Adaptor Molecules Epitranscriptome Reprograms Bacterial Pathogenicity

The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.

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Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽

10.1186/s40168-021-01027-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Orit Malka ◽

Dorin Kalson ◽

Karin Yaniv ◽

Reut Shafir ◽

Manikandan Rajendran ◽

...

Keyword(s):

Quorum Sensing ◽

Gut Microbiome ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Human Microbiome ◽

Cell Communication ◽

Probiotic Yeast ◽

Gut Pathogen ◽

Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

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Gut Feeling

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1860 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S504-S505

Author(s):

C. Cotta ◽

G. Jesus ◽

V. Vila Nova ◽

C. Moreira

Keyword(s):

Mental Disorders ◽

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Infections ◽

Human Microbiome ◽

Dietary Interventions ◽

Scientific Databases ◽

Antibiotic Drugs ◽

Microbiome Research ◽

Competing Interest

IntroductionThere is growing evidence of the importance of nutrition in mental disorders. Gut microbiota, influenced by environmental factors such as diet and stress, has been proposed as one of the players on a dynamic called gut-brain axis, which is thought to have an influence on behaviour and mental health.Objectives and aimsTo summarize recent evidence on the topic, and its potential role in psychiatric interventions.MethodsThe authors review updated literature collected from online scientific databases.ResultsThe development of the brain itself has been shown to be influenced by the gut microbiome. Research demonstrates that the composition of the microbiota has influence on behaviour through neuroendocrine and other neuroactive messengers production by the bacteria within the gut lumen. Studies in germ-free animals, animals exposed to bacterial infections, probiotic suplements or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. The gut microbiome has been implicated in brain disorders including anxiety and depression, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and autism.ConclusionsThe treatment of mental disorders is usually based on pharmacological and psychotherapeutic interventions, and little attention is given to dietary interventions. The emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans, and points new strategies for developing novel therapeutics for mental disorders.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Differential expression of microRNAs in porcine placentas on Days 30 and 90 of gestation

Reproduction Fertility and Development ◽

10.1071/rd10046 ◽

2010 ◽

Vol 22 (8) ◽

pp. 1175 ◽

Cited By ~ 29

Author(s):

Lijie Su ◽

Shuhong Zhao ◽

Mengjin Zhu ◽

Mei Yu

Keyword(s):

Differential Expression ◽

Differentially Expressed ◽

Locked Nucleic Acid ◽

Chain Reaction ◽

Stem Loop ◽

Non Invasive ◽

Differentially Expressed Mirnas ◽

Non Coding Rnas ◽

Polymerase Chain ◽

And Function

The porcine placenta is classified as a non-invasive epitheliochorial type. To meet the increasing demands for nutrients by the rapidly growing conceptus and/or fetus, the placental microscopic folds undergo significant morphological and biochemical changes during two periods critical for conceptus and/or fetus, namely Days 30–40 and after Day 90 of gestation. MicroRNAs (miRNAs) are a class of small non-coding RNAs that can modulate gene activity by inhibiting the translation or regulation of mRNA degradation. In the present study, we identified 17 differentially expressed miRNAs in porcine placenta on Days 30 and 90 of gestation using a locked nucleic acid (LNA) microRNA array. Stem–loop real-time reverse transcription–polymerase chain reaction confirmed the differential expression of eight selected miRNAs (miR-24, miR-125b, miR-92b, miR-106a, miR-17, let-7i, miR-27a and miR-20). Analysis of targets and the pathways in which these miRNAs are involved revealed that the differentially expressed miRNAs target many genes that are important in various processes, including cell growth, trophoblast differentiation, angiogenesis and formation and maintenance of adherens junctions. The results of the present study suggest potential roles for these differentially expressed miRNAs in porcine placental growth and function.

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Diversity of Aerobic Bacteria Isolated from Oral and Cloacal Cavities from Free-Living Snakes Species in Costa Rica Rainforest

International Scholarly Research Notices ◽

10.1155/2017/8934285 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Allan Artavia-León ◽

Ariel Romero-Guerrero ◽

Carolina Sancho-Blanco ◽

Norman Rojas ◽

Rodolfo Umaña-Castro

Keyword(s):

Costa Rica ◽

Bacterial Infections ◽

Bacterial Species ◽

Ribosomal Database Project ◽

Opportunistic Pathogens ◽

Bacterial Taxonomy ◽

Free Living ◽

16S Rdna Pcr ◽

Animal Bites ◽

Species Specific

Costa Rica has a significant number of snakebites per year and bacterial infections are often complications in these animal bites. Hereby, this study aims to identify, characterize, and report the diversity of the bacterial community in the oral and cloacal cavities of venomous and nonvenomous snakes found in wildlife in Costa Rica. The snakes where captured by casual encounter search between August and November of 2014 in the Quebrada González sector, in Braulio Carrillo National Park. A total of 120 swabs, oral and cloacal, were taken from 16 individuals of the Viperidae and Colubridae families. Samples were cultured on four different media at room temperature. Once isolated in pure culture, colonies were identified with the VITEK® 2C platform (bioMérieux). In order to test the identification provided on environmental isolates, molecular analyses were conducted on 27 isolates of different bacterial species. Specific 16S rDNA PCR-mediated amplification for bacterial taxonomy was performed, then sequenced, and compared with sequences of Ribosomal Database Project (RDP). From 90 bacterial isolates, 40 different bacterial species were identified from both oral and cloacal swabs. These results indicate the diversity of opportunistic pathogens present and their potential to generate infections and zoonosis in humans.

