scholarly journals An intestinally secreted host factor limits bacterial colonization but promotes microsporidia invasion of C. elegans

2021 ◽  
Author(s):  
Hala Tamim El Jarkass ◽  
Calvin Mok ◽  
Michael R Schertzberg ◽  
Andrew G Fraser ◽  
Emily R Troemel ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Bacterial Pathogen ◽  
Oral Route ◽  
Intestinal Lumen ◽  
Parasite Invasion ◽  
Competitive Fitness ◽  
Obligate Intracellular ◽  
C Elegans ◽  
Fitness Advantage ◽  
Trade Offs

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression of AAIM-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favoured in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild type animals. Together, this work demonstrates how microsporidia exploits an antibacterial immune protein to promote host invasion. Our results also highlight the evolutionary trade-offs that exist to optimizing host defense against multiple classes of pathogens.

scholarly journals An intestinally secreted host factor promotes microsporidia invasion of C. elegans

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Hala Tamim El Jarkass ◽  
Calvin Mok ◽  
Michael R Schertzberg ◽  
Andrew G Fraser ◽  
Emily R Troemel ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Oral Route ◽  
Intestinal Lumen ◽  
Wild Type ◽  
Parasite Invasion ◽  
Competitive Fitness ◽  
Obligate Intracellular ◽  
C Elegans ◽  
Fitness Advantage ◽  
Trade Offs

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression of AAIM-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favoured in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild type animals. Together, this work demonstrates how microsporidia exploits a secreted protein to promote host invasion. Our results also suggest evolutionary trade-offs may exist to optimizing host defense against multiple classes of pathogens.

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

2010 ◽  
Vol 3 (3) ◽  
pp. 1057-1064 ◽  
Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S
Keyword(s):  
Diabetes Mellitus ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Oral Route ◽  
The Body ◽  
Current Status ◽  
Intestinal Lumen ◽  
Insulin Administration ◽  
Novel Approaches ◽  
Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

scholarly journals Interactions between the Prophage 919TP and Its Vibrio cholerae Host: Implications of gmd Mutation for Phage Resistance, Cell Auto-Aggregation, and Motility

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2342
Author(s):  
Na Li ◽  
Yigang Zeng ◽  
Bijie Hu ◽  
Tongyu Zhu ◽  
Sine Lo Svenningsen ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Genomic Analysis ◽  
Resistant Mutant ◽  
Resistance Mechanisms ◽  
Phage Resistance ◽  
Comparative Genomic ◽  
Lytic Phage ◽  
O Antigen ◽  
Trade Offs ◽  
Base Pair Deletion

Prophage 919TP is widely distributed among Vibrio cholera and is induced to produce free φ919TP phage particles. However, the interactions between prophage φ919TP, the induced phage particle, and its host remain unknown. In particular, phage resistance mechanisms and potential fitness trade-offs, resulting from phage resistance, are unresolved. In this study, we examined a prophage 919TP-deleted variant of V. cholerae and its interaction with a modified lytic variant of the induced prophage (φ919TP cI-). Specifically, the phage-resistant mutant was isolated by challenging a prophage-deleted variant with lytic phage φ919TP cI-. Further, the comparative genomic analysis of wild-type and φ919TP cI--resistant mutant predicted that phage φ919TP cI- selects for phage-resistant mutants harboring a mutation in key steps of lipopolysaccharide (LPS) O-antigen biosynthesis, causing a single-base-pair deletion in gene gmd. Our study showed that the gmd-mediated O-antigen defect can cause pleiotropic phenotypes, e.g., cell autoaggregation and reduced swarming motility, emphasizing the role of phage-driven diversification in V. cholerae. The developed approach assists in the identification of genetic determinants of host specificity and is used to explore the molecular mechanism underlying phage-host interactions. Our findings contribute to the understanding of prophage-facilitated horizontal gene transfer and emphasize the potential for developing new strategies to optimize the use of phages in bacterial pathogen control.

scholarly journals Avoidance of Contaminated Food Correlates With Low Protozoan Infection in Bonobos

2021 ◽  
Vol 9 ◽  
Author(s):  
Cécile Sarabian ◽  
Raphaël Belais ◽  
Andrew J. J. MacIntosh
Keyword(s):  
Infectious Agent ◽  
Oral Route ◽  
Behavioral Experiments ◽  
Food Items ◽  
Individual Fitness ◽  
Behavioral Adaptations ◽  
Trade Offs ◽  
Protozoan Infection ◽  
Contaminated Food ◽  
The Individual

Intense selection pressure from parasites on free-living animals has resulted in behavioral adaptations that help potential hosts avoid sources of infection. In primates, such “behavioral immunity” is expressed in different contexts and may vary according to the ecology of the host, the nature of the infectious agent, and the individual itself. In this study, we investigated whether avoidance of contaminated food was associated with reduced parasite infection in sanctuary-housed bonobos. To do this, we used bonobos’ responses to soil- and fecally-contaminated food in behavioral experiments, and then compared the results with an estimate of protozoan infection across individuals. We found that avoidance of contaminated food correlated negatively with Balantioides coli infection, a potentially pathogenic protozoan transmitted through the fecal-oral route. The association between avoidance responses and parasitism were most evident in experiments in which subjects were offered a choice of food items falling along a gradient of fecal contamination. In the case of experiments with more limited options and a high degree of contamination, most subjects were averse to the presented food item and this may have mitigated any relationship between feeding decisions and infection. In experiments with low perceived levels of contamination, most subjects consumed previously contaminated food items, which may also have obscured such a relationship. The behavioral immunity observed may be a consequence of the direct effects of parasites (infection), reflecting the first scale of a landscape of disgust: individual responses. Indirect effects of parasites, such as modulation of feeding decisions and reduced social interactions—and their potential trade-offs with physiological immunity—are also discussed in light of individual fitness and primate evolution. This study builds on previous work by showing that avoidance behaviors may be effective in limiting exposure to a wide diversity of oro-fecally transmitted parasites.

