific for r10/47, while r10/43 also demonstrated some inhibitory effect on norovirus and φ6 polymerase activity. Neither r10/43 nor r10/47 was able to inhibit the RdRp activity of HCV genotype 1a and 1b polymerases. This study is the first description of an inhibitor specific to the HCV subtype 3a polymerase.
Critical Design Features of Phenyl Carboxylate-Containing Polymer Microbicides
Authors: Rando Robert F. , Obara Sakae , Osterling Mark C. , Mankowski Marie , Miller Shendra R. , Ferguson Mary L. , Krebs Fred C. , Wigdahl Brian , Labib Mohamed , Kokubo Hiroyasu 
Published: August 2006

ABSTRACT

Recent studies of cellulose-based polymers substituted with carboxylic acids like cellulose acetate phthalate (CAP) have demonstrated the utility of using carboxylic acid groups instead of the more common sulfate or sulfonate moieties. However, the pK
a
of the free carboxylic acid group is very important and needs careful selection. In a polymer like CAP the pK
a
is approximately 5.28. This means that under the low pH conditions found in the vaginal lumen, CAP would be only minimally soluble and the carboxylic acid would not be fully dissociated. These issues can be overcome by substitution of the cellulose backbone with a moiety whose free carboxylic acid group(s) has a lower pK
a
. Hydroxypropyl methylcellulose trimellitate (HPMCT) is structurally similar to CAP; however, its free carboxylic acids have pK
a
s of 3.84 and 5.2. HPMCT, therefore, remains soluble and molecularly dispersed at a much lower pH than CAP. In this study, we measured the difference in solubility and dissociation between CAP and HPMCT and the effect these parameters might have on antiviral efficacy. Further experiments revealed that the degree of acid substitution of the cellulose backbone can significantly impact the overall efficacy of the polymer, thereby demonstrating the need to optimize any prospective polymer microbicide with respect to pH considerations and the degree of acid substitution. In addition, we have found HPMCT to be a potent inhibitor of CXCR4, CCR5, and dual tropic strains of human immunodeficiency virus in peripheral blood mononuclear cells. Therefore, the data presented herein strongly support further evaluation of an optimized HPMCT variant as a candidate microbicide.