FHOD-1 is the only formin in Caenorhabditis elegans that promotes striated muscle growth and Z-line organization in a cell autonomous manner.

The striated body wall muscles of Caenorhabditis elegans are a simple model for sarcomere assembly. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, develop thin muscles with abnormal dense bodies (the sarcomere Z-line analogs). However, this work left in question whether these formins work in a muscle cell autonomous manner, particularly since cyk-1(∆) deletion has pleiotropic effects on development. Using a fast acting temperature-sensitive cyk-1(ts) mutant, we show here that neither postembryonic loss nor acute loss of CYK-1 during embryonic sarcomerogenesis cause lasting muscle defects. Furthermore, mosaic expression of CYK-1 in cyk-1(∆) mutants is unable to rescue muscle defects in a cell autonomous manner, suggesting muscle phenotypes caused by cyk-1(∆) are likely indirect. Conversely, mosaic expression of FHOD-1 in fhod-1(Δ) mutants promotes muscle cell growth and proper dense body organization in a muscle cell autonomous manner. As we observe no effect of loss of any other formin on muscle development, we conclude FHOD-1 is the only worm formin that directly promotes striated muscle development, and the effects on formin loss in C. elegans are surprisingly modest compared to other systems.

CATP-8/P5A ATPase Regulates ER Processing of the DMA-1 Receptor for Dendritic Branching.

Dendrite morphogenesis is essential for a neuron to establish its receptive field and is, thus, the anatomical basis for the proper functioning of the nervous system. The molecular mechanisms governing dendrite branching are not fully understood. Using the multi-dendritic PVD neuron in the nematode Caenorhabditis elegans, we identify CATP-8/P5A ATPase as a key regulator of dendrite branching that controls the translocation of the DMA-1 receptor to the endoplasmic reticulum (ER). The specific signal peptide of DMA-1 and the ATPase activity of CATP-8 are essential for this process. Our results reveal that P5A ATPase may regulate protein translocation in the ER.

Silver(i) complexes with different pyridine-4,5-dicarboxylate ligands as efficient agents for the control of cow mastitis associated pathogens.

Infections of the cow udder leading to mastitis and lower milk quality are one of the biggest problems in the dairy industry worldwide. Unfortunately, therapeutic options for the treatment of cow mastitis are limited as a consequence of the development of pathogens that are resistant to conventionally used antibiotics. In the search for agents that will be active against cow mastitis associated pathogens, in the present study, five new silver(i) complexes with different chelating pyridine-4,5-dicarboxylate types of ligands, [Ag(NO3)(py-2py)]n (1), [Ag(NO3)(py-2metz)]n (2), [Ag(CH3CN)(py-2py)]BF4 (3), [Ag(py-2tz)2]BF4 (4) and [Ag(py-2metz)2]BF4 (5), py-2py is dimethyl 2,2'-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis. These complexes showed remarkable activity against the standard panel of microorganisms and a selection of clinical isolates from the milk of the cow diagnosed with mastitis. With the aim of determining the therapeutic potential of silver(i) complexes, their toxicity in vivo against the model organism, Caenorhabditis elegans (C. elegans), was investigated. The complexes that had the best therapeutic profile, 2 and 5, induced bacterial membrane depolarization and the production of reactive oxygen species (ROS) in Candida albicans cells and inhibited the hyphae as well as the biofilm formation. Taken together, the presented data suggest that the silver(i) complexes with pyridine ligands could be considered for the treatment of microbial pathogens, which are causative agents of cow mastitis.

Fine Particulate Matter Leads to Unfolded Protein Response and Shortened Lifespan by Inducing Oxidative Stress in C. elegans.

Oxidative stress has been proven as one of the most critical regulatory mechanisms involved in fine Particulate Matter- (PM2.5-) mediated toxicity. For a better understanding of the underlying mechanisms that enable oxidative stress to participate in PM2.5-induced toxic effects, the current study explored the effects of oxidative stress induced by PM2.5 on UPR and lifespan in C. elegans. The results implicated that PM2.5 exposure induced oxidative stress response, enhanced metabolic enzyme activity, activated UPR, and shortened the lifespan of C. elegans. Antioxidant N-acetylcysteine (NAC) could suppress the UPR through reducing the oxidative stress; both the antioxidant NAC and UPR inhibitor 4-phenylbutyric acid (4-PBA) could rescue the lifespan attenuation caused by PM2.5, indicating that the antioxidant and moderate proteostasis contribute to the homeostasis and adaptation to oxidative stress induced by PM2.5.

