Evidence of an efflux pump in Serratia marcescens

Spontaneous mutants resistant to fluoroquinolones were obtained by exposing Serratia marcescens NIMA (wild-type strain) to increasing concentrations of ciprofloxacin both in liquid and on solid media. Frequencies of mutation ranged from 10-7 to 10-9. Active expulsion of antibiotic was explored as a possible mechanism of resistance in mutants as well as changes in topoisomerase target genes. The role of extrusion mechanisms in determining the emergence of multidrug-resistant bacteria was also examined. Mutants resistant to high concentrations of fluoroquinolones had a single mutation in their gyrA QRDR sequences, whereas the moderate resistance in the rest of mutants was due to extrusion of the drug

Evidence of an efflux pump in Serratia marcescens

Spontaneous mutants resistant to fluoroquinolones were obtained by exposing Serratia marcescens NIMA (wild-type strain) to increasing concentrations of ciprofloxacin both in liquid and on solid media. Frequencies of mutation ranged from 10-7 to 10-9. Active expulsion of antibiotic was explored as a possible mechanism of resistance in mutants as well as changes in topoisomerase target genes. The role of extrusion mechanisms in determining the emergence of multidrug-resistant bacteria was also examined. Mutants resistant to high concentrations of fluoroquinolones had a single mutation in their gyrA QRDR sequences, whereas the moderate resistance in the rest of mutants was due to extrusion of the drug

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

Ocorrência e degradação de quinolonas por processos oxidativos avançados

In this review, the presence of quinolones in the environment, their risks and the available processes for water decontamination were addressed. Their occurrence in surface waters and also in soil raises concerns about the risk of the development of resistant bacteria and other potential chronic effects. AOPs (UV/H2O2, Fenton, photo-Fenton, and UV/TiO2) and ozonation proved effective for degrading these emerging contaminants due to hydroxyl radical formation, surpassing the efficacy of conventional methods. In addition, the main degradation mechanisms of these drugs as well as data on residual biological activity were analyzed.

Identification and antimicrobial resistance of members from the Enterobacteriaceae family isolated from canaries (Serinus canaria)

Abstract: The Enterobacteriaceae family contains potentially zoonotic bacteria, and their presence in canaries is often reported, though the current status of these in bird flocks is unknown. Therefore, this study aimed to identify the most common genera of enterobacteria from canaries (Serinus canaria) and their antimicrobial resistance profiles. From February to June of 2013, a total of 387 cloacal swab samples from eight domiciliary breeding locations of Fortaleza city, Brazil, were collected and 58 necropsies were performed in canaries, which belonged to the Laboratory of Ornithological Studies. The samples were submitted to microbiological procedure using buffered peptone water and MacConkey agar. Colonies were selected according to their morphological characteristics on selective agar and submitted for biochemical identification and antimicrobial susceptibility. A total of 61 isolates were obtained, of which 42 were from cloacal swabs and 19 from necropsies. The most isolated bacteria was Escherichia coli with twenty five strains, followed by fourteen Klebsiellaspp., twelve Enterobacterspp., seven Pantoea agglomerans, two Serratiaspp. and one Proteus mirabilis. The antimicrobial to which the strains presented most resistance was sulfonamides with 55.7%, followed by ampicillin with 54.1% and tetracycline with 39.3%. The total of multidrug-resistant bacteria (MDR) was 34 (55.7%). In conclusion, canaries harbor members of the Enterobacteriaceae family and common strains present a high antimicrobial resistance rate, with a high frequency of MDR bacteria.

Monocouches peptidiques auto-assemblées et applications dans le domaine des biocapteurs de résonance de plasmon de surfaces

