Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium

Microbiology ◽  
2004 ◽  
Vol 150 (4) ◽  
pp. 775-783 ◽  
Author(s):  
A. M. Prouty ◽  
I. E. Brodsky ◽  
S. Falkow ◽  
J. S. Gunn
Keyword(s):  
Salmonella Typhimurium ◽  
Bile Salt ◽  
Dna Microarray ◽  
Bile Salts ◽  
Efflux Pump ◽  
Resistance Phenotype ◽  
Ionic Detergent ◽  
Bile Resistance ◽  
Sublethal Concentrations

By DNA microarray, the Salmonella typhimurium marRAB operon was identified as being bile-activated. Transcriptional assays confirm that marRAB is activated in the presence of bile and that this response is concentration-dependent. The bile salt deoxycholate is alone able to activate transcription, while there was no response in the presence of other bile salts tested or a non-ionic detergent. Deoxycholate is able to interact with MarR and interfere with its ability to bind to the mar operator. In addition, incubation of salmonellae in the presence of sublethal concentrations of bile is able to enhance resistance to chloramphenicol and bile, by means of both mar-dependent and mar-independent pathways. To further characterize putative marRAB-regulated genes that may be important for the resistance phenotype, acrAB, which encodes an efflux pump, was analysed. In S. typhimurium, acrAB is required for bile resistance, but while transcription of acrAB is activated by bile, this activation is independent of marRAB, as well as Rob, RpoS or PhoP–PhoQ. These data suggest that bile interacts with salmonellae to increase resistance to bile and other antimicrobials and that this can occur by marRAB- and acrAB-dependent pathways that function independently with respect to bile activation.

scholarly journals Bile Salts Differentially Enhance Resistance of Enterohemorrhagic Escherichia coli O157:H7 to Host Defence Peptides

2020 ◽  
Author(s):  
Crystal Gadishaw-Lue ◽  
Alyssa Banaag ◽  
Sarah Birstonas ◽  
Aju-Sue Francis ◽  
Debora Barnett Foster
Keyword(s):  
Escherichia Coli ◽  
Small Intestine ◽  
Bile Salt ◽  
Bile Salts ◽  
Galleria Mellonella ◽  
Enterohemorrhagic Escherichia Coli ◽  
Dependent Manner ◽  
Host Defense Peptides ◽  
Resistance Phenotype ◽  
Defense Peptides

During passage through the human gastrointestinal tract, enterohemorrhagic Escherichia coli (EHEC) are exposed to membrane-damaging bile in the small intestine. We have previously reported that EHEC treatment with a physiological bile salt mixture upregulates genes encoding the two component system, basRS, and the aminoarabinose lipid A modification pathway, arnBCADTEF. The current study examines the effect of bile salt mix (BSM) treatment on EHEC resistance to three human gastrointestinal defense peptides: HD-5, HNP-1 and LL-37, as well as the role of basRS and arnT in the respective responses. After BSM-treatment, EHEC resistance to HD-5 and HNP-1 is significantly increased in a BSM-, defensin-dose dependent manner. The resistance phenotype is dependent on both basRS and arnT. However, the BSM treatment does not alter EHEC resistance to LL-37, even when the ompT gene encoding an LL-37 cleavage protease is disrupted. Interestingly, enteropathogenic E. coli, a related pathogen that infects the small intestine, shows a similar BSM-induced resistance phenotype. Using a model of EHEC infection in Galleria mellonella, we found significantly less survival of worm larvae infected with BSM-treated wild type EHEC relative to those infected with BSM-treated basS mutant, suggesting that treatment with a physiological BSM enhances virulence through a basS-mediated pathway. The results of this investigation provide persuasive evidence that bile salts typically encountered during transit through the small intestine can serve as an environmental cue for EHEC, enhancing resistance to several key host defense peptides.

scholarly journals Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump in Campylobacter jejuni

2005 ◽  
Vol 187 (21) ◽  
pp. 7417-7424 ◽  
Author(s):  
Jun Lin ◽  
Cédric Cagliero ◽  
Baoqing Guo ◽  
Yi-Wen Barton ◽  
Marie-Christine Maurel ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Conformational Changes ◽  
Bile Salts ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Dependent Manner ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Altered Expression ◽  
Bile Resistance