Isolation of a Novel Flavanonol and an Alkylresorcinol with Highly Potent Anti-Trypanosomal Activity from Libyan propolis.

Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4'-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.

Antagonistic paralogs control a switch between growth and pathogen resistance in C. elegans.

Immune genes are under intense, pathogen-induced pressure, which causes these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described a C. elegans-specific gene called pals-22 to be a repressor of "Intracellular Pathogen Response" or IPR genes. Here we describe pals-25, which, like pals-22, is a species-specific gene of unknown biochemical function. We identified pals-25 in a screen for suppression of pals-22 mutant phenotypes and found that mutations in pals-25 suppress all known phenotypes caused by mutations in pals-22. These phenotypes include increased IPR gene expression, thermotolerance, and immunity against natural pathogens, including Nematocida parisii microsporidia and the Orsay virus. Mutations in pals-25 also reverse the reduced lifespan and slowed growth of pals-22 mutants. Transcriptome analysis indicates that pals-22 and pals-25 control expression of genes induced not only by natural pathogens of the intestine, but also by natural pathogens of the epidermis. Indeed, in an independent forward genetic screen we identified pals-22 as a repressor and pals-25 as an activator of epidermal defense gene expression. In summary, the species-specific pals-22 and pals-25 genes act as a switch to regulate a program of gene expression, growth, and defense against diverse natural pathogens in C. elegans.

Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi.

Ostertagia ostertagi (OO) is a widespread parasite that causes chronic infection in cattle and leads to annual losses of billions of dollars in the cattle industry. It remains unclear why cattle are unable to mount an effective immune response despite a large influx of immune cells to the infected abomasal mucosa and draining lymph nodes. Neutrophils, the immune system's first responders, have the capacity to release neutrophil extracellular traps (NETs) to contain various pathogens, including some parasites. In the present study, the mechanisms by which O. ostertagi influences bovine NET formation were investigated. O. ostertagi larval soluble extract (OO extract) was able to induce typical NETs by purified neutrophils in vitro, confirmed by co-localization of extracellular DNA with typical NET-associated proteins histone and neutrophil elastase (NE). Consistent with existing literature, inhibition assays demonstrated that these OO extract-induced NETs were dependent upon the enzymes NADPH oxidase and myeloperoxidase (MPO). Live OO stage 4 larvae (L4) stimulated neutrophils to form NETs similar to those induced by OO extract. Bovine neutrophils also released NETs in response to Caenorhabditis elegans, a free-living soil nematode, suggesting that bovine NET production may be a conserved mechanism against a broad range of nematodes. This is the first report demonstrating O. ostertagi-induced NET formation by bovine neutrophils, a potentially underappreciated mechanism in the early immune response against nematode infections.

A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans.

Caenorhabditis elegans is a useful organism for testing chemical effects on physiology. Whole organism small molecule screens offer significant advantages for identifying biologically active chemical structures that can modify complex phenotypes such as lifespan. Described here is a simple protocol for producing hundreds of 96-well culture plates with fairly consistent numbers of C. elegans in each well. Next, we specified how to use these cultures to screen thousands of chemicals for effects on the lifespan of the nematode C. elegans. This protocol makes use of temperature sensitive sterile strains, agar plate conditions, and simple animal handling to facilitate the rapid and high throughput production of synchronized animal cultures for screening.

[Determination of the role of Salmonella enterica plasmids in antibiotic susceptibility and Caenorhabditis elegans pathogenicity]. / Salmonella enterica plazmitlerinin antibiyotik duyarliligi ve Caenorhabditis elegans patojenitesindeki rollerinin belirlenmesi.

