scholarly journals Bifidobacterium adolescentis shows potential to strengthen host defence against gastrointestinal infection via inhibition of the opportunistic pathogen Candida albicans and stimulation of human-isolated macrophages killing capacity in vitro

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Megan D. Lenardon ◽  
Caitlin Jukes ◽  
Ahmed N. Hegazy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Limited Information ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Host Immune Responses ◽  
Opportunistic Fungal Pathogen ◽  
Antimicrobial Metabolites

The human gut microbiota enhances the host’s resistance to enteric pathogens via colonisation resistance, a phenomenon that is driven by multiple mechanisms, such as production of antimicrobial metabolites and activation of host immune responses. However, there is limited information on how individual gut bacterial species, particularly many of the dominant anaerobes, might impact the host’s defence. This study investigated the potential of specific human gut isolates to bolster the host’s resistance to infection. First, by antagonising the opportunistic fungal pathogen Candida albicans, and secondly, by modulating the killing capacity of human-isolated macrophages in vitro. Co-culturing C. albicans with faecal microbiota from different healthy individuals revealed varying levels of fungal inhibition. In vitro assays with a panel of representative human gut anaerobes confirmed that culture supernatants from certain bacterial isolates, in particular of Bifidobacterium adolescentis, significantly inhibited C. albicans growth. Mechanistic studies revealed that microbial fermentation acids including acetate and lactate, in combination with the associated decrease in pH, were strong drivers of this inhibitory activity. In the second in vitro assay, human-isolated macrophages were exposed to bacterial supernatants, and subsequently tested for their capacity to eliminate adherent-invasive Escherichia coli. Among the gut anaerobes tested, B. adolescentis was revealed to exert the strongest immunostimulatory and killing effect when compared to the unstimulated macrophages control. B. adolescentis is known to be stimulated by dietary consumption of resistant starch andmay therefore represent an attractive target for the development of probiotic and prebiotic interventions tailored to enhancethe host’s natural defences against infection.

scholarly journals Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans

2021 ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Gillian E Donachie ◽  
Ambre Chapuis ◽  
Kristyna Mezerova ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Activity ◽  
Fungal Pathogen ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Opportunistic Fungal Pathogen

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via mechanisms such as competition for nutrients and by production of antimicrobial compounds. Here, we investigated the antagonist activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections and mortality in susceptible patients. Co-culture batch incubations of C. albicans in the presence of faecal microbiota from six different healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene sequence profiling of these faecal co-culture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow up mechanistic studies confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro under both aerobic and anaerobic conditions. Production of the fermentation acids acetate and lactate, together with the concomitant decrease in pH, were strong drivers of the inhibitory activity. Bifidobacteria may therefore represent attractive targets for the development of probiotics and prebiotic interventions tailored to enhance inhibitory activity against C. albicans in vivo.

scholarly journals Global Identification of Biofilm-Specific Proteolysis in Candida albicans

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Michael B. Winter ◽  
Eugenia C. Salcedo ◽  
Matthew B. Lohse ◽  
Nairi Hartooni ◽  
Megha Gulati ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Venous Catheter ◽  
Opportunistic Pathogen ◽  
Fungal Species ◽  
Implanted Medical Devices ◽  
Opportunistic Fungal Pathogen ◽  
Biofilm Development

ABSTRACT Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension) state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5) and Sap6 (Candidapepsin-6) as major biofilm-specific proteases secreted by C. albicans . Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation. IMPORTANCE Biofilm formation by the opportunistic fungal pathogen C. albicans is a major cause of life-threatening infections. This work provides a global characterization of secreted proteolytic activity produced specifically by C. albicans biofilms. We identify activity from the proteases Sap5 and Sap6 as highly upregulated during C. albicans biofilm formation and develop Sap-cleavable fluorogenic substrates that enable the detection of biofilms from C. albicans and also from additional pathogenic Candida species. Furthermore, SAP5 and SAP6 deletions confirm that both proteases are required for proper biofilm development in vitro and in vivo . We propose that secreted proteolysis is a promising marker for the diagnosis and potential therapeutic targeting of Candida biofilm-associated infections.

