scholarly journals High-Affinity Transporters for NAD+ Precursors in Candida glabrata Are Regulated by Hst1 and Induced in Response to Niacin Limitation

2009 ◽  
Vol 29 (15) ◽  
pp. 4067-4079 ◽  
Author(s):  
Biao Ma ◽  
Shih-Jung Pan ◽  
Renee Domergue ◽  
Tracey Rigby ◽  
Malcolm Whiteway ◽  
...  

ABSTRACT The yeast Candida glabrata is an opportunistic pathogen of humans. C. glabrata is a NAD+ auxotroph, and its growth depends on the availability of niacin (environmental vitamin precursors of NAD+). We have previously shown that a virulence-associated adhesin, encoded by EPA6, is transcriptionally induced in response to niacin limitation. Here we used transcript profiling to characterize the transcriptional response to niacin limitation and the roles of the sirtuins Hst1, Hst2, and Sir2 in mediating this response. The majority of genes transcriptionally induced by niacin limitation are regulated by Hst1, suggesting that it is the primary sensor of niacin limitation in C. glabrata. We show that three highly induced genes, TNA1, TNR1, and TNR2, encode transporters which are necessary and sufficient for high-affinity uptake of NAD+ precursors. Strikingly, if a tna1 tnr1 tnr2 mutant is starved for niacin, it exhibits an extended lag phase, suggesting a central role for the transporters in restoring NAD+ homeostasis after niacin limitation. Lastly, we had previously shown that the adhesin encoded by EPA6 is induced during experimental urinary tract infection (UTI); we show here that EPA6 transcriptional induction during UTI is strongly enhanced in the tna1 tnr1 tnr2 mutant strain, implicating the transporters in the growth of C. glabrata during infection.

2007 ◽  
Vol 18 (2) ◽  
pp. 149-150 ◽  
Author(s):  
Danny Lagrotteria ◽  
Coleman Rotstein ◽  
Christine H Lee

There has been a gradual increase in the incidence of non-Candida albicans-related nosocomial infections.Candida glabrataurinary tract infections have increased in frequency, and treating these infections can be difficult because the organism may be resistant to fluconazole. A newer antifungal agent, micafungin, which belongs in the class of echinocandins, provides an alternative and effective therapy againstC glabrata. The present report describes three cases ofC glabrata-associated urinary tract infections successfully treated with micafungin. To the authors’ knowledge, this is the first report of successful treatment ofC glabrataand azole-resistantC albicans-associated urinary tract infection with an echinocandin.


2020 ◽  
Vol 11 (1) ◽  
pp. 760-764
Author(s):  
Ahmed Ali Obaid ◽  
Akhlaas Shaker Lateef ◽  
Lina Abdulkadhim Oudah ◽  
Qusay Jabbar Harjan ◽  
Zinah Abdulkadhim Oudah

One hundred diuresis samples were collected from patients with urinary tract infection from Al-Diwaniyah General Teaching Hospital in Al-Diwaniyah city for the period from January 1, 2019, to August 1, 2019, as 35 isolates belonging to the sex of streptococcus were isolated and with an isolation rate of 35% of the total 100 diuresis samples, The yield of 20 isolates to the negative staphylococcus aureus was tested for cocaine, and 5 isolates were of type S. xylosus, with an isolation rate of 25% of the total negative staphylococci for testing cocaine, and by 5% of the total of the reagent samples. These biochemical bacteria were diagnosed using the API Staph system. The clinical stages of the infection are in the subacute or chronic phase without clear symptoms. Streptococcus unproductive streptococcus resistant and anti-life antibody novobiocin, especially S. saprophyticus, are most common in urinary tract infections in immunocompetent patients, and mild infection in women is accompanied by dysuria. Young women between the ages of 16-16 years old to 42%. It affects the ureter in men. It can cause cystitis, pyelonephritis and glomerulonephritis. This group possesses a high affinity to epithelial cells, and this comes from the participation of different proteins such as a 160-Kd protein with Hemagglutinin and Fibriller protein, and it is symbolized by 95-Kd, which is found in 98% of clinical isolates.


Author(s):  
Seyed Reza Aghili ◽  
Mahdi Abastabar ◽  
Ameneh Soleimani ◽  
Iman Haghani ◽  
Soheil Azizi