Ces travaux visent à étendre les applications de la résonance de plasmons de surface (SPR) L’objectif est d’offrir des outils diagnostics plus rapides, efficaces et simple d’utilisation pour diagnostiquer ou effectuer le suivi de conditions cliniques. Pour se faire, un nouveau type d’instrumentation SPR basé sur l’utilisation d’un prisme d’inversion (dove) a permis d’atteindre une limite de détection (LOD) de 10-6 unité d’indice de réfraction (RIU), une valeur comparable aux instruments commerciaux complexes tout en demeurant peu dispendieux, robuste et simple d’utilisation. Les travaux présentés dans cet ouvrage visent, dans un second temps, à réduire les interactions nonspécifiques (NSB) entre la surface des biocapteurs SPR et les composants de la matrice biologique complexe telles que: l’urine, le lysat cellulaire, le sérum et le sang. Ces dernières induisent des réponses empêchant l’utilisation de biocapteurs SPR en milieux complexes. Les acides aminés (AA) offrent une grande variété de propriétés physico-chimiques permettant la mise au point de monocouches auto-assemblées (SAM) aux propriétés diverses. Initialement, 19 des 20 acides aminés naturels ont été attachés à l’acide 3-mercaptopropionique (3-MPA) formant des SAMs peptidomimétiques. La quantité d’interactions nonspécifiques engendrées par ces différentes surfaces a été mesurée en exposant ces surfaces au sérum sanguin bovin complet variant de 400 ng/cm² jusqu’à 800 ng/cm². La détection à l’aide de ces surfaces de la β-lactamase (une enzyme responsable de la résistance aux antibiotiques au niveau μM) a démontré la possibilité d’employer ces surfaces pour bâtir des biocapteurs SPR. Des peptides de longueur allant de 2 à 5 résidus attachés à 3-MPA ont été synthétisés sur support solide. Cette étude a démontré que l’augmentation de la longueur des peptides formés d’AA résistants aux NBS accroit leur résistance jusqu’à 5 résidus. Le composé le plus performant de ce type (3-MPA-(Ser)5-OH) a permis d’atteindre 180 ng/cm². Cette valeur est similaire à celle des meilleures surfaces disponibles commercialement, notamment les surfaces de polyethylène glycol (PEG) à 100 ng/cm². Des surfaces de 3-MPA-(Ser)5-OH ont permis l’étalonnage de la β-lactamase et sa quantification directe dans un lysat cellulaire. La LOD pour ces biocapteurs est de 10 nM. Une troisième génération de surfaces peptidiques binaires a permis la réduction de la NSB jusqu’à un niveau de 23±10 ng/cm² une valeur comparable aux meilleures surfaces disponibles. Ces surfaces ont permis l’étalonnage d’un indicateur potentiel du cancer la metalloprotéinase-3 de matrice (MMP-3). Les surfaces formées de peptides binaires (3-MPA-H3D2-OH) ont permis la quantification directe de la MMP-3 dans le sérum sanguin complet. Une quatrième génération de surfaces peptidiques a permis de réduire davantage le niveau de NSB jusqu’à une valeur de 12 ± 11 ng/cm². Ces surfaces ont été modifiées en y attachant une terminaison de type acide nitriloacétique (NTA) afin d’y attacher des biomolécules marquées par six résidus histidines terminaux. Ces surfaces ont permis le développement d’une méthode rapide de balayage des ligands ciblant le « cluster of differenciation-36 » (CD36). L’étude d’électroformation des monocouches de peptide a permis de déterminer les conditions de formation optimales d’une couche de 3-MPA-HHHDD-OH permettant ainsi la formation de monocouches résistantes au NSB en moins de 6 minutes en appliquant un potentiel de formation de 200mV vs Ag/AgCl.

Biochemical and molecular studies of cadmium resistance and metal biosorption in bacterial species isolated from cochin environment

Cochin, commercial capital of Kerala, located on the west-coast of South India has a large number of chemical and sea food industries. Earlier studies in the past indicated that these industries contribute to heavy metal pollution, particularly mercury, copper, and cadmium, in Cochin backwater. Hence, in the present study, it was desired to isolate cadmium resistant bacteria from effluent discharged by chemical industry with a view to develop an ideal bioremediation process for safe discharge of industrial effluent in to the nearby aquatic environment. Effluent from three industries, located in the industrial belt of Cochin, were collected from the discharge point and cadmium resistant bacteria were screened using standard microbiological techniques

Vibrio harveyi phages: Isolation, characterization and evaluation of their potential as phage therapeutics on Vibrio harveyi in shrimp hatcheries

Aquaculture is a global industry providing food and employment thereby contributing to the economy. For the sustenance of aquaculture, disease management is a major requirement. Among the bacterial pathogens Vibrio harveyi remains to be the major one especially in shrimp culture systems. Rapid and mass mortality of shrimp larvae due to Vibrio harveyi infection is well known, and the pathogen causes serious economic losses in grow out systems as well. It suggests that a well defined management strategy has to be built up to protect the crop from Vibrio harveyi infection in aquaculture systems. Antibiotics have been the choice for quite some times which led to residues in meat and development of multidrug resistant bacteria which invited ban on their application. In this context several alternate options have been thought off such as probiotics, immunostimulants and vaccines. Phage therapy is yet another option. Phages being natural parasites of bacteria and are abundant in aquatic environments their application to control bacterial pathogens in aquaculture has commendable potential in lieu of antibiotics. For that matter the therapeutic effect of phages has been proven in several antibiotic resistant pathogens inclusive of Vibrio harveyi.