Poultry animals and poultry associated products are important risk sources for Salmonellosis. S.Kentucky and S.Infantis are among the serovars frequently isolated from retail chickens and were reported to be isolated in Turkey. In this study, the role of plasmids carried by S.Kentucky and S.Infantis isolates in antibiotic resistance profiles of the isolates and their pathogenicity on Caenorhabditis elegans nematode model system were investigated. The isolates used, 1 of Kentucky and 2 of Infantis serotypes, were selected among food-borne Salmonella isolated from chicken carcass in Edirne. All three isolates were previously shown to contain plasmids carrying multidrug resistance and were known to be pathogenic on C.elegans nematode model system. S.Kentucky A10 isolate was resistant to ampicillin, nalidixic acid, tetracycline, ciprofloxacin, trimethoprim and sulphonamide and carried one plasmid with 31.6 kb size. S.Infantis A15 isolate was resistant to ampicillin, streptomycine, nalidixic acid, tetracycline, neomycin, sulphonamide and kanamycin and carried a plasmid with 19.9 kb size while the other S.Infantis isolate (A16) was resistant to streptomycin, nalidixic acid, tetracycline, trimethoprim, neomycin, sulphonamide and kanamycin and carried 3 plasmids with 42.4, 1.5 and 1.2 kb sizes. Plasmid curing experiments were performed to investigate the role of plasmids in antibiotic resistance and pathogenicity in C.elegans. Ethidium bromide (EtBr) dye was used as the plasmid curing agent. Plasmids were isolated from cultures grown in LB broth with different concentrations of EtBr (50, 75, 100, 125 µg/ml) according to the Kado-Liu method and the most effective EtBr concentration was determined as 125 µg/ml. C.elegans pathogenicity assays were carried out using plasmid cured isolates. The time 50% of the nematode die (TD50) values of the nematode groups fed with plasmid cured isolates were compared with previously obtained TD50 values of the nematode groups fed with wild type Salmonella isolates. Studentðs t-test (p< 0.05) was used to showthe level of significance between TD50 values of the two groups. TD50 values of the positive control group fed with S.Typhimurium ATCC 14028 and the negative control group fed with Escherichia coli OP50 were found as 4.0 ± 0.4 and 8.0 ± 0.02 days, respectively. The differences between TD50 values of nematode groups fed with wild type and plasmid cured isolates were statistically significant both for S.Kentucky (A10) (4.9 ± 0.04-6.2 ± 0.1) and S.Infantis (A16) (4.4 ± 0.01-6.2 ± 0.2) (p< 0.05) strains, but no significant difference was observed for the groups fed with wild type and plasmid cured S.Infantis (A15) (5.7 ± 0.39-5.8 ± 0.16) strain. Broth microdilution method was used to determine whether there was any change in minimal inhibitory concentrations (MIC) of the antibiotics for which the isolates were resistant before plasmid elimination. No significant difference was found between the MIC values of the resistant antibiotics among Salmonella isolates carrying plasmids and with cured plasmid. This study is important since the first in vivo results about the role of Kentucky and Infantis serovar plasmids on C.elegans nematode model system were presented.

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants.

Bisphenols, such as bisphenol A (BPA) and bisphenol S (BPS) are polymerizing agents widely used in the production of plastics and numerous everyday-use products. Based on their chemical structure and estradiol-like biological properties, they have been classified as endocrine disrupting compounds (EDC). Long-term exposure to EDCs, even at low doses, has been linked to various health defects including cancer, behavioral disorders and infertility, with greater vulnerability indicated during early developmental periods. Cellular and molecular studies with the genetically tractable nematode model Caenorhabditis elegans have demonstrated that exposure to BPA causes apoptosis, embryonic lethality and disruption in the DNA repair mechanisms. We have previously reported that exposure of C. elegans embryos to low doses of different bisphenols decreases fecundity. In addition, we have shown that the effects of exposure during the very early stages of development persist into adulthood as assayed by quantifying habituation behavior, a form of non-associative learning. Here, we provide detailed protocols for embryonic exposure to low-dose EDCs as well as the associated fecundity and anterior touch habituation assays, along with representative results.

Using a Microfluidics Device for Mechanical Stimulation and High Resolution Imaging of C. elegans.