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The Origin of Periodontal Infections

Advances in Dental Research ◽

10.1177/08959374880020020901 ◽

1988 ◽

Vol 2 (2) ◽

pp. 245-259 ◽

Cited By ~ 110

Author(s):

R.J. Genco ◽

J.J. Zambon ◽

L.A. Christersson

Keyword(s):

Bacterial Infections ◽

Periodontal Diseases ◽

Periodontal Pathogens ◽

Opportunistic Pathogens ◽

Oral Flora ◽

Periodontal Infection ◽

Localized Juvenile Periodontitis ◽

Oral Pathogens ◽

Bacteroides Gingivalis

Periodontal diseases are recognized as bacterial infections, and some forms are associated with specific organisms, such as Actinobacillus actinomycetemcomitans in juvenile periodontitis, and Bacteroides gingivalis and others in adult periodontitis. The source of the periodontal organisms, whether they are part of the indigenous or resident flora and overgrow to become opportunistic oral pathogens, or whether they are exogenous oral pathogens, is important to determine. The chain of periodontal infection, microbial agent(s) and their transmission, and host response are reviewed with respect to the role of A. actinomycetemcomitans in localized juvenile periodontitis and B. gingivalis in adult periodontitis. The present data lead us to hypothesize that some periodontal organisms may be exogenous pathogens. Prevention of periodontal diseases may be influenced by the knowledge of whether various forms are caused by opportunistic organisms or exogenous pathogens. If exogenous pathogens are responsible, prevention can be directed to intercepting transmission, thereby preventing colonization. On the other hand, if the organisms are opportunistic pathogens, prevention might be directed at interfering with initial acquisition of the flora earlier in life, as well as suppressing them to low levels consistent with health. For those exogenous periodontal infections, attempts at eradication and prevention of re-infection are likely to be effective. If the organisms are part of the indigenous flora, there is little hope of complete elimination of the organism. Criteria for distinguishing exogenous periodontal pathogens from opportunistic periodontal pathogens include the prediction that exogenous pathogens would be transient members of the oral flora associated with periodontal disease, likely to be comprised of one or a few clonal types, and intrinsically virulent. In contrast, opportunistic periodontal pathogens would likely be members of the indigenous flora and would overgrow. They would likely be comprised of many clonal types, and have an intrinsically low level of virulence.

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Molecular mechanism of bacterial type 1 and P pili assembly

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2013.0153 ◽

2015 ◽

Vol 373 (2036) ◽

pp. 20130153 ◽

Cited By ~ 13

Author(s):

Andreas Busch ◽

Gilles Phan ◽

Gabriel Waksman

Keyword(s):

Molecular Mechanism ◽

Bacterial Infections ◽

Catalytic Mechanism ◽

Bacterial Pathogenicity ◽

Adhesive Surface ◽

Pilus Biogenesis ◽

Tract Infections ◽

New Generation

The formation of adhesive surface structures called pili or fimbriae (‘bacterial hair’) is an important contributor towards bacterial pathogenicity and persistence. To fight often chronic or recurrent bacterial infections such as urinary tract infections, it is necessary to understand the molecular mechanism of the nanomachines assembling such pili. Here, we focus on the so far best-known pilus assembly machinery: the chaperone–usher pathway producing the type 1 and P pili, and highlight the most recently acquired structural knowledge. First, we describe the subunits' structure and the molecular role of the periplasmic chaperone. Second, we focus on the outer-membrane usher structure and the catalytic mechanism of usher-mediated pilus biogenesis. Finally, we describe how the detailed understanding of the chaperone–usher pathway at a molecular level has paved the way for the design of a new generation of bacterial inhibitors called ‘pilicides’.

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Extracellular RNAs in Bacterial Infections: From Emerging Key Players on Host-Pathogen Interactions to Exploitable Biomarkers and Therapeutic Targets

International Journal of Molecular Sciences ◽

10.3390/ijms21249634 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9634

Author(s):

Tiago Pita ◽

Joana R. Feliciano ◽

Jorge H. Leitão

Keyword(s):

Bacterial Infections ◽

Membrane Vesicles ◽

Cellular Functions ◽

Extracellular Medium ◽

Diagnostic Strategies ◽

Key Players ◽

Host Pathogen ◽

Non Coding Rnas ◽

Eukaryotic Organisms ◽

Novel Therapeutic

Non-coding RNAs (ncRNAs) are key regulators of post-transcriptional gene expression in prokaryotic and eukaryotic organisms. These molecules can interact with mRNAs or proteins, affecting a variety of cellular functions. Emerging evidence shows that intra/inter-species and trans-kingdom regulation can also be achieved with exogenous RNAs, which are exported to the extracellular medium, mainly through vesicles. In bacteria, membrane vesicles (MVs) seem to be the more common way of extracellular communication. In several bacterial pathogens, MVs have been described as a delivery system of ncRNAs that upon entry into the host cell, regulate their immune response. The aim of the present work is to review this recently described mode of host-pathogen communication and to foster further research on this topic envisaging their exploitation in the design of novel therapeutic and diagnostic strategies to fight bacterial infections.

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