scholarly journals Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization

2021 ◽  
Vol 12 ◽  
Author(s):  
Nuria Carpena ◽  
Kerry Richards ◽  
Teresita D. J. Bello Gonzalez ◽  
Alberto Bravo-Blas ◽  
Nicholas G. Housden ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Delivery ◽  
Controlled Release ◽  
Animal Models ◽  
Targeted Delivery ◽  
Intestinal Colonization ◽  
Ph Responsive ◽  
Human Gut ◽  
E Coli

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.

Chemostat modeling ofEscherichia colipersistence in conventionalized mono-associated and streptomycin-treated mice

2001 ◽  
Vol 47 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Camilla Rang ◽  
Tore Midtvedt ◽  
Søren Molin ◽  
Lin Chao
Keyword(s):  
Escherichia Coli ◽  
Doubling Time ◽  
Keystone Species ◽  
Intestinal Bacteria ◽  
Intestinal Colonization ◽  
Chemostat Model ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Intestinal Ecology

We have previously shown that Escherichia coli BJ4 has similar doubling time in mice that are mono-associated (having only the inoculated E. coli BJ4) or streptomycin-treated (having mainly gram-positive bacteria plus the inoculated E. coli BJ4). We also showed that when the mice were conventionalized (fed cecum homogenate from conventional mice or ones with a complete microbial flora), the introduction of complete flora in both cases increased the in vivo doubling time, while decreasing the colony counts in fecal samples. To determine whether the increase in doubling time could explain the decrease in colony counts, we analyzed our previous results by a chemostat model. The analysis shows that the increasing doubling time alone is sufficient to explain the decrease in colony counts in mono-associated mice, but not in the streptomycin-treated mice. The observed decreasing rate in colony counts in streptomycin-treated mice is slower than predicted. Furthermore, whereas the model predicted a decrease to extinction in both mice, the E. coli persist at a frequency 10-80 times higher in streptomycin-treated mice than in mono-associated mice. Thus, while a chemostat model is able to explain some of the population dynamics of intestinal bacteria in mice, additional factors not included in the model are stabilizing the system. Because we find that E. coli declines more slowly and to a higher stabilization frequency in streptomycin-treated mice, which have a more diverse flora before conventionalization, we take these results to suggest that the persistence of E. coli populations is promoted by species diversity. We propose that a mechanism for the persistence may be the presence of new E. coli niches created by keystone species in the more diverse flora.Key words: intestinal ecology, intestinal colonization, chemostat, keystone species, conventionalization.

scholarly journals Long Polar Fimbriae Contribute to Colonization by Escherichia coli O157:H7 In Vivo

2004 ◽  
Vol 72 (10) ◽  
pp. 6168-6171 ◽  
Author(s):  
Dianna M. Jordan ◽  
Nancy Cornick ◽  
Alfredo G. Torres ◽  
Evelyn A. Dean-Nystrom ◽  
James B. Kaper ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Parent Strain ◽  
Escherichia Coli O157 ◽  
Intestinal Colonization ◽  
E Coli ◽  
Gnotobiotic Piglets

ABSTRACT The contribution of long polar fimbriae to intestinal colonization by Escherichia coli O157:H7 was evaluated in sheep, conventional pigs, and gnotobiotic piglets. E. coli O157:H7 strains with lpfA1 and lpfA2 mutated were recovered in significantly lower numbers and caused fewer attachment and effacement lesions than the parent strain.

scholarly journals Estimation of Growth Rates of Escherichia coli BJ4 in Streptomycin-Treated and Previously Germfree Mice by In Situ rRNA Hybridization

1999 ◽  
Vol 6 (3) ◽  
pp. 434-436 ◽  
Author(s):  
Camilla U. Rang ◽  
Tine Rask Licht ◽  
Tore Midtvedt ◽  
Patricia L. Conway ◽  
Lin Chao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Animal Models ◽  
Growth Rates ◽  
Treated Mouse ◽  
23S Rrna ◽  
Growth Physiology ◽  
E Coli ◽  
Bacterial Growth Rates

ABSTRACT The growth physiology of Escherichia coli during colonization of the intestinal tract was studied with four animal models: the streptomycin-treated mouse carrying a reduced microflora, the monoassociated mouse with no other microflora than the introduced strain, the conventionalized streptomycin-treated mouse, and the conventionalized monoassociated mouse harboring a full microflora. A 23S rRNA fluorescent oligonucleotide probe was used for hybridization to whole E. coli cells fixed directly after being taken from the animals, and the respective growth rates of E. coli BJ4 in the four animal models were estimated by correlating the cellular concentrations of ribosomes with the growth rate of the strain. The growth rates thus estimated from the ribosomal content ofE. coli BJ4 in vivo did not differ in the streptomycin-treated and the monoassociated mice. After conventionalization there was a slight decrease of the bacterial growth rates in both animal models.

scholarly journals Role of Intimin-Tir Interactions and the Tir-Cytoskeleton Coupling Protein in the Colonization of Calves and Lambs by Escherichia coli O157:H7

2006 ◽  
Vol 74 (1) ◽  
pp. 758-764 ◽  
Author(s):  
Isabella Vlisidou ◽  
Francis Dziva ◽  
Roberto M. La Ragione ◽  
Angus Best ◽  
Junkal Garmendia ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Loop Model ◽  
Intestinal Colonization ◽  
Actin Assembly ◽  
Ileal Loop ◽  
E Coli ◽  
Coupling Protein