One central goal of mechanobiology is to understand the reciprocal effect of mechanical stress on proteins and cells. Despite its importance, the influence of mechanical stress on cellular function is still poorly understood. In part, this knowledge gap exists because few tools enable simultaneous deformation of tissue and cells, imaging of cellular activity in live animals, and efficient restriction of motility in otherwise highly mobile model organisms, such as the nematode Caenorhabditis elegans. The small size of C. elegans makes them an excellent match to microfluidics-based research devices, and solutions for immobilization have been presented using microfluidic devices. Although these devices allow for high-resolution imaging, the animal is fully encased in polydimethylsiloxane (PDMS) and glass, limiting physical access for delivery of mechanical force or electrophysiological recordings. Recently, we created a device that integrates pneumatic actuators with a trapping design that is compatible with high-resolution fluorescence microscopy. The actuation channel is separated from the worm-trapping channel by a thin PDMS diaphragm. This diaphragm is deflected into the side of a worm by applying pressure from an external source. The device can target individual mechanosensitive neurons. The activation of these neurons is imaged at high-resolution with genetically-encoded calcium indicators. This article presents the general method using C. elegans strains expressing calcium-sensitive activity indicator (GCaMP6s) in their touch receptor neurons (TRNs). The method, however, is not limited to TRNs nor to calcium sensors as a probe, but can be expanded to other mechanically-sensitive cells or sensors.

Studies on reproductive stress caused by candidate Gram positive and Gram negative bacteria using model organism, Caenorhabditis elegans.

Microbial association with a host using model system C. elegans have been widely studied based on factors such as host survival, the mode of infection, disease pathogenesis and the role of various players regulated during infection. The influence of pathogenic microorganism on reproduction and associated issues has not been explored fully. The present study focuses on the impact of bacterial infection on male reproductive parameters such as spermatogenesis and spermiogenesis, including physiological aspects like tail morphology defect and underlying molecular mechanisms that have been perturbed. In order to compare the consequence of infection caused by Gram positive and negative bacteria, Staphylococcus aureus and Vibrio alginolyticus were chosen as candidate pathogens, respectively. Microscopic observations revealed notable changes in tail morphology during 24 h of infection, as along with change in sperm size and activation. The Real Time-PCR results suggest the plausible down regulation of DBL-1/TGF-ß pathway suggesting the morphological change in the tail. Shotgun proteomics further lead to the identification of MAG-1, Magonashi Protein a candidate regulatory player that affects spermatogenesis and HIF-1 that regulate during stress in both Gram positive and Gram negative infection. The protein-protein interaction with detected proteins revealed RACK-1 protein and mTOR pathway in S. aureus and V. alginolyticus respectively interacting with MAG-1 protein, which plays an important role in spermatogenesis termination in hermaphrodites during L4 to adult switch. This study paves a way to understand the candidate players that regulate reproduction during bacterial infection.

5-hydroxymethyl-2-furaldehyde from marine bacterium Bacillus subtilis inhibits biofilm and virulence of Candida albicans.

Candida albicans is considered as the primary etiologic agent of candidiasis, a very common fungal infection in human. The yeast to hyphal transition and ability to form hypoxic biofilm on medical devices is well allied with virulence and antifungal resistance of C. albicans. Antagonistic agents that inhibit biofilm formation and alter susceptibility of C. albicans to conventional antifungals is of profound need. The present study explores the antibiofilm efficacy of Bacillus subtilis, a marine bacterial isolate from Palk Bay against C. albicans. Mass spectrometric analysis of ethyl acetate extract of B. subtilis unveiled 5-hydroxymethyl-2-furaldehyde (5HM2F) as one of its major components. 5HM2F demonstrated concentration dependent biofilm inhibition, which was also corroborated through microscopic analysis. Furthermore, 5HM2F was effective in inhibiting other virulence factors of C. albicans such as morphological transition and secreted hydrolases production. Fourier transform infrared spectroscopic analysis showed alteration in amide bond region. The reduction in ergosterol content and increased antifungal susceptibility was well allied with real time PCR result, which showed down regulation of genes involved in drug resistance mechanisms. In vivo study using Caenorhabditis elegans also substantiated the antivirulence efficacy of 5HM2F at in vivo condition. Thus, the present study reports the therapeutic potential of 5HM2F against C. albicans infections.