Background and Purpose: Heart failure is a leading cause of hospitalization, and asymptomatic candiduria is common in hospitalized patients with low morbidity. However, in most patients, it is resolved spontaneously on the removal of the catheter. Despite the publication of guidelines, there are still controversies over the diagnosis and management of candiduria. However, in hospitalized patients with heart failure, the decision to treat candiduria is especially important since the nosocomial infections are associated with an increase in morbidity, mortality, length of hospital stay, and healthcare costs. Some species of Candida, such as Candida glabrata, are increasingly resistant to the first-line and second-line antifungal medications. The present study aimed to investigate the incidence of asymptomatic Candida urinary tract infection due to C. glabrata and antifungal susceptibility of Candida isolates in hospitalized patients with heart failure. Materials and Methods: In total, 305 hospitalized patients with heart failure were studied to identify asymptomatic nosocomial candiduria during 2016-17 in one private hospital in the north of Iran. The Sabouraud’s dextrose agar culture plates with a colony count of >104 colony-forming unit/ml of urine sample were considered as Candida urinary tract infection. Candida species were identified based on the morphology of CHROMagar Candida (manufactured by CHROMagar, France) and PCR-RFLP method with MspI restriction enzyme. Antifungal susceptibility testing of the isolates was performed using five mediations, including itraconazole, voriconazole, fluconazole, amphotericin B, and caspofungin by broth microdilution method according to CLSI M27-S4. Results: In this study, the rate of asymptomatic Candida urinary tract infection was 18.8%, which was more common in people above 51 years old and females (70%). In addition to the urinary and intravascular catheter, the occurrence of candiduria in hospitalized patients had significant relationships with a history of surgical intervention, diastolic heart failure, and use of systemic antibiotics (P>0.05). Among Candida spp., non-albicans Candida species was the most common infectious agent (59.7%). Moreover, C. glabrata (n=27, 40.3%) (alone or with other species) and Candida albicans (n=27, 40.3%) were the most common agents isolated in Candida urinary tract infection. Based on the results of the in vitro susceptibility test, the C. glabrata isolates were 15%, 59%, 70%, 74%, and 85% susceptible to caspofungin, amphotericin B, itraconazole, voriconazole, and fluconazole, respectively. Conclusion: According to the findings, there was a high prevalence of asymptomatic Candida urinary tract infection in hospitalized patients with heart failure. Besides, it was suggested that there was a shift towards non-albicans Candida, especially C. glabrata, in these patients. Therefore, asymptomatic candiduria in hospitalized patients with heart failure should be considered significant. Furthermore, the identification of Candida species along with antifungal susceptibility is essential and helps the clinicians to select the appropriate antifungal agent for better management of such cases.


2018 ◽  
Vol 218 (7) ◽  
pp. 351-355
Author(s):  
G. Jiménez-Guerra ◽  
A. Lara-Oya ◽  
I. Martínez-Egea ◽  
J.M. Navarro-Marí ◽  
J. Gutiérrez-Fernández

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Tijana Markovic ◽  
Taylor Miller-Ensminger ◽  
Adelina Voukadinova ◽  
Alan J. Wolfe ◽  
Catherine Putonti

ABSTRACT Actinomyces neuii is an opportunistic pathogen. Within the urogenital tract, it has been associated with bacterial vaginosis and overactive bladder symptoms. Here, we investigate a draft genome sequence of A. neuii UMB1295, which was isolated from a catheterized urine sample from a woman with a urinary tract infection.


2018 ◽  
Author(s):  
Srijan Jindal ◽  
Harish Thampy ◽  
Philip J. Day ◽  
Douglas B. Kell

AbstractCells ofE. coliwere grown in LB medium, taken from a stationary phase of 2-4h, and reinoculated into fresh media at a concentration (105.mL-1or lower) characteristic of bacteriuria. Flow cytometry was used to assess how quickly we could detect changes in cell size, number, membrane energisation (using a carbocyanine dye) and DNA distribution. It turned out that while the lag phase observable macroscopically via bulk OD measurements could be as long as 4h, the true lag phase could be less than 15-20 min, and was accompanied by many observable biochemical changes. Antibiotics to which the cells were sensitive affected these changes within 20 min of reinoculation, providing the possibility of a very rapid antibiotic susceptibility test, on a timescale compatible with a visit to a GP clinic. The strategy was applied successfully to genuine potential Urinary Tract Infection (UTI) samples taken from a doctor’s surgery. The methods developed could prove of considerable value in ensuring the correct prescription and thereby lowering the spread of antimicrobial resistance.


2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Brenda Yin Qi Tien ◽  
Hwee Mian Sharon Goh ◽  
Kelvin Kian Long Chong ◽  
Soumili Bhaduri-Tagore ◽  
Sarah Holec ◽  
...  

ABSTRACT Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. E. faecalis and E. coli coinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that with E. coli infection alone. Finally, we demonstrated that coinoculation of E. faecalis with a commensal strain of E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support the hypothesis that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensal E. coli strains.


2021 ◽  
Vol 17 (4) ◽  
pp. e1009534
Author(s):  
Cristina Penaranda ◽  
Nicole M. Chumbler ◽  
Deborah T. Hung

Long-term survival of bacterial pathogens during persistent bacterial infections can be associated with antibiotic treatment failure and poses a serious public health problem. Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa, which can cause both acute and chronic infections, are particularly challenging due to its high intrinsic resistance to antibiotics. The ineffectiveness of antibiotics is exacerbated when bacteria reside intracellularly within host cells where they can adopt a drug tolerant state. While the early steps of adherence and entry of P. aeruginosa into mammalian cells have been described, the subsequent fate of internalized bacteria, as well as host and bacterial molecular pathways facilitating bacterial long-term survival, are not well defined. In particular, long-term survival within bladder epithelial cells has not been demonstrated and this may have important implications for the understanding and treatment of UTIs caused by P. aeruginosa. Here, we demonstrate and characterize the intracellular survival of wild type (WT) P. aeruginosa inside bladder epithelial cells and a mutant with a disruption in the bacterial two-component regulator AlgR that is unable to survive intracellularly. Using simultaneous dual RNA-seq transcriptional profiling, we define the transcriptional response of intracellular bacteria and their corresponding invaded host cells. The bacterial transcriptional response demonstrates that WT bacteria rapidly adapt to the stress encountered in the intracellular environment in contrast to ΔalgR bacteria. Analysis of the host transcriptional response to invasion suggests that the NF-ΚB signaling pathway, previously shown to be required for extracellular bacterial clearance, is paradoxically also required for intracellular bacterial survival. Lastly, we demonstrate that intracellular survival is important for pathogenesis of P. aeruginosa in vivo using a model of murine urinary tract infection. We propose that the unappreciated ability of P. aeruginosa to survive intracellularly may play an important role in contributing to the chronicity and recurrence of P. aeruginosa in urinary tract infections.


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