scholarly journals Toxoflavin secreted by Pseudomonas alcaliphila inhibits growth of Legionella pneumophila and its host Vermamoeba vermiformis

2022 ◽  
Author(s):  
Sebastien P. Faucher ◽  
Sara Matthews ◽  
Arvin Nickzad ◽  
Passoret Vounba ◽  
Deeksha Shetty ◽  
...  

Legionella pneumophila is a natural inhabitant of water systems. From there, it can be transmitted to humans by aerosolization resulting in severe pneumonia. Most large outbreaks are caused by cooling towers contaminated with L. pneumophila. The resident microbiota of the cooling tower is a key determinant for the colonization and growth of L. pneumophila. The genus Pseudomonas correlates negatively with the presence of L. pneumophila, but it is not clear which species is responsible. Therefore, we identified the Pseudomonas species inhabiting 14 cooling towers using a Pseudomonas-specific 16S rRNA amplicon sequencing strategy. Cooling towers free of L. pneumophila contained a high relative abundance of members from the Pseudomonas alcaliphila/oleovorans phylogenetic cluster. In vitro, P. alcaliphila JCM 10630 inhibited the growth of L. pneumophila on agar plates. Analysis of the P. alcaliphila genome revealed the presence of a genes cluster predicted to produce toxoflavin. L. pneumophila growth was inhibited by pure toxoflavin and by extract from P. alcaliphila culture found to contain toxoflavin by LC-ESI-MS. In addition, toxoflavin inhibits growth of Vermameoba vermiformis, a host cell of L. pneumophila. Our study indicates that P. alcaliphila may be important to restrict growth of L. pneumophila in water systems through the production of toxoflavin. A sufficiently high concentration is likely not achieved in the bulk water but might have a local inhibitory effect such as in biofilm.

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Kiran Paranjape ◽  
Émilie Bédard ◽  
Deeksha Shetty ◽  
Mengqi Hu ◽  
Fiona Chan Pak Choon ◽  
...  

Abstract Background Cooling towers are a major source of large community-associated outbreaks of Legionnaires’ disease, a severe pneumonia. This disease is contracted when inhaling aerosols that are contaminated with bacteria from the genus Legionella, most importantly Legionella pneumophila. How cooling towers support the growth of this bacterium is still not well understood. As Legionella species are intracellular parasites of protozoa, it is assumed that protozoan community in cooling towers play an important role in Legionella ecology and outbreaks. However, the exact mechanism of how the eukaryotic community contributes to Legionella ecology is still unclear. Therefore, we used 18S rRNA gene amplicon sequencing to characterize the eukaryotic communities of 18 different cooling towers. The data from the eukaryotic community was then analysed with the bacterial community of the same towers in order to understand how each community could affect Legionella spp. ecology in cooling towers. Results We identified several microbial groups in the cooling tower ecosystem associated with Legionella spp. that suggest the presence of a microbial loop in these systems. Dissolved organic carbon was shown to be a major factor in shaping the eukaryotic community and may be an important factor for Legionella ecology. Network analysis, based on co-occurrence, revealed that Legionella was correlated with a number of different organisms. Out of these, the bacterial genus Brevundimonas and the ciliate class Oligohymenophorea were shown, through in vitro experiments, to stimulate the growth of L. pneumophila through direct and indirect mechanisms. Conclusion Our results suggest that Legionella ecology depends on the host community, including ciliates and on several groups of organisms that contribute to its survival and growth in the cooling tower ecosystem. These findings further support the idea that some cooling tower microbiomes may promote the survival and growth of Legionella better than others.


2019 ◽  
Author(s):  
Adriana Torres Paniagua ◽  
Kiran Paranjape ◽  
Mengqi Hu ◽  
Émilie Bédard ◽  
Sébastien Faucher