Tailored environments to study motile cells and pathogens.

Motile cells and pathogens migrate in complex environments and yet are mostly studied on simple 2D substrates. In order to mimic the diverse environments of motile cells, a set of assays including substrates of defined elasticity, microfluidics, micropatterns, organotypic cultures, and 3D gels have been developed. We briefly introduce these and then focus on the use of micropatterned pillar arrays, which help to bridge the gap between 2D and 3D. These structures are made from polydimethylsiloxane, a moldable plastic, and their use has revealed new insights into mechanoperception in Caenorhabditis elegans, gliding motility of Plasmodium, swimming of trypanosomes, and nuclear stability in cancer cells. These studies contributed to our understanding of how the environment influences the respective cell and inform on how the cells adapt to their natural surroundings on a cellular and molecular level.

Caenorhabditis elegans models of tauopathy.

One of the hallmarks of the tauopathies, which include the neurodegenerative disorders, such as Alzheimer disease (AD), corticobasal degeneration, frontotemporal dementia, and progressive supranuclear palsy (PSP), is the abnormal accumulation of post-translationally modified, insoluble tau. The result is a loss of neurons, decreased mental function, and complete dependence of patients on others. Aggregation of tau, which under physiologic conditions is a highly soluble protein, is thought to be central to the pathogenesis of these diseases. Indeed one of the strongest lines of evidence is the MAPT gene polymorphisms that lead to the familial forms of tauopathy. Extensive research in animal models over the years has contributed some of the most important findings regarding the pathogenesis of these diseases. Despite this, the precise molecular mechanisms that lead to abnormal tau folding, accumulation, and spreading remain unknown. Owing to the fact that most of the biochemical pathways are conserved, Caenorhabditis elegans provides an alternative approach to identify cellular mechanisms and druggable genes that operate in such disorders. Many human genes implicated in neurodegenerative diseases have counterparts in C. elegans, making it an excellent model in which to study their pathogenesis. In this article, we review some of the important findings gained from C. elegans tauopathy models.-Pir, G. J., Choudhary, B., Mandelkow, E. Caenorhabditiselegans models of tauopathy.

High-resolution imaging of muscle attachment structures in Caenorhabditis elegans.

We used structured illumination microscopy (SIM) to obtain super-resolution images of muscle attachment structures in Caenorhabditis elegans striated muscle. SIM imaging of M-line components revealed two patterns: PAT-3 (ß-integrin) and proteins that interact in a complex with the cytoplasmic tail of ß-integrin and localize to the basal muscle cell membrane [UNC-112 (kindlin), PAT-4 (ILK), UNC-97 (PINCH), PAT-6 (α-parvin), and UNC-95], are found in discrete, angled segments with gaps. In contrast, proteins localized throughout the depth of the M-line (UNC-89 (obscurin) and UNC-98) are imaged as continuous lines. Systematic immunostaining of muscle cell boundaries revealed that dense body components close to the basal muscle cell membrane also localize at cell boundaries. SIM imaging of muscle cell boundaries reveal "zipper-like" structures. Electron micrographs reveal electron dense material similar in appearance to dense bodies located adjacent to the basolateral cell membranes of adjacent muscle cells separated by ECM. Moreover, by EM, there are a variety of features of the muscle cell boundaries that help explain the zipper-like pattern of muscle protein localization observed by SIM. Short dense bodies in atn-1 mutants that are null for α-actinin and lack the deeper extensions of dense bodies, showed "zipper-like" structures by SIM similar to cell boundary structures, further indicating that the surface-proximal components of dense bodies form the "zipper-like" structures at cell boundaries. Moreover, mutants in thin and thick filament components do not have "dot-like" dense bodies, suggesting that myofilament tension is required for assembly or maintenance of proper dense body shape.

Dimerization of the fungal defense lectin CCL2 is essential for its toxicity against nematodes.

