scholarly journals Potency of gastrointestinal colonization and virulence of Candida auris in a murine endogenous candidiasis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243223
Author(s):  
Masahiro Abe ◽  
Harutaka Katano ◽  
Minoru Nagi ◽  
Yoshitsugu Higashi ◽  
Yuko Sato ◽  
...  

Background Candida auris infections have recently emerged worldwide, and this species is highly capable of colonization and is associated with high levels of mortality. However, strain-dependent differences in colonization capabilities and virulence have not yet been reported. Objectives In the present study, we aimed to clarify the differences between clinically isolated invasive and non-invasive strains of C. auris. Methods We evaluated colonization, dissemination, and survival rates in wild C57BL/6J mice inoculated with invasive or non-invasive strains of C. auris under cortisone acetate immunosuppression, comparing with those of Candida albicans and Candida glabrata infections. We also evaluated the potency of biofilm formation. Results Stool fungal burdens were significantly higher in mice inoculated with the invasive strains than in those infected with the non-invasive strain. Along with intestinal colonization, liver and kidney fungal burdens were also significantly higher in mice inoculated with the invasive strains. In addition, histopathological findings revealed greater dissemination and colonization of the invasive strains. Regarding biofilm-forming capability, the invasive strain of C. auris exhibited a significantly higher capacity of producing biofilms. Moreover, inoculation with the invasive strains resulted in significantly greater loss of body weight than that noted following infection with the non-invasive strain. Conclusions Invasive strains showed higher colonization capability and rates of dissemination from gastrointestinal tracts under cortisone acetate immunosuppression than non-invasive strains, although the mortality rates caused by C. auris were lower than those caused by C. albicans.

2020 ◽  
Vol 21 (16) ◽  
pp. 5834
Author(s):  
Anna Maria Grimaldi ◽  
Silvia Nuzzo ◽  
Gerolama Condorelli ◽  
Marco Salvatore ◽  
Mariarosaria Incoronato

There is an unmet need for novel non-invasive prognostic molecular tumour markers for breast cancer (BC). Accumulating evidence shows that miR-155 plays a pivotal role in tumorigenesis. Generally, miR-155 is considered an oncogenic miRNA promoting tumour growth, angiogenesis and aggressiveness of BC. Therefore, many researchers have focused on its use as a prognostic biomarker and therapeutic target. However, its prognostic value for BC patients remains controversial. To address this issue, the present systematic review aims to summarize the available evidence and give a picture of a prognostic significance of miR-155 in BC pathology. All eligible studies were searched on PubMed and EMBASE databases through various search strategies. Starting from 289 potential eligible records, data were examined from 28 studies, comparing tissue and circulating miR-155 expression levels with clinicopathological features and survival rates in BC patients. We discuss the pitfalls and challenges that need to be assessed to understand the power of miR-155 to respond to real clinical needs, highlighting the consistency, robustness or lack of results obtained to sate in translating this molecule to clinical practice. Our paper suggests that the prognostic role of miR-155 in the management of BC needs to be further verified.


mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Robert W. McKee ◽  
Carissa K. Harvest ◽  
Rita Tamayo

