Toxin Precursors Research Articles

Isomaltodextrin inhibits kidney enlargement induced by a high-protein diet through its metabolism by gut microbiota.

To evaluate the effects of the soluble fiber isomaltodextrin in a protein-biased diet, a 21-day protein diet trial was conducted in rats, with 60% of the calories derived from protein. The results revealed that the high-protein diet alone led to a significant increase in kidney weight. In contrast, the consumption of water with 5% isomaltodextrin dissolved in it, along with a high-protein diet, suppressed this weight gain. To elucidate this mechanism, an analysis of serum urea toxins confirmed that the concentrations of phenyl sulfate were significantly higher with high protein, and significantly lower with isomaltodextrin. The impact of a high-protein on increased phenol in cecal contents, an increased that was mitigated by the isomaltodextrin. This suggests that the inhibitory effect of isomaltodextrin on renal hypertrophy was due to the suppression of urea toxin precursor production by the gut microbiota.

The Effect of Renaltec on Serum Uremic Toxins in Cats with Experimentally Induced Chronic Kidney Disease.

Serum uremic toxins markedly increase in cats with chronic kidney disease (CKD) and have deleterious consequences. Renaltec is an oral adsorbent that binds uremic toxin precursors in the gut. In this prospective cohort study utilizing 13 purpose-bred cats with remnant kidney model-induced CKD (12 IRIS Stage 2, 1 IRIS Stage 3) eating a standardized renal diet, we aimed to assess the effect of Renaltec administration on serum indoxyl sulfate (IDS) and p-cresol sulfate (pCS) concentrations. Cats were sequentially treated with standard of care for 56 days, 500 mg Renaltec orally once daily for 56 days, and then three months later, 500 mg Renaltec orally twice daily for 56 days. Serum IDS and pCS concentrations were measured 28 and 56 days after the administration of Renaltec. Blood pressure and kidney function were measured before and 56 days after the administration of Renaltec. Significant decreases in serum IDS and pCS concentrations were observed for both once- and twice-daily dosing, particularly during the first 28 days of administration. More cats with BID dosing had clinically significant reductions in serum IDS and pCS concentrations than with SID dosing. Renaltec can reduce the serum concentrations of deleterious gut-derived uremic toxins in cats with CKD.

Rational Engineering of Escherichia coli Nissle 1917 as Live Biotherapeutic to Degrade Uremic Toxin Precursors.

Uremic toxins (UTs) are microbiota-derived metabolites that accelerate the progression of kidney damage in patients with chronic kidney disease (CKD). One of the major UTs involved in CKD progression is p-cresol-sulfate (PCS), derived from dietary l-tyrosine (l-Tyr). Here, we engineered a probiotic strain of Escherichia coli Nissle 1917, to convert l-Tyr to the nontoxic compound p-coumaric acid via tyrosine ammonia lyase (TAL). First, a small metagenomic library was assessed to identify the TAL with the greatest whole-cell activity. Second, accessory genes implicated in the import of l-Tyr and export of PCA were overexpressed to enhance l-Tyr degradation by 106% and 56%, respectively. Last, random mutagenesis coupled to a novel selection and screening strategy was developed that identified a TAL variant with a 25% increase in whole-cell activity. Taken together, the final strain exhibits a 183% improvement over initial whole-cell activity and provides a promising candidate to degrade l-Tyr mediated PCS accumulation.

Pathogenicity of monokaryotic and dikaryotic mycelia of Ganoderma boninense revealed via LC–MS-based metabolomics

This study compared the pathogenicity of monokaryotic (monokaryon) and dikaryotic (dikaryon) mycelia of the oil palm pathogen Ganoderma boninense via metabolomics approach. Ethyl acetate crude extracts of monokaryon and dikaryon were analysed by liquid chromatography quadrupole/time-of-flight-mass spectrometry (LC-Q/TOF–MS) coupled with multivariate data analysis using MetaboAnalyst. The mummichog algorithm was also used to identify the functional activities of monokaryon and dikaryon without a priori identification of all their secondary metabolites. Results revealed that monokaryon produced lesser fungal metabolites than dikaryon, suggesting that monokaryon had a lower possibility of inducing plant infection. These findings were further supported by the identified functional activities. Monokaryon exhibits tyrosine, phenylalanine, and tryptophan metabolism, which are important for fungal growth and development and to produce toxin precursors. In contrast, dikaryon exhibits the metabolism of cysteine and methionine, arginine and proline, and phenylalanine, which are important for fungal growth, development, virulence, and pathogenicity. As such, monokaryon is rendered non-pathogenic as it produces growth metabolites and toxin precursors, whereas dikaryon is pathogenic as it produces metabolites that are involved in fungal growth and pathogenicity. The LC–MS-based metabolomics approach contributes significantly to our understanding of the pathogenesis of Ganoderma boninense, which is essential for disease management in oil palm plantations.