ABSTRACT CmeABC, a multidrug efflux pump, is involved in the resistance of Campylobacter jejuni to a broad spectrum of antimicrobial agents and is essential for Campylobacter colonization in animal intestine by mediating bile resistance. Previously, we have shown that expression of this efflux pump is under the control of a transcriptional repressor named CmeR. Inactivation of CmeR or mutation in the cmeABC promoter (P cmeABC ) region derepresses cmeABC, leading to overexpression of this efflux pump. However, it is unknown if the expression of cmeABC can be conditionally induced by the substrates it extrudes. In this study, we examined the expression of cmeABC in the presence of various antimicrobial compounds. Although the majority of the antimicrobials tested did not affect the expression of cmeABC, bile salts drastically elevated the expression of this efflux operon. The induction was observed with both conjugated and unconjugated bile salts and was in a dose- and time-dependent manner. Experiments using surface plasmon resonance demonstrated that bile salts inhibited the binding of CmeR to P cmeABC , suggesting that bile compounds are inducing ligands of CmeR. The interaction between bile salts and CmeR likely triggers conformational changes in CmeR, resulting in reduced binding affinity of CmeR to P cmeABC . Bile did not affect the transcription of cmeR, indicating that altered expression of cmeR is not a factor in bile-induced overexpression of cmeABC. In addition to the CmeR-dependent induction, some bile salts (e.g., taurocholate) also activated the expression of cmeABC by a CmeR-independent pathway. Consistent with the elevated production of CmeABC, the presence of bile salts in culture media resulted in increased resistance of Campylobacter to multiple antimicrobials. These findings reveal a new mechanism that modulates the expression of cmeABC and further support the notion that bile resistance is a natural function of CmeABC.

The human bile salt sodium deoxycholate induces metabolic and cell envelope changes in Salmonella Typhi leading to bile resistance

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Isaac B. Olivar-Casique ◽  
Liliana Medina-Aparicio ◽  
Selena Mayo ◽  
Yitzel Gama-Martínez ◽  
Javier E. Rebollar-Flores ◽  
...  
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Cell Envelope ◽  
Sodium Deoxycholate ◽  
Salmonella Typhi ◽  
Metabolic Adaptation ◽  
Human Bile ◽  
Content Type ◽  
Genetic Elements ◽  
Bile Resistance

Introduction. Salmonella enterica serovar Typhi (S. Typhi) is the etiological agent of typhoid fever. To establish an infection in the human host, this pathogen must survive the presence of bile salts in the gut and gallbladder. Hypothesis. S. Typhi uses multiple genetic elements to resist the presence of human bile. Aims. To determine the genetic elements that S. Typhi utilizes to tolerate the human bile salt sodium deoxycholate. Methodology. A collection of S. Typhi mutant strains was evaluated for their ability to growth in the presence of sodium deoxycholate and ox-bile. Additionally, transcriptomic and proteomic responses elicited by sodium deoxycholate on S. Typhi cultures were also analysed. Results. Multiple transcriptional factors and some of their dependent genes involved in central metabolism, as well as in cell envelope, are required for deoxycholate resistance. Conclusion. These findings suggest that metabolic adaptation to bile is focused on enhancing energy production to sustain synthesis of cell envelope components exposed to damage by bile salts.

scholarly journals Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Kourtney P. Nickerson ◽  
Rachael B. Chanin ◽  
Jeticia R. Sistrunk ◽  
David A. Rasko ◽  
Peter J. Fink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Salt ◽  
Biofilm Formation ◽  
Bile Salts ◽  
Efflux Pump ◽  
Shigella Flexneri ◽  
Growth Patterns ◽  
Transcriptional Profile ◽  
Sequencing Analysis ◽  
Content Type