scholarly journals In vitro co-cultures of human gut bacterial species as predicted from co-occurrence network analysis

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0195161 ◽  
Author(s):  
Promi Das ◽  
Boyang Ji ◽  
Petia Kovatcheva-Datchary ◽  
Fredrik Bäckhed ◽  
Jens Nielsen
Keyword(s):  
Network Analysis ◽  
Bacterial Species ◽  
Human Gut

scholarly journals Phytochemical Composition and In Vitro Antimicrobial Activity of Essential Oils from the Lamiaceae Family against Streptococcus agalactiae and Candida albicans Biofilms

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 592
Author(s):  
Ramona Iseppi ◽  
Roberta Tardugno ◽  
Virginia Brighenti ◽  
Stefania Benvenuti ◽  
Carla Sabia ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Essential Oils ◽  
Streptococcus Agalactiae ◽  
Reproductive Tract ◽  
Bacterial Species ◽  
Female Reproductive Tract ◽  
Retention Data ◽  
Natural Defense

The antimicrobial activity of different essential oils (EOs) from the Lamiaceae family was evaluated on Streptococcus agalactiae, Candida albicans, and lactobacilli. S. agalactiae is the main cause of severe neonatal infections, such as sepsis, meningitis, and pneumonia. C. albicans is a primary causative agent of vulvovaginal candidiasis, a multifactorial infectious disease of the lower female reproductive tract. Lactobacilli represent the dominant bacterial species of the vaginal flora and constitute the natural defense against pathogens. On the basis of the preliminary results, the attention was focused on the EOs from Lavandula x intermedia Emeric ex Loisel. and Mentha arvensis L. By using gas ghromatography (GS) retention data and mass spectra, it was possible to identify more than 90% of the total composition of the EO samples. The minimal inhibitory concentration (MIC) and anti-biofilm activity of the two EOs were determined against all isolated strains, using the EOs by themselves or in combination with each other and with drugs (erythromycin and fluconazole). The results showed a good antimicrobial and anti-biofilm activity of both EOs and a synergistic effect, leading to the best results against all the strains, resulted using the combinations EOs/EOs and antimicrobials/EOs.

scholarly journals Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes

Microbiology ◽  
2010 ◽  
Vol 156 (2) ◽  
pp. 392-399 ◽  
Author(s):  
Jennifer L. Patterson ◽  
Annica Stull-Lane ◽  
Philippe H. Girerd ◽  
Kimberly K. Jefferson
Keyword(s):  
Bacterial Vaginosis ◽  
Cytotoxic Activity ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Collective Effects ◽  
Gardnerella Vaginalis ◽  
Childbearing Age ◽  
Virulence Potential ◽  
Virulence Properties

Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder in women of childbearing age. BV is characterized by a dramatic shift in the vaginal microflora, involving a relative decrease in lactobacilli, and a proliferation of anaerobes. In most cases of BV, the predominant bacterial species found is Gardnerella vaginalis. However, pure cultures of G. vaginalis do not always result in BV, and asymptomatic women are sometimes colonized with low numbers of G. vaginalis. Thus, there is controversy about whether G. vaginalis is an opportunistic pathogen and the causative agent of many cases of BV, or whether BV is a polymicrobial condition caused by the collective effects of an altered microbial flora. Recent studies of the biofilm-forming potential and cytotoxic activity of G. vaginalis have renewed interest in the virulence potential of this organism. In an effort to tease apart the aetiology of this disorder, we utilized in vitro assays to compare three virulence properties of G. vaginalis relative to other BV-associated anaerobes. We designed a viable assay to analyse bacterial adherence to vaginal epithelial cells, we compared biofilm-producing capacities, and we assessed cytotoxic activity. Of the BV-associated anaerobes tested, only G. vaginalis demonstrated all three virulence properties combined. This study suggests that G. vaginalis is more virulent than other BV-associated anaerobes, and that many of the bacterial species frequently isolated from BV may be relatively avirulent opportunists that colonize the vagina after G. vaginalis has initiated an infection.