Structural basis of the activation of MARTX cysteine protease domain from Vibrio vulnificus.

The multifunctional autoprocessing repeat-in-toxin (MARTX) toxin is the primary virulence factor of Vibrio vulnificus displaying cytotoxic and hemolytic properties. The cysteine protease domain (CPD) is responsible for activating the MARTX toxin by cleaving the toxin precursor and releasing the mature toxin fragments. To investigate the structural determinants for inositol hexakisphosphate (InsP6)-mediated activation of the CPD, we determined the crystal structures of unprocessed and β-flap truncated MARTX CPDs of Vibrio vulnificus strain MO6-24/O in complex with InsP6 at 1.3 and 2.2Å resolution, respectively. The CPD displays a conserved domain with a central seven-stranded β-sheet flanked by three α-helices. The scissile bond Leu3587-Ala3588 is bound in the catalytic site of the InsP6-loaded form of the Cys3727Ala mutant. InsP6 interacts with the conserved basic cleft and the β-flap inducing the active conformation of catalytic residues. The β-flap of the post-CPD is flexible in the InsP6-unbound state. The structure of the CPD Δβ-flap showed an inactive conformation of the catalytic residues due to the absence of interaction between the active site and the β-flap. This study confirms the InsP6-mediated activation of the MARTX CPDs in which InsP6-binding induces conformational changes of the catalytic residues and the β-flap that holds the N terminus of the CPD in the active site, facilitating hydrolysis of the scissile bond.

Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota

Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.

Association between Dental Scores and Saliva Uremic Toxins.

Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A total of 88 patients were included in the study, with chronic kidney disease stage 2 to 5 (without kidney replacement). We analysed the total concentrations of eight uremic toxins (trimethylamine N-oxide -TMAO-, Indoxyl Sulfate, P-cresyl-sulfate, Indole 3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid -CMPF-, Kynurenine, Hippuric acid and Phenylacetylglutamine) and three precursors of uremic toxins (Tyrosine, Phenylalanine and Tryptophan) in the saliva using LC-MS/MS. We observed, for the first time, the association between various dental scores: DMFT, FST, CPITN, and OHIS, and saliva uremic toxins and precursors: TMAO, indoxyl sulfate, or hippuric acid. Further prospective interventional studies are required to confirm our results.

Comparing two strategies of counter-defense against plant toxins: a modeling study on plant–herbivore interactions

IntroductionVarious herbivorous insects prefer toxic plants as their hosts, although this may appear paradoxical. They have evolved specific adaptations (called counter-defenses) against the toxins. For example, the two-component chemical defense system of plants of the Brassicaceae family against herbivores consists of glucosinolates (GLSs) and the activating enzyme myrosinase. GLS hydrolysis by myrosinase leads to isothiocyanates (ITCs), which are toxic and deterrent to many insect herbivores. Two different types of counter-defenses can be distinguished: a preemptive counter-defense that prevents the GLSs from being hydrolyzed to ITCs due to metabolic redirection and direct counter-defense, where the ITCs are formed but then metabolized to non-toxic conjugates. In general, preemptive counter-defense is only a possibility if the plant stores a precursor of the toxin, which is activated upon attack. Preemptive counter-defense is believed to be more efficient due to the lower exposure to ITCs, but this has not been satisfactorily demonstrated experimentally.MethodsHere, we derive on theoretical grounds the conditions under which preemptive counter-defense reduces exposure to ITCs compared to direct counter-defense by studying the dynamics of GLS defense and counter-defense with two separate ordinary differential equation models. We model how herbivory transfers the GLSs to the insect gut with the leaf material. Thereafter, we describe the insects’ exposure to toxins by deriving the dynamics of ITCs in the gut during feeding with the two types of counter-defenses.Results and discussionBy calculating the area under the curve (AUC) of the ITC concentrations, we show, based on empirical data, that herbivores with a preemptive detoxification system are usually less exposed to ITCs. In addition, our models explain how the decline in the level of ITCs is achieved by both counter-defenses, which helps to understand the overall mechanisms and benefits of these techniques. Our results may also apply to plant defenses by inactive toxin precursors other than GLSs as well as to insects that sequester such precursors for their own defense.

Efficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment

Indoxyl sulfate is a protein-bound uremic toxin synthesized from indole that cannot be efficiently removed by the hemodialysis method and thus becomes a key risk factor for the progression of chronic kidney disease. Here, we develop a non-dialysis treatment strategy to fabricate an ultramicroporous olefin-linked covalent organic framework with high crystallinity in a green and scalable fashion for selectively removing the indoxyl sulfate precursor (i.e., indole) from the intestine. Various analyses show that the resulting material exhibits excellent gastrointestinal fluid stability, high adsorption efficiency, and good biocompatibility. Notably, it realizes the efficient and selective removal of indole from the intestine and significantly attenuates serum indoxyl sulfate level in vivo. More importantly, the selective removal efficacy of indole is substantially higher than that of the commercial adsorbent AST-120 used in the clinic. The present study opens up a new avenue to eliminate indoxyl sulfate by a non-dialysis strategy and further expands the in vivo applications of covalent organic frameworks.

New realtime PCR method development for detection and quantification of Bacillus subtilis

Bacillus subtilis is a widely used bacterial strain in probiotic production. The strains belong to this species are endosporogenic, tolerant to acidic pH conditions in the stomach, and many have been shown to produce enzymes that aid in food digestion and inhibit pathogenic microorganisms. In this study, a detection and qualitification method was developed based on amplification of aprE gene ultilising realtime PCR. The aprE target gene encodes subtilisin toxin precursor and is a highly conservative and specific gene of B. subtilis. The method yielded high sensitivity with LOD is 102 (CFU/mL), LOQ is 102 (CFU/mL), specificity, and accuracy are both 100%. The preparatory tools were constructed using cycle threshold (Ct) compare with B. subtilis concentration, which showed linear correlation (R2 = 1, slope = - 3.584).

Equipped for Sexual Stings? Male-Specific Venom Peptides in Euscorpius italicus.

In the animal kingdom, intraspecific variation occurs, for example, between populations, different life stages, and sexes. For venomous animals, this can involve differences in their venom composition. In cases where venom is utilized in the context of mating, the differences in composition might be driven by sexual selection. In this regard, the genus Euscorpius is a promising group for further research, as some of these scorpions exhibit a distinct sexual dimorphism and are known to perform a sexual sting during mating. However, the venom composition of this genus remains largely unexplored. Here, we demonstrate that Euscorpius italicus exhibits a male-specific venom composition, and we identify a large fraction of the substances involved. The sex specificity of venom peptides was first determined by analyzing the presence/absence patterns of ion signals in MALDI-TOF mass spectra of venom samples from both sexes and juveniles. Subsequently, a proteo-transcriptomic analysis provided sequence information on the relevant venom peptides and their corresponding precursors. As a result, we show that several potential toxin precursors are down-regulated in male venom glands, possibly to reduce toxic effects caused to females during the sexual sting. We have identified the precursor of one of the most prominent male-specific venom peptides, which may be an ideal candidate for activity tests in future studies. In addition to the description of male-specific features in the venom of E. italicus, this study also includes a general survey of venom precursors in this species.

Decreasing microbiota-derived uremic toxins to improve CKD outcomes

Chronic kidney disease (CKD) is set to become the fifth-leading global cause of death by 2040. This illustrates the many unknowns regarding its pathogenesis and therapy. A key unknown relates to the therapeutic impact of the interaction between CKD and the gut microbiome. The normal gut microbiome is essential for body homeostasis. There is evidence for multiple interactions between the microbiota and CKD-its causes, comorbidities and therapeutic interventions-that are only starting to be unraveled. Thus uremic retention products, such as urea itself, modify the gut microbiota biology and both dietary and drug prescriptions modify the composition and function of the microbiota. Conversely, the microbiota may influence the progression and manifestations of CKD through the production of biologically active compounds (e.g. short-chain fatty acids such as butyrate and crotonate) and precursors of uremic toxins. The present review addresses these issues and their relevance for novel therapeutic approaches ranging from dietary interventions to prebiotics, probiotics, synbiotics and postbiotics, to the prevention of the absorption of microbial metabolites and to increased clearance of uremic toxins of bacterial origin through optimized dialysis techniques or blockade of tubular cell transporters.