ABSTRACTThe intracellular signaling molecule cyclic diguanylate (c-di-GMP) regulates many processes in bacteria, with a central role in controlling the switch between motile and nonmotile lifestyles. Recent work has shown that inClostridium difficile(also calledClostridioides difficile), c-di-GMP regulates swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we determined the transcriptional regulon of c-di-GMP inC. difficile,employing overexpression of a diguanylate cyclase gene to artificially manipulate intracellular c-di-GMP. Consistent with prior work, c-di-GMP regulated the expression of genes involved in swimming and surface motility. c-di-GMP also affected the expression of multiple genes encoding cell envelope proteins, several of which affected biofilm formationin vitro. A substantial proportion of the c-di-GMP regulon appears to be controlled either directly or indirectly via riboswitches. We confirmed the functionality of 11 c-di-GMP riboswitches, demonstrating their effects on downstream gene expression independent of the upstream promoters. The class I riboswitches uniformly functioned as “off” switches in response to c-di-GMP, while class II riboswitches acted as “on” switches. Transcriptional analyses of genes 3′ of c-di-GMP riboswitches over a broad range of c-di-GMP levels showed that relatively modest changes in c-di-GMP levels are capable of altering gene transcription, with concomitant effects on microbial behavior. This work expands the known c-di-GMP signaling network inC. difficileand emphasizes the role of the riboswitches in controlling known and putative virulence factors inC. difficile.IMPORTANCEInClostridium difficile, the signaling molecule c-di-GMP regulates multiple processes affecting its ability to cause disease, including swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we used RNA-seq to define the transcriptional regulon of c-di-GMP inC. difficile. Many new targets of c-di-GMP regulation were identified, including multiple putative colonization factors. Transcriptional analyses revealed a prominent role for riboswitches in c-di-GMP signaling. Only a subset of the 16 previously predicted c-di-GMP riboswitches were functionalin vivoand displayed potential variability in their response kinetics to c-di-GMP. This work underscores the importance of studying c-di-GMP riboswitches in a relevant biological context and highlights the role of the riboswitches in controlling gene expression inC. difficile.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Lohith Kunyeit ◽  
Nawneet K. Kurrey ◽  
K. A. Anu-Appaiah ◽  
Reeta P. Rao

ABSTRACT Systemic infections of Candida species pose a significant threat to public health. Toxicity associated with current therapies and emergence of resistant strains present major therapeutic challenges. Here, we report exploitation of the probiotic properties of two novel, food-derived yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (strain ApC), as an alternative approach to combat widespread opportunistic fungal infections. Both yeasts inhibit virulence traits such as adhesion, filamentation, and biofilm formation of several non-albicans Candida species, including Candida tropicalis, Candida krusei, Candida glabrata, and Candida parapsilosis as well as the recently identified multidrug-resistant species Candida auris. They inhibit adhesion to abiotic surfaces as well as cultured colon epithelial cells. Furthermore, probiotic treatment blocks the formation of biofilms of individual non-albicans Candida strains as well as mixed-culture biofilms of each non-albicans Candida strain in combination with Candida albicans. The probiotic yeasts attenuated non-albicans Candida infections in a live animal. In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non-albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non-albicans Candida alleviated pathogenic colonization of the nematode gut. The probiotic properties of these novel yeasts are better than or comparable to those of the commercially available probiotic yeast Saccharomyces boulardii, which was used as a reference strain throughout this study. These results indicate that yeasts derived from food sources could serve as an effective alternative to antifungal therapy against emerging pathogenic Candida species. IMPORTANCE Non-albicans Candida-associated infections have emerged as a major risk factor in the hospitalized and immunecompromised patients. Besides, antifungal-associated complications occur more frequently with these non-albicans Candida species than with C. albicans. Therefore, as an alternative approach to combat these widespread non-albicans Candida-associated infections, here we showed the probiotic effect of two yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (ApC), in preventing adhesion and biofilm formation of five non-albicans Candida strains, Candida tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis, and Candida auris. The result would influence the current trend of the conversion of conventional antimicrobial therapy into beneficial probiotic microbe-associated antimicrobial treatment.


2006 ◽  
Vol 75 (1) ◽  
pp. 122-126 ◽  
Author(s):  
Zhi Liu ◽  
Fiona R. Stirling ◽  
Jun Zhu

ABSTRACT Vibrio cholerae, the pathogen that causes cholera, also survives in aqueous reservoirs, probably in the form of biofilms. Quorum sensing negatively regulates V. cholerae biofilm formation through HapR, whose expression is induced at a high cell density. In this study, we show that the concentration of the quorum-sensing signal molecule CAI-1 is higher in biofilms than in planktonic cultures. By measuring hapR expression and activity, we found that the induction of quorum sensing in biofilm-associated cells occurs earlier. We further demonstrate that the timing of hapR expression is crucial for biofilm thickness, biofilm detachment rates, and intestinal colonization efficiency. These results suggest that V. cholerae is able to regulate its biofilm architecture by temporal induction of quorum-sensing systems.