scholarly journals Selection and niche trade-offs in biofilm-forming bacterial communities in experimental microcosms

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Robyn Jerdan ◽  
Scott Cameron ◽  
Emily Donaldson ◽  
Andrew Spiers
Keyword(s):  
Biofilm Formation ◽  
Liquid Column ◽  
Significant Shift ◽  
Bet Hedging ◽  
Transfer Experiment ◽  
Serial Transfer ◽  
Fitness Advantage ◽  
Trade Offs ◽  
Selection For ◽  
Cell Densities

Static microcosms are a well-established system used to study the adaptive radiation of Pseudomonas fluorescens SBW25 and the adaptive biofilm-forming mutants known as the Wrinkly Spreaders (WS). We have developed this system to investigate selection within multi-species communities using a soil-wash inoculum dominated by biofilm-competent pseudomonads. Here we present community and isolate-level analyses of one serial-transfer experiment in which replicate populations were selected for over ten transfers and 60 days. Although no significant trends in improving community biofilm characteristics or total microcosm productivity were observed, a significant shift in biofilm-formation and microcosm growth by individual isolates recovered from the initial soil-wash inoculum and final transfers indicated that these communities were subject to selection for growth in these microcosms. Surprisingly, the fitness of the archetypal WS was poor when competing against community samples, and having compared the cell densities in the low-O2 region of liquid column below the biofilm, we suggest that part of the community’s fitness advantage comes from the ability to colonise this under-utilised niche as well as to compete at the A-L interface. Samples from the community biofilms and the low-O2 region were able to re-colonize both niches and many final transfer isolates grew throughout the liquid column as well as forming A-L interface biofilms. This suggests that there is a trade-off between fast growth under highly competitive conditions at the A-L interface and slower growth with less competition in the low-O2 region, with some isolates taking a bet-hedging approach a colonizing both niches in our microcosm system.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2020 ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Mortality Risk ◽  
Future Generations ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
C Elegans ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

AbstractDietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

scholarly journals Fitness Trade-Offs in blaTEM Evolution

2008 ◽  
Vol 52 (7) ◽  
pp. 2340-2345 ◽  
Author(s):  
Joanna E. Mroczkowska ◽  
Miriam Barlow
Keyword(s):  
Microbial Populations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Bacterial Populations ◽  
Real Time Quantitative Pcr ◽  
Fitness Effects ◽  
Fitness Advantage ◽  
Extended Spectrum ◽  
Trade Offs ◽  
Pcr Method

ABSTRACT bla TEM-1 expression results in penicillin resistance, whereas expression of many bla TEM-1 descendants, called extended-spectrum β-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla TEM-1 is still the most abundant bla TEM allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla TEM-1 descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla TEM-1, bla TEM-10, and bla TEM-12. Our results show that bacteria expressing the ancestral bla TEM-1 allele have a fitness advantage over those expressing either bla TEM-10 or bla TEM-12 when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla TEM-1 has persisted as the most frequently encountered bla TEM allele in bacterial populations.

scholarly journals Giardia duodenalis-induced alterations of commensal bacteria killCaenorhabditis elegans: a new model to study microbial-microbial interactions in the gut

2015 ◽  
Vol 308 (6) ◽  
pp. G550-G561 ◽  
Author(s):  
Teklu K. Gerbaba ◽  
Pratyush Gupta ◽  
Kevin Rioux ◽  
Dave Hansen ◽  
Andre G. Buret
Keyword(s):  
Bacterial Colonization ◽  
Giardia Duodenalis ◽  
Microbial Interactions ◽  
Commensal Bacteria ◽  
In Vivo Model ◽  
Functional Changes ◽  
E Coli ◽  
C Elegans ◽  
Human Microbiota

Giardia duodenalis is the most common cause of parasitic diarrhea worldwide and a well-established risk factor for postinfectious irritable bowel syndrome. We hypothesized that Giardia-induced disruptions in host-microbiota interactions may play a role in the pathogenesis of giardiasis and in postgiardiasis disease. Functional changes induced by Giardia in commensal bacteria and the resulting effects on Caenorhabditis elegans were determined. Although Giardia or bacteria alone did not affect worm viability, combining commensal Escherichia coli bacteria with Giardia became lethal to C. elegans. Giardia also induced killing of C. elegans with attenuated Citrobacter rodentium espF and map mutant strains, human microbiota from a healthy donor, and microbiota from inflamed colonic sites of ulcerative colitis patient. In contrast, combinations of Giardia with microbiota from noninflamed sites of the same patient allowed for worm survival. The synergistic lethal effects of Giardia and E. coli required the presence of live bacteria and were associated with the facilitation of bacterial colonization in the C. elegans intestine. Exposure to C. elegans and/or Giardia altered the expression of 172 genes in E. coli. The genes affected by Giardia included hydrogen sulfide biosynthesis (HSB) genes, and deletion of a positive regulator of HSB genes, cysB, was sufficient to kill C. elegans even in the absence of Giardia. Our findings indicate that Giardia induces functional changes in commensal bacteria, possibly making them opportunistic pathogens, and alters host-microbe homeostatic interactions. This report describes the use of a novel in vivo model to assess the toxicity of human microbiota.

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