ABSTRACT Intimin facilitates intestinal colonization by enterohemorrhagic Escherichia coli O157:H7; however, the importance of intimin binding to its translocated receptor (Tir) as opposed to cellular coreceptors is unknown. The intimin-Tir interaction is needed for optimal actin assembly under adherent bacteria in vitro, a process which requires the Tir-cytoskeleton coupling protein (TccP/EspFU) in E. coli O157:H7. Here we report that E. coli O157:H7 tir mutants are at least as attenuated as isogenic eae mutants in calves and lambs, implying that the role of intimin in the colonization of reservoir hosts can be explained largely by its binding to Tir. Mutation of tccP uncoupled actin assembly from the intimin-Tir-mediated adherence of E. coli O157:H7 in vitro but did not impair intestinal colonization in calves and lambs, implying that pedestal formation may not be necessary for persistence. However, an E. coli O157:H7 tccP mutant induced typical attaching and effacing lesions in a bovine ligated ileal loop model of infection, suggesting that TccP-independent mechanisms of actin assembly may operate in vivo.

scholarly journals Host-specific differences in the contribution of an ESBL IncI1 plasmid to intestinal colonization by Escherichia coli O104:H4

2018 ◽  
Vol 73 (6) ◽  
pp. 1579-1585 ◽  
Author(s):  
M Giles ◽  
S A Cawthraw ◽  
M AbuOun ◽  
C M Thomas ◽  
D Munera ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Animal Species ◽  
Host Bacterium ◽  
Intestinal Colonization ◽  
Specific Pathogen Free ◽  
E Coli ◽  
New Zealand White Rabbits ◽  
Specific Pathogen ◽  
Transmission Reservoir

AbstractObjectivesTo assess stability and contribution of a large ESBL-encoding IncI1 plasmid to intestinal colonization by Escherichia coli O104:H4 in two different mammalian hosts.MethodsSpecific-pathogen-free 3–4-day-old New Zealand White rabbits and conventionally reared 6-week-old weaned lambs were orally infected with WT E. coli O104:H4 or the ESBL-plasmid-cured derivative, and the recovery of bacteria in intestinal homogenates and faeces monitored over time.ResultsCarriage of the ESBL plasmid had differing impacts on E. coli O104:H4 colonization of the two experimental hosts. The plasmid-cured strain was recovered at significantly higher levels than WT during late-stage colonization of rabbits, but at lower levels than WT in sheep. Regardless of the animal host, the ESBL plasmid was stably maintained in virtually all in vivo passaged bacteria that were examined.ConclusionsThese findings suggest that carriage of ESBL plasmids has distinct effects on the host bacterium depending upon the animal species it encounters and demonstrates that, as for E. coli O157:H7, ruminants could represent a potential transmission reservoir.

scholarly journals pH and redox dual-sensitive drug delivery system constructed based on fluorescent carbon dots

RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2656-2663
Author(s):  
Boye Zhang ◽  
Qianqian Duan ◽  
Yi Li ◽  
Jianming Wang ◽  
Wendong Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Cancer Cells ◽  
Fluorescence Imaging ◽  
Drug Delivery System ◽  
Delivery System ◽  
Carbon Dots ◽  
Ph Responsive ◽  
Charge Reversal ◽  
Fluorescent Carbon Dots

The system is pH-responsive and redox-controlled release. And the charge reversal and size transitions of the system can enhance the targeted ability. Moreover, the system can recognize the cancer cells by the fluorescence imaging.

scholarly journals Characterization and in Vivo Cloning of prlC, a Suppressor of Signal Sequence Mutations in Escherichia coli K12

Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 513-521
Author(s):  
Nancy J Trun ◽  
Thomas J Silhavy
Keyword(s):  
Escherichia Coli ◽  
Genetic Mapping ◽  
Signal Sequence ◽  
Illegitimate Recombination ◽  
Mutant Phenotype ◽  
E Coli ◽  
Physical Location ◽  
Sequence Deletion ◽  
New Alleles

ABSTRACT The prlC gene of E. coli was originally identified as an allele, prlC1, which suppresses certain signal sequence mutations in the genes for several exported proteins. We have isolated six new alleles of prlC that also confer this phenotype. These mutations can be placed into three classes based on the degree to which they suppress the lamBsignal sequence deletion, lamBs78. Genetic mapping reveals that the physical location of the mutations in prlC correlates with the strength of the suppression, suggesting that different regions of the gene can be altered to yield a suppressor phenotype. We also describe an in vivo cloning procedure using λplacMu9H. The procedure relies on transposition and illegitimate recombination to generate a specialized transducing phage that carries prlC1. This method should be applicable to any gene for which there is a mutant phenotype.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

scholarly journals Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1108
Author(s):  
Oana Craciunescu ◽  
Madalina Icriverzi ◽  
Paula Ecaterina Florian ◽  
Anca Roseanu ◽  
Mihaela Trif
Keyword(s):  
Drug Delivery ◽  
Bioactive Compounds ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Joint Disease ◽  
Duration Of Action ◽  
Immune System Activation

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

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