Expression of the K74 Killer Toxin from Saccharomyces paradoxus Is Modulated by the Toxin-Encoding M74 Double-Stranded RNA 5′ Untranslated Terminal Region

Yeast killer toxins are widely distributed in nature, conferring a competitive advantage to the producer yeasts over nonkiller ones when nutrients are scarce. Most of these toxins are encoded on double-stranded RNAs (dsRNAs) generically called M. L-A members of the viral family Totiviridae act as helper viruses to maintain M, providing the virion proteins that separately encapsidate and replicate L-A and M genomes. M genomes are organized in three regions, a 5' region coding the preprotoxin, followed by an internal poly(A) stretch and a 3' noncoding region. In this work, we report the characterization of K74 toxin encoded on M74 dsRNA from Saccharomyces paradoxus Q74.4. In M74, there is a 5' upstream sequence of 141 nucleotides (nt), which contains regulatory signals for internal translation of the preprotoxin open reading frame (ORF) at the second AUG codon. The first AUG close to the 5' end is not functional. For K74 analysis, M74 viruses were first introduced into laboratory strains of Saccharomyces cerevisiae. We show here that the mature toxin is an α/β heterodimer linked by disulfide bonds. Though the toxin (or preprotoxin) confers immunity to the carrier, cells with increased K74 loads have a sick phenotype that may lead to cell death. Thus, a fine-tuning of K74 production by the upstream regulatory sequence is essential for the host cell to benefit from the toxin it produces and, at the same time, to safely avoid damage by an excess of toxin. IMPORTANCE Killer yeasts produce toxins to which they are immune by mechanisms not well understood. This self-immunity, however, is compromised in certain strains, which secrete an excess of toxin, leading to sick cells or suicidal phenotypes. Thus, a fine-tuning of toxin production has to be achieved to reach a balance between the beneficial effect of toxin production and the stress imposed on the host metabolism. K74 toxin from S. paradoxus is very active against Saccharomyces uvarum, among other yeasts, but an excess of toxin production is deleterious for the host. Here, we report that the presence of a 5' 141-nt upstream sequence downregulates K74 toxin precursor translation, decreasing toxin levels 3- to 5-fold. Thus, this is a special case of translation regulation performed by sequences on the M74 genome itself, which have been presumably incorporated into the viral RNA during evolution for that purpose.

A gene drive does not spread easily in populations of the honey bee parasite Varroa destructor

Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from varroa. More importantly, in some populations varroa mites have developed resistance to available acaricides. Overcoming the varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control varroa. We show that spreading a neutral gene drive in varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles.

Fructooligosaccharide decreases the production of uremic toxin precursor through modulating gut microbes mediated tyrosine metabolism pathway

Fructooligosaccharide (FOS) is one of the most important and well-known prebiotics that confers health benefits on the host. The effect of FOS is frequently associated with modulation of the abundance of gut microbes. However, the effect of FOS on gut microbes-mediated metabolism pathway remains largely undefined. This study aimed to explore the modulation effect of FOS on the metabolism pathway of tyrosine in gut microbes. Moreover, the effect of FOS on the production of p-cresol by gut microbes was studied, in which p-cresol is a uremic toxin precursor produced by tyrosine metabolism pathway. The results showed that FOS significantly prompted the anabolism pathway of tyrosine, which might promote the proliferation of gut microbes. Additionally, FOS significantly inhibited the catabolism pathway of tyrosine, therefore decreased p-cresol production in tyrosine oxidative catabolism pathway. Two mechanisms were proposed to explain the effect of FOS, one was to switch tyrosine catabolism from oxidative pathway to reductive pathway, the other was to directly inhibit the oxidative pathway in which p-cresol was produced. In conclusion, the present study suggested that as a well-known prebiotic, FOS inhibited the biosynthesis of p-cresol in gut microbes by regulating gut microbes-mediated tyrosine metabolism.