Revision sistemática: Factores asociados a colonización e infección por bacterias gram negativas resistentes a carbapenemicos

INTRODUCCIÓN: Los carbapenémicos (CP) son una de las últimas líneas de tratamiento para infecciones por microorganismos multirresistentes (MDR), especialmente Gram-negativos productores de betalactamasas de espectro extendido. Es creciente la preocupación a nivel mundial por el aumento de aislamientos resistentes a CP, en EEUU hasta 60% de las infecciones nosocomiales son causadas por bacterias MDR. En la Unión Europea, cerca de 25.000 pacientes mueren anualmente por esta causa. En Latinoamérica hay una tendencia creciente en las tasas de resistencia.OBJETIVO: Identificar y describir factores protectores o de riesgo, relacionados con colonización o infección por Gram negativos resistentes a CP en pacientes adultos hospitalizados, mediante una revisión sistemática de la literatura.MÉTODOS: Revisión sistemática de literatura, búsqueda de estudios observacionales analíticos en las bases de datos PubMed, Embase, Scopus, BVS, Scielo y búsqueda de literatura gris, publicados desde el 01/01/2004 al 15/04/2015. Se evalúo la calidad de los estudios con escala Newcastle-Ottawa y FLC Osteba. RESULTADOS: Se seleccionaron 36 estudios de alta calidad, diseño de casos y controles. Los factores de riesgo estadísticamente significativos observados son estancia en UCI OR:36.46, insuficiencia renal aguda OR:6.23, diálisis OR:10.80 ventilación mecánica OR:17.5, cateterismo vesical OR:14.3, uso de carbapenémicos OR:18,52,quinolonas OR17.30, cefepime OR:28.05, glicopéptidos OR:19.1; metronidazol OR:4.17, p:0.03, colistina OR:12.1, linezolid OR:7 CONCLUSIÓN: Pese a que hay alta heterogeneidad en las variables incluidas en los estudios, se encontró que los factores de riesgo principales para adquirir GNR-CP en pacientes hospitalizados son: antecedente de insuficiencia renal aguda y diálisis, ventilación mecánica, cateterismo vesical, estancia en UCI y uso previo de antibióticos carbapenémicos, quinolonas, cefepime, glicopéptidos, metronidazol, linezolid y colistina. No se hallaron factores protectores. factores de riesgo

Farm-level risk factors for fluoroquinolone resistance in E-coli and thermophilic Campylobacter spp. on finisher pig farms

Logistic regression, supported by other statistical analyses was used to explore the possible association of risk factors with the fluoroquinolone (FQ)-resistance status of 108 pig finisher farms in Great Britain. The farms were classified as 'affected' or 'not affected' by FQ-resistant E. coli or Campylobacter spp. on the basis of isolation of organisms from faecal samples on media containing 1 mg/l FQ. The use of FQ was the most important factor associated with finding resistant E. coli and/or Campylobacter, which were found on 79% (FQ-resistant E. coli) and 86% (FQ-resistant Campylobacter) of farms with a history of FQ use. However, resistant bacteria were also found on 19% (FQ-resistant E. coli) and 54% (FQ-resistant Campylobacter) of farms with no history of FQ use. For FQ-resistant E. coli, biosecurity measures may be protective and there was strong seasonal variation, with more farms found affected when sampled in the summer. For FQ-resistant Campylobacter, the buying-in of grower stock may increase risk and good on-farm hygiene may be protective. The findings suggest that resistant organisms, particularly Campylobacter, may spread between pig farms.

A survey of fluoroquinolone resistance in Escherichia coli and thermophilic Campylobacter spp. on poultry and pig farms in Great Britain

Aims: To estimate the proportions of farms on which broilers, turkeys and pigs were shedding fluoroquinolone (FQ)-resistant Escherichia coli or Campylobacter spp. near to slaughter. Methods and Results: Freshly voided faeces were collected on 89 poultry and 108 pig farms and cultured with media containing 1.0 mg l(-1) ciprofloxacin. Studies demonstrated the specificity of this sensitive method, and both poultry and pig sampling yielded FQ-resistant E. coli on 60% of farms. FQ-resistant Campylobacter spp. were found on around 22% of poultry and 75% of pig farms. The majority of resistant isolates of Campylobacter (89%) and E. coli (96%) tested had minimum inhibitory concentrations for ciprofloxacin of >= 8 mg l(-1). The proportion of resistant E. coli and Campylobacter organisms within samples varied widely. Conclusions: FQ resistance is commonly present among two enteric bacterial genera prevalent on pig and poultry farms, although the low proportion of resistant organisms in many cases requires a sensitive detection technique. Significance and Impact of the Study: FQ-resistant bacteria with zoonotic potential appear to be present on a high proportion of UK pig and poultry farms. The risk this poses to consumers relative to other causes of FQ-resistant human infections remains to be clarified.