ABSTRACTLegionella pneumophila (Lp) is a waterborne bacterium known for causing Legionnaires’ Disease, a severe pneumonia. Cooling towers are a major source of outbreaks, since they provide ideal conditions for Lp growth and produce aerosols. In such systems, Lp typically grow inside protozoan hosts. Several abiotic factors such as water temperature, pipe material and disinfection regime affect the colonization of cooling towers by Lp. The local physical and biological factors promoting the growth of Lp in water systems and its spatial distribution are not well understood. Therefore, we built a lab-scale cooling tower to study the dynamics of Lp colonization in relationship to the resident microbiota and spatial distribution. The pilot was filled with water from an operating cooling tower harboring low levels of Lp. It was seeded with Vermamoeba vermiformis, a natural host of Lp, and then inoculated with Lp. After 92 days of operation, the pilot was disassembled, the water was collected, and biofilm was extracted from the pipes. The microbiome was studied using 16S rRNA and 18S rRNA genes amplicon sequencing. The communities of the water and of the biofilm were highly dissimilar. The relative abundance of Legionella in water samples reached up to 11% whereas abundance in the biofilm was extremely low (≤0.5 %). In contrast, the host cells were mainly present in the biofilm. This suggest that Lp grows in host cells associated with biofilm and is then released back into the water following host cell lysis. In addition, water temperature shaped the bacterial and eukaryotic community of the biofilm, indicating that different parts of the systems may have different effects on Legionella growth.


2019 ◽  
Author(s):  
Kiran Paranjape ◽  
Émilie Bédard ◽  
Lyle G. Whyte ◽  
Jennifer Ronholm ◽  
Michèle Prévost ◽  
...  

ABSTRACTLegionnaire’s Disease (LD) is a severe pneumonia caused byLegionella pneumophila. Cooling towers are the main source ofL. pneumophiladuring large outbreaks. Colonization, survival, and proliferation ofL. pneumophilain cooling towers are necessary for outbreaks to occur. These steps are affected by chemical and physical parameters of the cooling tower environment. We hypothesize that the bacterial community residing in the cooling tower could also affect the presence ofL. pneumophila. A16S rRNAtargeted amplicon sequencing approach was used to study the bacterial community of cooling towers and its relationship with theLegionella spp.andL. pneumophilacommunities. The results indicated that the water source shaped the bacterial community of cooling towers. Several taxa were enriched and positively correlated withLegionella spp.andL. pneumophila. In contrast,Pseudomonasshowed a strong negative correlation withLegionella spp.and several other genera. Most importantly, continuous chlorine application reduced microbial diversity and promoted the presence ofPseudomonascreating a non-permissive environment forLegionella spp. This suggests that disinfection strategies as well as the resident microbial population influences the ability ofLegionella spp.to colonize cooling towers.


Author(s):  
MUNEHIRO YAMAGUCHI ◽  
AKIHIKO TANAKA ◽  
SHIN OHTA ◽  
TAKUYA YOKOE ◽  
YOSHITAKA YAMAMOTO ◽  
...  

1999 ◽  
Vol 44 (5) ◽  
pp. 693-695 ◽  
Author(s):  
A. Tsakris ◽  
S. Alexiou-Daniel ◽  
E. Souliou ◽  
A. Antoniadis

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hong Mei Li ◽  
Jin Kyu Kim ◽  
Jai Man Jang ◽  
Sang Oh Kwon ◽  
Cheng Bi Cui ◽  
...  

To evaluate the aldose reductase (AR) enzyme inhibitory ability ofPrunella vulgarisL. extract, six compounds were isolated and tested for their effects. The components were subjected toin vitrobioassays to investigate their inhibitory assays using rat lens aldose reductase (rAR) and human recombinant AR (rhAR). Among them, caffeic acid ethylene ester showed the potent inhibition, with the IC50values of rAR and rhAR at3.2±0.55 μM and12.58±0.32 μM, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, this compound showed noncompetitive inhibition against rhAR. Furthermore, it inhibited galactitol formation in a rat lens incubated with a high concentration of galactose. Also it has antioxidative as well as advanced glycation end products (AGEs) inhibitory effects. As a result, this compound could be offered as a leading compound for further study as a new natural products drug for diabetic complications.


2021 ◽  
Vol 11 ◽  
Author(s):  
Tuersunayi Abudureheman ◽  
Jing Xia ◽  
Ming-Hao Li ◽  
Hang Zhou ◽  
Wei-Wei Zheng ◽  
...  

B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL.


2020 ◽  
Vol 8 (5) ◽  
pp. 623
Author(s):  
Ka-Lung Lam ◽  
Wai-Yin Cheng ◽  
Fan Yang ◽  
Shaoling Lin ◽  
Lijun You ◽  
...  

