scholarly journals Cultivation and Genomic Characterization of the Bile Bacterial Species From Cholecystitis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiulong Yan ◽  
Siyi Zhang ◽  
Shenghui Li ◽  
Guangyang Wang ◽  
Aiqin Zhang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Bacterial Species ◽  
Fluoroquinolone Resistance ◽  
Metagenomic Sequencing ◽  
Multidrug Resistance Proteins ◽  
Aminoglycoside Resistance ◽  
Human Bile ◽  
Resistance Proteins ◽  
Bile Bacteria

The microbes in human bile are closely related to gallbladder health and other potential disorders. Although the bile microbial community has been investigated by recent studies using amplicon or metagenomic sequencing technologies, the genomic information of the microbial species resident in bile is rarely reported. Herein, we isolated 138 bacterial colonies from the fresh bile specimens of four cholecystitis patients using a culturome approach and genomically characterized 35 non-redundant strains using whole-genome shotgun sequencing. The bile bacterial isolates spanned 3 classes, 6 orders, 10 families, and 14 genera, of which the members of Enterococcus, Escherichia–Shigella, Lysinibacillus, and Enterobacter frequently appeared. Genomic analysis identified three species, including Providencia sp. D135, Psychrobacter sp. D093, and Vibrio sp. D074, which are not represented in existing reference genome databases. Based on the genome data, the functional capacity between bile and gut isolates was compared. The bile strains encoded 5,488 KEGG orthologs, of which 4.9% were specific to the gut strains, including the enzymes involved in biofilm formation, two-component systems, and quorum-sensing pathways. A total of 472 antibiotic resistance genes (ARGs) were identified from the bile genomes including multidrug resistance proteins (42.6%), fluoroquinolone resistance proteins (12.3%), aminoglycoside resistance proteins (9.1%), and β-lactamase (7.2%). Moreover, in vitro experiments showed that some bile bacteria have the capabilities for bile salt deconjugation or biotransformation (of primary bile acids into secondary bile acids). Although the physiological or pathological significance of these bacteria needs further exploration, our works expanded knowledge about the genome, diversity, and function of human bile bacteria.

scholarly journals Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

2021 ◽  
Vol 12 ◽  
Author(s):  
José Pedro Gil ◽  
Cláudia Fançony
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Multi Drug Resistance ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Diverse Groups ◽  
Endogenous Substances

The capacity of the lethal Plasmodium falciparum parasite to develop resistance against anti-malarial drugs represents a central challenge in the global control and elimination of malaria. Historically, the action of drug transporters is known to play a pivotal role in the capacity of the parasite to evade drug action. MRPs (Multidrug Resistance Protein) are known in many phylogenetically diverse groups to be related to drug resistance by being able to handle a large range of substrates, including important endogenous substances as glutathione and its conjugates. P. falciparum MRPs are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment. Information on P. falciparum MRPs is scattered in the literature, with no specialized review available. We herein address this issue by reviewing the present state of knowledge.

Transmembrane Transport of Endo- and Xenobiotics by Mammalian ATP-Binding Cassette Multidrug Resistance Proteins

2006 ◽  
Vol 86 (3) ◽  
pp. 849-899 ◽  
Author(s):  
Roger G. Deeley ◽  
Christopher Westlake ◽  
Susan P. C. Cole
Keyword(s):  
Multidrug Resistance ◽  
Alkylating Agents ◽  
Structural Features ◽  
Atp Binding ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Wide Range ◽  
Atp Binding Cassette

Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) comprise the 13 members of the human “C” branch of the ATP binding cassette (ABC) superfamily. All C branch proteins share conserved structural features in their nucleotide binding domains (NBDs) that distinguish them from other ABC proteins. The MRPs can be further divided into two subfamilies “long” (MRP1, -2, -3, -6, and -7) and “short” (MRP4, -5, -8, -9, and -10). The short MRPs have a typical ABC transporter structure with two polytropic membrane spanning domains (MSDs) and two NBDs, while the long MRPs have an additional NH2-terminal MSD. In vitro, the MRPs can collectively confer resistance to natural product drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and, under certain circumstances, alkylating agents. The MRPs are also primary active transporters of other structurally diverse compounds, including glutathione, glucuronide, and sulfate conjugates of a large number of xeno- and endobiotics. In vivo, several MRPs are major contributors to the distribution and elimination of a wide range of both anticancer and non-anticancer drugs and metabolites. In this review, we describe what is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates. We also summarize knowledge of their possible physiological functions and evidence that they may be involved in the clinical drug resistance of various forms of cancer.