scholarly journals Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

2016 ◽  
Vol 113 (50) ◽  
pp. E8141-E8150 ◽  
Author(s):  
Tze Guan Tan ◽  
Esen Sefik ◽  
Naama Geva-Zatorsky ◽  
Lindsay Kua ◽  
Debdut Naskar ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Bacterial Species ◽  
Alternative Mechanism ◽  
Filamentous Bacteria ◽  
Transcriptional Program ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Gut Epithelium ◽  
Cell Accumulation

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particularBifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB,B. adolescentiswas closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However,B. adolescentiselicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice withB. adolescentisexacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that includeBifidobacteriumstrains also drove intestinal Th17 cell accumulation.

scholarly journals Poly (acetyl arginyl) glucosamine attenuates Pseudomonas aeruginosa in a rat lung infection model

2021 ◽  
Author(s):  
Bryan Garcia ◽  
Melissa S. McDaniel ◽  
Allister J. Loughran ◽  
J. Dixon Johns ◽  
Vidya Narayanaswamy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Respiratory Infections ◽  
Bacterial Species ◽  
Membrane Integrity ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Total Biomass ◽  
Chronic Infections

Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer which has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity which can normalize rheologic properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, which may warrant further evaluation as a therapeutic.

scholarly journals Decreased Ecological Resistance of the Gut Microbiota in Response to Clindamycin Challenge in Mice Colonized with the Fungus Candida albicans

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Laura Markey ◽  
Antonia Pugliese ◽  
Theresa Tian ◽  
Farrah Roy ◽  
Kyongbum Lee ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Gut Microbiota ◽  
Bacterial Species ◽  
Species Abundance ◽  
Alpha Diversity ◽  
Human Gut ◽  
Content Type ◽  
Ecological Resistance ◽  
Bacterial Microbiota ◽  
Host Health

ABSTRACT The mammalian gut microbiota is a complex community of microorganisms which typically exhibits remarkable stability. As the gut microbiota has been shown to affect many aspects of host health, the molecular keys to developing and maintaining a “healthy” gut microbiota are highly sought after. Yet, the qualities that define a microbiota as healthy remain elusive. We used the ability to resist change in response to antibiotic disruption, a quality we refer to as ecological resistance, as a metric for the health of the bacterial microbiota. Using a mouse model, we found that colonization with the commensal fungus Candida albicans decreased the ecological resistance of the bacterial microbiota in response to the antibiotic clindamycin such that increased microbiota disruption was observed in C. albicans-colonized mice compared to that in uncolonized mice. C. albicans colonization resulted in decreased alpha diversity and small changes in abundance of bacterial genera prior to clindamycin challenge. Strikingly, co-occurrence network analysis demonstrated that C. albicans colonization resulted in sweeping changes to the co-occurrence network structure, including decreased modularity and centrality and increased density. Thus, C. albicans colonization resulted in changes to the bacterial microbiota community and reduced its ecological resistance. IMPORTANCE Candida albicans is the most common fungal member of the human gut microbiota, yet its ability to interact with and affect the bacterial gut microbiota is largely uncharacterized. Previous reports showed limited changes in microbiota composition as defined by bacterial species abundance as a consequence of C. albicans colonization. We also observed only a few bacterial genera that were significantly altered in abundance in C. albicans-colonized mice; however, C. albicans colonization significantly changed the structure of the bacterial microbiota co-occurrence network. Additionally, C. albicans colonization changed the response of the bacterial microbiota ecosystem to a clinically relevant perturbation, challenge with the antibiotic clindamycin.

scholarly journals Flexible Cobamide Metabolism in Clostridioides (Clostridium) difficile 630 Δerm