Lectins are used as defense effector proteins against predators, parasites and pathogens by animal, plant and fungal innate defense systems. These proteins bind to specific glycoepitopes on the cell surfaces and thereby interfere with the proper cellular functions of the various antagonists. The exact cellular toxicity mechanism is in many cases unclear. Lectin CCL2 of the mushroom Coprinopsis cinerea was previously shown to be toxic for Caenorhabditis elegans and Drosophila melanogaster. This toxicity is dependent on a single, high-affinity binding site for the trisaccharide GlcNAc(Fucα1,3)ß1,4GlcNAc, which is a hallmark of nematode and insect N-glycan cores. The carbohydrate-binding site is located at an unusual position on the protein surface when compared to other ß-trefoil lectins. Here, we show that CCL2 forms a compact dimer in solution and in crystals. Substitution of two amino acid residues at the dimer interface, R18A and F133A, interfered with dimerization of CCL2 and reduced toxicity but left carbohydrate-binding unaffected. These results, together with the positioning of the two carbohydrate-binding sites on the surface of the protein dimer, suggest that crosslinking of N-glycoproteins on the surface of intestinal cells of invertebrates is a crucial step in the mechanism of CCL2-mediated toxicity. Comparisons of the number and positioning of carbohydrate-binding sites among different dimerizing fungal ß-trefoil lectins revealed a considerable variability in the carbohydrate-binding patterns of these proteins, which are likely to correlate with their respective functions.

Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus.

Fatty acid and retinol-binding proteins (FARs) comprise a family of unusual α-helix rich lipid-binding proteins found exclusively in nematodes. They are secreted into host tissues by parasites of plants, animals and humans. The structure of a FAR protein from the free-living nematode Caenorhabditis elegans is available, but this protein [C. elegans FAR-7 (Ce-FAR-7)] is from a subfamily of FARs that does not appear to be important at the host/parasite interface. We have therefore examined [Necator americanus FAR-1 (Na-FAR-1)] from the blood-feeding intestinal parasite of humans, N. americanus. The 3D structure of Na-FAR-1 in its ligand-free and ligand-bound forms, determined by NMR (nuclear magnetic resonance) spectroscopy and X-ray crystallography respectively, reveals an α-helical fold similar to Ce-FAR-7, but Na-FAR-1 possesses a larger and more complex internal ligand-binding cavity and an additional C-terminal α-helix. Titration of apo-Na-FAR-1 with oleic acid, analysed by NMR chemical shift perturbation, reveals that at least four distinct protein-ligand complexes can be formed. Na-FAR-1 and possibly other FARs may have a wider repertoire for hydrophobic ligand binding, as confirmed in the present study by our finding that a range of neutral and polar lipids co-purify with the bacterially expressed recombinant protein. Finally, we show by immunohistochemistry that Na-FAR-1 is present in adult worms with a tissue distribution indicative of possible roles in nutrient acquisition by the parasite and in reproduction in the male.

Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance.

Bacterial communication plays an important role in many population-based phenotypes and interspecies interactions, including those in host environments. These interspecies interactions may prove critical to some infectious diseases, and it follows that communication between pathogenic bacteria and commensal bacteria is a subject of growing interest. Recent studies have shown that Escherichia coli uses the signaling molecule indole to increase antibiotic tolerance throughout its population. Here, we show that the intestinal pathogen Salmonella typhimurium increases its antibiotic tolerance in response to indole, even though S. typhimurium does not natively produce indole. Increased antibiotic tolerance can be induced in S. typhimurium by both exogenous indole added to clonal S. typhimurium populations and indole produced by E. coli in mixed-microbial communities. Our data show that indole-induced tolerance in S. typhimurium is mediated primarily by the oxidative stress response and, to a lesser extent, by the phage shock response, which were previously shown to mediate indole-induced tolerance in E. coli. Further, we find that indole signaling by E. coli induces S. typhimurium antibiotic tolerance in a Caenorhabditis elegans model for gastrointestinal infection. These results suggest that the intestinal pathogen S. typhimurium can intercept indole signaling from the commensal bacterium E. coli to enhance its antibiotic tolerance in the host intestine.