2013 ◽  
Vol 23 (2) ◽  
pp. 66-70
Author(s):  
Albertas Daukša ◽  
Antanas Gulbinas ◽  
Aurelija Kazlauskaitė ◽  
Johannes Oldenburg ◽  
Osman El-Maarri

Gastric cancers are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. For this aim, we investigated tumor suppressor genes CDKN2A/p16, RARBeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 for methylation changes in peripheral blood leukocytes of gastric cancer patients. This study shows that methylation changes in peripheral blood leukocyte DNA could provide a promising method for the early detection of gastric cancer. However, larger studies are essential to explore the clinical usefulness of a peripheral blood leukocyte DNA methylation based tests for non-invasive early detection of gastric cancer.


2003 ◽  
Vol 124 (4) ◽  
pp. A673
Author(s):  
Odd H. Gilja ◽  
Knut Matre ◽  
Aymen B. Ahmed ◽  
Andreas Heimdal ◽  
Trygve Hausken ◽  
...  

2016 ◽  
Vol 79 (7) ◽  
pp. 1127-1134 ◽  
Author(s):  
A. LAMAS ◽  
I. C. FERNANDEZ-NO ◽  
J. M. MIRANDA ◽  
B. VÁZQUEZ ◽  
A. CEPEDA ◽  
...  

ABSTRACT Salmonella serovars are responsible for foodborne diseases around the world. The ability to form biofilms allows microorganisms to survive in the environment. In this study, 73 Salmonella strains, belonging to four different subspecies, were isolated from poultry houses and foodstuffs and tested. Biofilm formation was measured at four different temperatures and two nutrient concentrations. Morphotypes and cellulose production were evaluated at three different temperatures. The presence of several genes related to biofilm production was also examined. All strains and subspecies of Salmonella had the ability to form biofilms, and 46.57% of strains produced biofilms under all conditions tested. Biofilm formation was strain dependent and varied according to the conditions. This is the first study to analyze biofilm formation in a wide number of Salmonella enterica subsp. arizonae strains, and no direct relationship between the high prevalence of Salmonella enterica subsp. arizonae strains and their ability to form biofilm was established. Morphotypes and cellulose production varied as the temperature changed, with 20°C being the optimum temperature for expression of the red, dry, and rough morphotype and cellulose. Salmonella enterica subsp. arizonae, whose morphotype is poorly studied, only showed a smooth and white morphotype and lacked the csgD and gcpA genes that are implicated in biofilm production. Thus, Salmonella biofilm formation under different environmental conditions is a public health problem because it can survive and advance through the food chain to reach the consumer.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2112 ◽  
Author(s):  
Charinya Pimson ◽  
Tipaya Ekalaksananan ◽  
Chamsai Pientong ◽  
Supannee Promthet ◽  
Nuntiput Putthanachote ◽  
...  

Background.Assessment of DNA methylation of specific genes is one approach to the diagnosis of cancer worldwide. Early stage detection is necessary to reduce the mortality rate of cancers, including those occurring in the stomach. For this purpose, tumor cells in circulating blood offer promising candidates for non-invasive diagnosis. Transcriptional inactivation of tumor suppressor genes, likePCDH10andRASSF1A, by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a biomarker.Methods.The present research was conducted to evaluate DNA methylation in these two genes using blood samples of gastric cancer cases. Clinicopathological data were also analyzed and cumulative survival rates generated for comparison.Results.High frequencies ofPCDH10andRASSF1Amethylations in the gastric cancer group were noted (94.1% and 83.2%, respectively, as compared to 2.97% and 5.45% in 202 matched controls). Most patients (53.4%) were in severe stage of the disease, with a median survival time of 8.4 months after diagnosis. Likewise, the patients with metastases, orRASSF1AandPCDH10methylations, had median survival times of 7.3, 7.8, and 8.4 months, respectively. A Kaplan–Meier analysis showed that cumulative survival was significantly lower in those cases positive for methylation ofRASSF1Athan in their negative counterparts. Similarly, whereas almost 100% of patients positive forPCDH10methylation had died after five years, none of the negative cases died over this period. Notably, the methylations ofRASSF1AandPCDH10were found to be higher in the late-stage patients and were also significantly correlated with metastasis and histology.Conclusions.PCDH10andRASSF1Amethylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition toRASSF1Amethylation, tumor stage proved to be a major prognostic factor in terms of survival rates.


Sign in / Sign up

Export Citation Format

Share Document