Mammalian multidrug-resistance proteins (MRPs)

2011 ◽  
Vol 50 ◽  
pp. 179-207 ◽  
Author(s):  
Andrew J. Slot ◽  
Steven V. Molinski ◽  
Susan P.C. Cole
Keyword(s):  
Multidrug Resistance ◽  
Gene Knockout ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Gene Knockout Mice ◽  
Membrane Spanning ◽  
Endogenous Metabolites ◽  
Membrane Spanning Domains

Subfamily C of the human ABC (ATP-binding cassette) superfamily contains nine proteins that are often referred to as the MRPs (multidrug-resistance proteins). The ‘short’ MRP/ABCC transporters (MRP4, MRP5, MRP8 and ABCC12) have a typical ABC structure with four domains comprising two membrane-spanning domains (MSD1 and MSD2) each followed by a nucleotide-binding domain (NBD1 and NBD2). The ‘long’ MRP/ABCCs (MRP1, MRP2, MRP3, ABCC6 and MRP7) have five domains with the extra domain, MSD0, at the N-terminus. The proteins encoded by the ABCC6 and ABCC12 genes are not known to transport drugs and are therefore referred to as ABCC6 and ABCC12 (rather than MRP6 and MRP9) respectively. A large number of molecules are transported across the plasma membrane by the MRPs. Many are organic anions derived from exogenous sources such as conjugated drug metabolites. Others are endogenous metabolites such as the cysteinyl leukotrienes and prostaglandins which have important signalling functions in the cell. Some MRPs share a degree of overlap in substrate specificity (at least in vitro), but differences in transport kinetics are often substantial. In some cases, the in vivo substrates for some MRPs have been discovered aided by studies in gene-knockout mice. However, the molecules that are transported in vivo by others, including MRP5, MRP7, ABCC6 and ABCC12, still remain unknown. Important differences in the tissue distribution of the MRPs and their membrane localization (apical in contrast with basolateral) in polarized cells also exist. Together, these differences are responsible for the unique pharmacological and physiological functions of each of the nine ABCC transporters known as the MRPs.

scholarly journals Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 708
Author(s):  
Susbin Raj Wagle ◽  
Bozica Kovacevic ◽  
Daniel Walker ◽  
Corina Mihaela Ionescu ◽  
Melissa Jones ◽  
...  
Keyword(s):  
Drug Release ◽  
Bile Acids ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Lithocholic Acid ◽  
Ex Vivo ◽  
Biological Effects ◽  
Drug Formulation ◽  
Human Bile

Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor gut absorption after an oral dose, which necessitates the administration of high doses and causes subsequent side effects. Probucol (PB) is a highly lipophilic drug with poor oral absorption that resulted in restrictions on its clinical prescribing. Hence, this study aimed to design new delivery systems for PB using ULCA-based matrices and to test drug formulation, release, temperature, and biological effects. ULCA-based matrices were formulated for PB oral delivery by applying the jet-flow microencapsulation technique using sodium alginate as a polymer. ULCA addition to new PB matrices improved the microcapsule’s stability, drug release in vitro (formulation study), and showed a promising effect in ex vivo study (p < 0.05), suggesting that ULCA can optimize the oral delivery of PB and support its potential application in diabetes treatment.

scholarly journals Biotic Interactions Shape the Ecological Distributions ofStaphylococcusSpecies

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Erik K. Kastman ◽  
Noelani Kamelamela ◽  
Josh W. Norville ◽  
Casey M. Cosetta ◽  
Rachel J. Dutton ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Biotic Interactions ◽  
Integrated Approach ◽  
Comparative Genomic ◽  
Coagulase Negative Staphylococcus ◽  
Metagenomic Sequencing ◽  
Tract Infections