We proposed a framework with parametric modeling to obtain biological relevant parameters from the total probiotic growth pattern and metabolite production curves. The lag phase, maximum increase rate, and maximum capacity were obtained via a 205-h exploratory In vitro fermentation of a library of 13 structural-characterized prebiotic candidates against an exclusively breastfed infant fecal inoculum. We also conducted 16S rRNA amplicon sequencing of the infant fecal inoculum. Moreover, we introduce a robust composite metabolite-based indicator that reflects the eubiosis/dysbiosis of microbiota to complement the conventional microbial markers. In terms of short-chain fatty acid, we discovered that polymeric beta-glucans from barley demonstrated potential as prebiotic candidates, while alpha-glucans as glycogen showed the least dissolved ammonia production. In terms of total probiotic, beta-glucans from oat and mushroom sclerotia of Pleurotus tuber-regium showed comparable sustainability when compared to alpha-glucans after 48 h. Being classical prebiotic, galacto-oligosaccharides gave the second-highest metabolite-based indicator, followed by lactose. While limited improvement could be made to lactose and oligosaccharides, polymeric beta-glucans from barley avails more capacity for novel prebiotic development, such as structural modification. We anticipate that more similar parallel screening with the element of time and parametric modeling will provide more novel insights.


2020 ◽  
Vol 367 (16) ◽  
Author(s):  
Pauline Bondue ◽  
Sarah Lebrun ◽  
Bernard Taminiau ◽  
Nadia Everaert ◽  
Gisele LaPointe ◽  
...  

ABSTRACT The ‘first 1000 days of life’ determine the gut microbiota composition and can have long-term health consequences. In this study, the simulator of the human intestinal microbial ecosystem (SHIME®) model, which represents the main functional sections of the digestive tract, was chosen to study the microbiota of young children. The aim of this study was to reproduce the digestive process of toddlers and their specific colonic environment. The ascending, transverse and descending colons of SHIME® model were inoculated with feces from three donors aged between 1 and 2 years-old, in three separate runs. For each run, samples from colon vessels were collected at days 14, 21 and 28 after microbiota stabilization period. Short chain fatty acid concentrations determined by HPLC showed that microbiota obtained in SHIME® model shared characteristics between adults and infants. In addition, microbial diversity and bacterial populations determined by 16S rRNA amplicon sequencing were specific to each colon vessel. In conclusion, the SHIME® model developed in this study seemed well adapted to evaluate prebiotic and probiotic impact on the specific microbiota of toddlers, or medicine and endocrine disruptor metabolism. Moreover, this study is the first to highlight some biofilm development in in vitro gastrointestinal modelling systems.


Author(s):  
Sabuktagin Rahman ◽  
Guus A. M. Kortman ◽  
Jos Boekhorst ◽  
Patricia Lee ◽  
Moududur R. Khan ◽  
...  

Abstract Purpose Adverse effects of iron fortification/supplements such as Micronutrient Powder (MNP) on gut microbiota have previously been found in infection-prone African settings. This study examined the adversaries of a low-iron MNP compared with the standard MNP on the composition of gut microbiota in Bangladeshi children exposed to a high concentration of iron from potable groundwater. Methods A randomized controlled trial was conducted in 2- to 5-year-old children, drinking groundwater with a high concentration of iron (≥ 2 mg/L). Children were randomized to receive one sachet per day of either standard MNP (12.5 mg iron) or low-iron MNP (5 mg iron), for 2 months. A sub-sample of 53 children was considered for paired assessment of the gut microbiome by 16S rRNA amplicon sequencing. Results At baseline, the gut microbiota consisted of Bifidobacteriaceae (15.6%), Prevotellaceae (12.2%), Lactobacillaceae (3.6%), Clostridiaceae (4.1%) and Enterobacteriaceae (2.8%). Overall, there was no significant treatment effect of the low-iron MNP compared to the standard MNP. However, an apparent treatment effect was observed in children with a relative adult-like microbiota, with a higher relative abundance of potentially pathogenic Enterobacteriaceae after receiving the standard MNP compared to the low-iron MNP. This effect, however, was statistically non-significant (p = 0.07). Conclusion In Bangladeshi children drinking iron-rich groundwater, a low-iron MNP supplementation did not have a significant impact on their gut microbiota profile/composition compared to the standard MNP. The trial registration number is ISRCTN60058115; Date of registration 03/07/2019; retrospectively registered.


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