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Amanda N. Shelton ◽  
Xun Lyu ◽  
Michiko E. Taga
Keyword(s):  
De Novo ◽  
Aminolevulinic Acid ◽  
Genomic Analysis ◽  
Opportunistic Pathogen ◽  
Vitamin B ◽  
Uptake System ◽  
Human Gut ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides (Clostridium) difficile is an opportunistic pathogen known for its ability to colonize the human gut under conditions of dysbiosis. Several aspects of its carbon and amino acid metabolism have been investigated, but its cobamide (vitamin B12 and related cofactors) metabolism remains largely unexplored. C. difficile has seven predicted cobamide-dependent pathways encoded in its genome in addition to a nearly complete cobamide biosynthesis pathway and a cobamide uptake system. To address the importance of cobamides to C. difficile, we studied C. difficile 630 Δerm and mutant derivatives under cobamide-dependent conditions in vitro. Our results show that C. difficile can use a surprisingly diverse array of cobamides for methionine and deoxyribonucleotide synthesis and can use alternative metabolites or enzymes, respectively, to bypass these cobamide-dependent processes. C. difficile 630 Δerm produces the cobamide pseudocobalamin when provided the early precursor 5-aminolevulinic acid or the late intermediate cobinamide (Cbi) and produces other cobamides if provided an alternative lower ligand. The ability of C. difficile 630 Δerm to take up cobamides and Cbi at micromolar or lower concentrations requires the transporter BtuFCD. Genomic analysis revealed genetic variations in the btuFCD loci of different C. difficile strains, which may result in differences in the ability to take up cobamides and Cbi. These results together demonstrate that, like other aspects of its physiology, cobamide metabolism in C. difficile is versatile. IMPORTANCE The ability of the opportunistic pathogen Clostridioides difficile to cause disease is closely linked to its propensity to adapt to conditions created by dysbiosis of the human gut microbiota. The cobamide (vitamin B12) metabolism of C. difficile has been underexplored, although it has seven metabolic pathways that are predicted to require cobamide-dependent enzymes. Here, we show that C. difficile cobamide metabolism is versatile, as it can use a surprisingly wide variety of cobamides and has alternative functions that can bypass some of its cobamide requirements. Furthermore, C. difficile does not synthesize cobamides de novo but produces them when given cobamide precursors. A better understanding of C. difficile cobamide metabolism may lead to new strategies to treat and prevent C. difficile-associated disease.

scholarly journals Two Routes of Metabolic Cross-Feeding between Bifidobacterium adolescentis and Butyrate-Producing Anaerobes from the Human Gut

2006 ◽  
Vol 72 (5) ◽  
pp. 3593-3599 ◽  
Author(s):  
Alvaro Belenguer ◽  
Sylvia H. Duncan ◽  
A. Graham Calder ◽  
Grietje Holtrop ◽  
Petra Louis ◽  
...  
Keyword(s):  
Pure Culture ◽  
Dietary Carbohydrates ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Acetyl Coenzyme A ◽  
End Products ◽  
Pure Cultures ◽  
Human Large Intestine ◽  
Eubacterium Hallii

ABSTRACT Dietary carbohydrates have the potential to influence diverse functional groups of bacteria within the human large intestine. Of 12 Bifidobacterium strains of human gut origin from seven species tested, four grew in pure culture on starch and nine on fructo-oligosaccharides. The potential for metabolic cross-feeding between Bifidobacterium adolescentis and lactate-utilizing, butyrate-producing Firmicute bacteria related to Eubacterium hallii and Anaerostipes caccae was investigated in vitro. E. hallii L2-7 and A. caccae L1-92 failed to grow on starch in pure culture, but in coculture with B. adolescentis L2-32 butyrate was formed, indicating cross-feeding of metabolites to the lactate utilizers. Studies with [13C]lactate confirmed carbon flow from lactate, via acetyl coenzyme A, to butyrate both in pure cultures of E. hallii and in cocultures with B. adolescentis. Similar results were obtained in cocultures involving B. adolescentis DSM 20083 with fructo-oligosaccharides as the substrate. Butyrate formation was also stimulated, however, in cocultures of B. adolescentis L2-32 grown on starch or fructo-oligosaccharides with Roseburia sp. strain A2-183, which produces butyrate but does not utilize lactate. This is probably a consequence of the release by B. adolescentis of oligosaccharides that are available to Roseburia sp. strain A2-183. We conclude that two distinct mechanisms of metabolic cross-feeding between B. adolescentis and butyrate-forming bacteria may operate in gut ecosystems, one due to consumption of fermentation end products (lactate and acetate) and the other due to cross-feeding of partial breakdown products from complex substrates.

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