Disentangling the abiotic and biotic components of AMF suppressive soils

Arbuscular mycorrhizal fungi (AMF) are important in plant nutrient uptake, but their function is prone to environmental constraints including soil factors that may suppress AMF transfer of phosphorus (P) from the soil to the plant. The objective of this study was to disentangle the biotic and abiotic components of AMF-suppressive soils. Suppression was measured in terms of AMF-mediated plant uptake of 33P mixed into a patch of soil and treatments included soil sterilization, soil mixing, pH manipulation and inoculation with isolated soil fungi. The degree of suppression was compared to volatile organic compound (VOC) production by isolated fungi and to multi-element analysis of soils. For a selected suppressive soil, sterilization and soil mixing experiments confirmed a biotic component of suppression. A Fusarium isolate from that soil suppressed the AMF activity and produced greater amounts than other fungal isolates of the antimicrobial VOC trichodiene (a trichothecene toxin precursor), beta-chamigrene, alpha-cuprenene and p-xylene. These metabolites deserve further attention when unravelling the chemical background behind the suppression of AMF activity by soil microorganisms. For the abiotic component of suppression, soil liming and acidification experiments confirmed that suppression was strongest at low pH. The pH effect might be associated with changed availability of specific suppressive elements. Indeed 33P uptake from the soil patches correlated negatively to Al levels and Al toxicity seems to play a major role in the AMF suppressiveness at pH below 5.0–5.2. However, the documentation of a biotic component of suppression for both low and high pH soils leads to the conclusion that biotic and abiotic components of suppression may act in parallel in some soils. The current insight into the components of soil suppressiveness of the AMF activity aids to develop management practices that allow for optimization of AMF functionality.

Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients.

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Adsorption of Phenazines Produced by Pseudomonas aeruginosa Using AST-120 Decreases Pyocyanin-Associated Cytotoxicity.

AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection.

Chronic Kidney Disease, Gut Dysbiosis, and Constipation: A Burdensome Triplet.

Gut dysbiosis has been implicated in the progression of chronic kidney disease (CKD). Alterations in the gut environment induced by uremic toxins, the dietary restriction of fiber-rich foods, and multiple drugs may be involved in CKD-related gut dysbiosis. CKD-related gut dysbiosis is considered to be characterized by the expansion of bacterial species producing precursors of harmful uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, and the contraction of species generating beneficial short-chain fatty acids, such as butyrate. Gut-derived uremic toxins cause oxidative stress and pro-inflammatory responses, whereas butyrate exerts anti-inflammatory effects and contributes to gut epithelial integrity. Gut dysbiosis is associated with the disruption of the gut epithelial barrier, which leads to the translocation of endotoxins. Research on CKD-related gut dysbiosis has mainly focused on chronic inflammation and consequent cardiovascular and renal damage. The pathogenic relationship between CKD-related gut dysbiosis and constipation has not yet been investigated in detail. Constipation is highly prevalent in CKD and affects the quality of life of these patients. Under the pathophysiological state of gut dysbiosis, altered bacterial fermentation products may play a prominent role in intestinal dysmotility. In this review, we outline the factors contributing to constipation, such as the gut microbiota and bacterial fermentation; introduce recent findings on the pathogenic link between CKD-related gut dysbiosis and constipation; and discuss potential interventions. This pathogenic link needs to be elucidated in more detail and may contribute to the development of novel treatment options not only for constipation, but also cardiovascular disease in CKD.

In vitro activity of AST-120 that suppresses indole signaling in Escherichia coli, which attenuates drug tolerance and virulence.

AST-120 (Kremezin) is used to treat progressive chronic kidney disease (CKD) by adsorbing uremic toxin precursors produced by gut microbiota, such as indole and phenols. In this study, we propose that AST-120 reduces indole level, consequently suppresses indole effects on induction of drug tolerance and virulence in Escherichia coli including enterohaemorrhagic strains. In experiments, AST-120 adsorbed both indole and tryptophan, a precursor of indole production, and led to decreased expression of acrD and mdtEF which encode drug efflux pumps, and elevated glpT, which encodes a transporter for fosfomycin uptake and increases susceptibility to aztreonam, rhodamine 6G, and fosfomycin. AST-120 also decreased the production of EspB, which contributes to pathogenicity of enterohaemorrhagic E. coli (EHEC). Aztreonam, ciprofloxacin, minocycline, trimethoprim, and sulfamethoxazole were also adsorbed by AST-120. However, fosfomycin, in addition to rifampicin, colistin and amikacin were not adsorbed, thus AST-120 can be used together with these drugs for therapy to treat infections. These results suggest another benefit of AST-120, i.e., that it assists antibacterial chemotherapy.