ABSTRACT The Shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. While many aspects of Shigella colonic cell invasion are known, crucial gaps in knowledge regarding how the bacteria survive, transit, and regulate gene expression prior to infection remain. In this study, we define mechanisms of resistance to bile salts and build on previous research highlighting induced virulence in Shigella flexneri strain 2457T following exposure to bile salts. Typical growth patterns were observed within the physiological range of bile salts; however, growth was inhibited at higher concentrations. Interestingly, extended periods of exposure to bile salts led to biofilm formation, a conserved phenotype that we observed among members of the Enterobacteriaceae. Characterization of S. flexneri 2457T biofilms determined that both bile salts and glucose were required for formation, dispersion was dependent upon bile salts depletion, and recovered bacteria displayed induced adherence to HT-29 cells. RNA-sequencing analysis verified an important bile salt transcriptional profile in S. flexneri 2457T, including induced drug resistance and virulence gene expression. Finally, functional mutagenesis identified the importance of the AcrAB efflux pump and lipopolysaccharide O-antigen synthesis for bile salt resistance. Our data demonstrate that S. flexneri 2457T employs multiple mechanisms to survive exposure to bile salts, which may have important implications for multidrug resistance. Furthermore, our work confirms that bile salts are important physiological signals to activate S. flexneri 2457T virulence. This work provides insights into how exposure to bile likely regulates Shigella survival and virulence during host transit and subsequent colonic infection.

scholarly journals Role of the HefC Efflux Pump inHelicobacter pyloriCholesterol-Dependent Resistance to Ceragenins and Bile Salts

2010 ◽  
Vol 79 (1) ◽  
pp. 88-97 ◽  
Author(s):  
Elizabeth A. Trainor ◽  
Katherine E. Horton ◽  
Paul B. Savage ◽  
Traci L. Testerman ◽  
David J. McGee
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Efflux Pump ◽  
Critical Role ◽  
Defined Medium ◽  
Antibacterial Compounds ◽  
The Two Cultures ◽  
H Pylori ◽  
Cholesterol Modification

ABSTRACTThe human gastric pathogenHelicobacter pylorimodifies host cholesterol via glycosylation and incorporates the glycosylated cholesterol into its membrane; however, the benefits of cholesterol toH. pyloriare largely unknown. We speculated that cholesterol in theH. pylorimembrane might alter the susceptibility of these organisms to membrane-disrupting antibacterial compounds. To test this hypothesis,H. pyloristrains were cultured in Ham's F-12 chemically defined medium in the presence or absence of cholesterol. The two cultures were subjected to overnight incubations with serial 2-fold dilutions of 10 bile salts and four ceragenins, which are novel bile salt derivatives that mimic membrane-disrupting activity of antimicrobial peptides.H. pyloricultured with cholesterol was substantially more resistant to seven of the bile salts and three ceragenins thanH. pyloricultured without cholesterol. In most cases, these cholesterol-dependent differences ranged from 2 to 7 orders of magnitude; this magnitude depended on concentration of the agent. Cholesterol is modified by glycosylation using Cgt, a cholesteryl glycosyltransferase. Surprisingly, acgtknockout strain still maintained cholesterol-dependent resistance to bile salts and ceragenins, indicating that cholesterol modification was not involved in resistance. We then tested whether three putative, paralogous inner membrane efflux pumps, HefC, HefF, or HefI, played a role. While HefF and HefI appeared unimportant, HefC was shown to play a critical role in the resistance to bile salts and ceragenins by multiple methods in multiple strain backgrounds. Thus, both cholesterol and the putative bile salt efflux pump HefC play important roles inH. pyloriresistance to bile salts and ceragenins.

scholarly journals Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae

2012 ◽  
Vol 56 (8) ◽  
pp. 4450-4458 ◽  
Author(s):  
Mark Veleba ◽  
Paul G. Higgins ◽  
Gerardo Gonzalez ◽  
Harald Seifert ◽  
Thamarai Schneiders
Keyword(s):  
Multidrug Resistance ◽  
Klebsiella Pneumoniae ◽  
Efflux Pump ◽  
Content Type ◽  
Resistance Phenotype ◽  
Serratia Proteamaculans ◽  
Virulence Potential ◽  
Article Type ◽  
Acrab Efflux Pump

ABSTRACTTranscriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes.Klebsiella pneumoniaeis a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription oframAis associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466–4467, 2012). Bioinformatic analyses of the availableKlebsiellagenome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded inK. pneumoniae,Enterobactersp. 638,Serratia proteamaculans568, andEnterobacter cloacae. We show that the overexpression ofrarAresults in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show thatrarA(MGH 78578 KPN_02968) and its neighboring efflux pump operonoqxAB(KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest thatrarAoverexpression upregulates theoqxABefflux pump. Additionally, it appears thatoqxR, encoding a GntR-type regulator adjacent to theoqxABoperon, is able to downregulate the expression of theoqxABefflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.

scholarly journals STUDI VIABILITAS ISOLAT BAKTERI ASAM LAKTAT YANG DIISOLASI DARI ASINAN REBUNG BAMBU TABAH TERHADAP pH RENDAH DAN GARAM EMPEDU

2019 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Nurul Octavia Wasis ◽  
Nyoman Semadi Antara ◽  
Ida Bagus Wayan Gunam
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Bile Salt ◽  
Bile Salts ◽  
Salt Resistance ◽  
Low Ph ◽  
Fermented Food ◽  
Bamboo Shoot ◽  
Probiotic Lactic Acid Bacteria ◽  
Mrs Broth

Tabah bamboo shoot pickle is one of the fermented food which is the source of lactic acid bacteria.  Lactic acid bacteria (LAB) is beneficial to health because it has the ability as a probiotic. Lactic acid bacteria that have probiotic criteria should have resistance to low pH and bile salts. This study aims to determine isolates of lactic acid bacteria isolated from tabah bamboo shoot pickle resistant to low pH and bile salts (NaDC). Lactic acid bacteria were tested to low pH by using MRS broth that have different pH (pH 2, pH 3, pH 4 and pH 6.2 as a control) incubated at 37ºC for 3 hours. isolates were survive in low pH then continued in bile salt resistance test with 0.3% bile salt concentration for 15 minutes, 30 minutes, 45 minutes, 60 minutes and 24 hours. The results showed that three isolates out of 88 isolates had ability to grow in low pH and in medium supplemented by NaDC 0,3%. The isolates are AR 3057, AR 3101 and AR 6152 which can be used as candidat of  probiotic. Keywords : Tabah bamboo shoot pickle, lactic acid bacteria, probiotic, low pH, bile salt

scholarly journals Regulation of mdr2 P-glycoprotein expression by bile salts

1997 ◽  
Vol 321 (2) ◽  
pp. 389-395 ◽  
Author(s):  
Charles M. G. FRIJTERS ◽  
Roelof OTTENHOFF ◽  
Michel J. A. van WIJLAND ◽  
Carin M. J. van NIEUWKERK ◽  
Albert K. GROEN ◽  
...  
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Control Diet ◽  
Mrna Level ◽  
Northern Blotting ◽  
Mrna Levels ◽  
Male Mice ◽  
Complete Replacement ◽  
P Glycoprotein ◽  
Mrna Content

The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the canalicular membrane of the mouse hepatocyte is a rate-controlling step in the biliary secretion of phospholipid. Since bile salts also regulate the secretion of biliary lipids, we investigated the influence of the type of bile salt in the circulation on mdr2 Pgp expression and activity. Male mice were fed a purified diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added. This led to a near-complete replacement of the endogenous bile salt pool (mainly tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The phospholipid secretion capacity was then determined by infusion of increasing amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in maximal phospholipid secretion compared with that in mice on the control diet. Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by 42%. Feeding with ursodeoxycholate did not influence the maximum rate of phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2 Pgp mRNA level than male mice, and this was also correlated with a higher phospholipid secretion capacity. This could be explained by the 4-fold higher basal cholate content in the bile of female compared with male mice. Our results suggest that the type of bile salts in the circulation influences the expression of the mdr2 gene.

scholarly journals Characteristics of bile salt uptake into skate hepatocytes

1994 ◽  
Vol 299 (3) ◽  
pp. 665-670 ◽  
Author(s):  
G Fricker ◽  
V Dubost ◽  
K Finsterwald ◽  
J L Boyer
Keyword(s):  
Substrate Specificity ◽  
Bile Salt ◽  
Transport System ◽  
Bile Salts ◽  
Organic Anion ◽  
Anion Transport ◽  
Organic Anion Transport ◽  
Salt Uptake ◽  
Anion Transport System ◽  
Alpha 7

The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+)-independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non-competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts.

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