ABSTRACTMany metagenomic sequencing studies have observed the presence of closely related bacterial species or genotypes in the same microbiome. Previous attempts to explain these patterns of microdiversity have focused on the abiotic environment, but few have considered how biotic interactions could drive patterns of microbiome diversity. We dissected the patterns, processes, and mechanisms shaping the ecological distributions of three closely relatedStaphylococcusspecies in cheese rind biofilms. Paradoxically, the most abundant species (S. equorum) is the slowest colonizer and weakest competitor based on growth and competition assays in the laboratory. Throughin vitrocommunity reconstructions, we determined that biotic interactions with neighboring fungi help resolve this paradox. Species-specific stimulation of the poor competitor by fungi of the genusScopulariopsisallowsS. equorumto dominate communitiesin vitroas it doesin situ. Results of comparative genomic and transcriptomic experiments indicate that iron utilization pathways, including a homolog of theS. aureusstaphyloferrin B siderophore operon pathway, are potential molecular mechanisms underlyingStaphylococcus-Scopulariopsisinteractions. Our integrated approach demonstrates that fungi can structure the ecological distributions of closely related bacterial species, and the data highlight the importance of bacterium-fungus interactions in attempts to design and manipulate microbiomes.IMPORTANCEDecades of culture-based studies and more recent metagenomic studies have demonstrated that bacterial species in agriculture, medicine, industry, and nature are unevenly distributed across time and space. The ecological processes and molecular mechanisms that shape these distributions are not well understood because it is challenging to connectin situpatterns of diversity with mechanisticin vitrostudies in the laboratory. Using tractable cheese rind biofilms and a focus on coagulase-negative staphylococcus (CNS) species, we demonstrate that fungi can mediate the ecological distributions of closely related bacterial species. One of theStaphylococcusspecies studied,S. saprophyticus, is a common cause of urinary tract infections. By identifying processes that control the abundance of undesirable CNS species, cheese producers will have more precise control on the safety and quality of their products. More generally,Staphylococcusspecies frequently co-occur with fungi in mammalian microbiomes, and similar bacterium-fungus interactions may structure bacterial diversity in these systems.

Effect of bile and bile acids on binding of intrinsic factor to cobalamin and intrinsic factor-cobalamin complex to ileal receptor

1983 ◽  
Vol 245 (1) ◽  
pp. G72-G77
Author(s):  
B. Seetharam ◽  
M. Jimenez ◽  
D. H. Alpers
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intrinsic Factor ◽  
Binding Ability ◽  
Human Bile ◽  
Receptor Molecule ◽  
Protease Digestion ◽  
Normal Absorption

Human bile or commercially available bile acids bind [57Co]cobalamin (Cbl) due to the presence of "R"-type binders, which are normally present in the former and present as a contaminant in the latter. The competition of these R proteins for the binding of Cbl by intrinsic factor (IF) could explain the in vivo inhibition attributed previously to the bile acids themselves. R protein seems to be involved in the inhibition of Cbl binding because protease digestion of either bile or bile acid abolishes the Cbl binding ability. Moreover, antibody to R protein abolishes the inhibition. Bile or bile acids do not have a direct effect on either purified IF or the IF-Cbl receptor molecule, even though bile acids increase the attachment of IF-[57Co]Cbl to ileal brush-border membranes. These data demonstrate two steps where components of bile could affect Cbl absorption: the binding of Cbl to IF and of IF-Cbl to its ileal receptor. It is not clear whether these in vitro phenomena are important for the normal absorption of Cbl in vivo.

scholarly journals Characterization of Mycoplasma hominis mutations involved in resistance to fluoroquinolones.

1997 ◽  
Vol 41 (2) ◽  
pp. 269-273 ◽  
Author(s):  
C M Bebear ◽  
J M Bové ◽  
C Bebear ◽  
J Renaudin
Keyword(s):  
Reference Strain ◽  
Bacterial Species ◽  
Mycoplasma Hominis ◽  
Base Change ◽  
Fluoroquinolone Resistance ◽  
Genes Encoding ◽  
One Step ◽  
Resistant Mutants ◽  
High Level

Fluoroquinolone-resistant mutants of Mycoplasma hominis were selected in vitro from the PG21 susceptible reference strain either by multistep selection on increasing concentrations of various fluoroquinolones or by one-step selection on agar medium with ofloxacin. The quinolone resistance-determining regions (QRDR) of the structural genes encoding the A and b subunits of DNA gyrase were amplified by PCR, and the nucleotide sequences of eight multistep-selected resistant strains were compared to those of susceptible strain PG21. Four high-level resistant mutants that were selected on norfloxacin or ofloxacin contained a C-to-T transition in the gyrA QRDR, leading to substitution of Ser-83 by Leu in the GyrA protein. Analysis of the sequence of the gyrB QRDR of the eight multistep-selected mutants did not reveal any difference compared to that of the gyrB QRDR of the reference strain M. hominis PG21. Similar analyses of eight one-step-selected mutants did not reveal any base change in the gyrA and gyrB QRDRs. These results suggest that in M. hominis, like in other bacterial species, a gyrA mutation at Ser-83 is associated with fluoroquinolone resistance.

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