The ‘Metabolic Trap’: Candida parapsilosis Inhibits Staphylococcus aureus Biofilm Maturation by Disrupting pH Homeostasis and Inducing Premature Exodus
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ABSTRACT:
ORGANISM(S): Staphylococcus aureus
PROVIDER: GSE334781 | GEO | 2026/06/23
REPOSITORIES: GEO
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Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic.
2014-07-21 | GSE57451 | GEO
Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic. C. parapsilosis mRNA profiles of wild type (WT) at 37 degree celcius in planktonic growth conditions and ace2-/-, cph2-/-, efg1-/-, czf1-/-, ume6-/-, bcr1-/- and WT in biofilm conditions were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
2014-07-21 | E-GEOD-57451 | biostudies-arrayexpress
Project description:Staphylococcus aureus is a notorious biofilm-producing pathogen that is frequently isolated from implantable medical device infections. As biofilm ages, it becomes more tolerant to antimicrobial treatment leading to treatment failure and necessitating the costly removal of infected devices. In this study, we investigated what changes occur in the proteome of S. aureus biofilm grown for 3-days and 12-days in comparison with 24 h planktonic showed that proteins associated with bi-osynthetic processes, ABC transporter pathway, virulence proteins, and shikimate kinase pathway were significantly upregulated in 3-day biofilm, while proteins associated with sugar transporter, degradation, and stress response were downregulated. In 12-day biofilms, proteins associated with peptidoglycan biosynthesis, sugar transporters, and stress responses were upregulated, whereas proteins associated with ABC transporters, DNA replication, and adhesion proteins were down-regulated. Furthermore, we observed significant variations in the formation of biofilms result from changes in the level of metabolic activity in the different growth mode of biofilms that could be a significant factor of S. aureus biofilm maturation and persistence. Collectively, potential marker proteins were identified and further characterized to understand their exact role in S. aureus biofilm development which may shed light on possible new therapeutic regimes in the treatment of biofilm-related implant-associated infections.
2022-08-12 | PXD033499 | Pride
Project description:Biofilms are ubiquitous in natural, medical, and engineering environments. While most antibiotics that primarily aim to inhibit cell growth may result in bacterial drug resistance, biofilm inhibitors do not affect cell growth and there is less chance of developing resistance. This work sought to identify novel, non-toxic and potent biofilm inhibitors from Streptomyces bacteria for reducing the biofilm formation of Pseudomonas aeruginosa PAO1. Out of 4300 Streptomyces strains, one species produced and secreted peptide(s) to inhibit P. aeruginosa biofilm formation by 93% without affecting the growth of planktonic cells. Global transcriptome analyses (DNA microarray) revealed that the supernatant of the Streptomyces 230 strain induced phenazine, pyoverdine, and pyochelin synthesis genes. Electron microscopy showed that the supernatant of Streptomyces 230 strain reduced the production of polymeric matrix in P. aeruginosa biofilm cells, while the Streptomyces species enhanced swarming motility of P. aeruginosa. Therefore, current study suggests that Streptomyces bacteria are an important resource of biofilm inhibitors as well as antibiotics.
2013-03-21 | GSE28194 | GEO
Project description:<p>The food safety landscape faces a significant challenge from methicillin-resistant Staphylococcus aureus (MRSA), a virulent and antibiotic-resistant foodborne pathogen. This study investigates the antimicrobial properties and mechanisms of cell-free supernatant (CFS) from Bifidobacterium longum FB1-4 against MRSA. The CFS exhibited robust antibacterial activity, achieving a minimum inhibitory concentration (MIC) of 5.56 mg/ml and maintaining a bacterial elimination rate of over 80% for 8 hours at 2× MIC, demonstrating superior sustained bactericidal efficacy compared to vancomycin. Antibacterial component analysis revealed that while the initial effect is partly pH-dependent, the activity is largely attributable to heat-stable molecules, retaining 90% efficacy after high-temperature treatment. In a food matrix, FB1-4 CFS exhibited impressive bactericidal effects against three MRSA strains, leading to elimination rates of 94.64% at 2 hours, 98.02% at 4 hours, 99.90% at 6 hours, and nearly complete eradication (99.99%) by 8 hours. Furthermore, FB1-4 CFS significantly suppressed all three tested MRSA strains (MRSA-43300, MRSA-337371, and MRSA-361194); P<0.05) mecA expression, increased antibiotic susceptibility, and diminished biofilm formation by 70%. Transcriptomic and metabolomic analyses revealed that FB1-4 CFS modulates two-component systems and quorum sensing, leading to reduced virulence factor expression. In vivo studies confirmed a 90% reduction in MRSA colonization in mouse intestines. These findings provide critical insights into how probiotic metabolites inhibit MRSA, underscoring their potential as natural therapeutic agents in food safety.</p>
2026-02-26 | MTBLS13481 | MetaboLights
Project description:Is there a universal genetically programmed defense providing tolerance to antibiotics when bacteria grow as biofilms? A comparison between biofilms of three different bacterial species by transcriptomic and metabolomic approaches uncovered no evidence of one. Single-species biofilms of three bacterial species (Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii) were grown in vitro for three days then challenged with respective antibiotics (ciprofloxacin, daptomycin, tigecycline) for an additional 24 h. All three microorganisms displayed reduced susceptibility in biofilms compared to planktonic cultures. Global transcriptomic profiling of gene expression comparing biofilm to planktonic and antibiotic-treated biofilm to untreated biofilm was performed. Extracellular metabolites including 18 amino acids, glucose, lactate, acetate, formate, and ethanol were measured to characterize the utilization of carbon sources between biofilms, treated biofilms, and planktonic cells. While all three bacteria exhibited a species-specific signature of stationary phase, no conserved gene, gene set, or common functional pathway could be identified that changed consistently across the three microorganisms. Across the three species, glucose consumption was increased in biofilms compared to planktonic cells and alanine and aspartic acid utilization were decreased in biofilms compared to planktonic cells. The reasons for these changes were not readily apparent in the transcriptomes. No common shift in the utilization pattern of carbon sources was discerned when comparing untreated to antibiotic-exposed biofilms. Overall, our measurements do not support the existence of a common genetic or biochemical basis for biofilm tolerance against antibiotics. Rather, there are likely myriad genes, proteins, and metabolic pathways that influence the physiological state of microorganisms in biofilms contributing to antibiotic tolerance. The Staphylococcus aureus microarray data from the study described above is deposited here.
2021-10-18 | GSE185864 | GEO
Project description:Biofilm-related diseases are typically persistent infections, and a challenge for medical treatment. Biofilms are communities of bacteria that attach to surfaces and are enclosed in an extracellular matrix. These sessile microorganisms can endure external stresses like nutrient deprivation, antibiotic treatments, and immune defences. Therefore, biofilms create conditions favourable for bacterial pathogenesis. The knowledge of novel biofilm regulators may contribute to develop new strategies to fight microbial infections. In this work we study the role of the RNA-binding protein and RNA-degradative enzyme polynucleotide phosphorylase (PNPase) from the human pathogen Listeria monocytogenes. We show that inactivation of Listeria PNPase not only leads to strong defects in biofilm production, but also affects biofilm morphology. RNA-seq analysis of the RNA extracted from biofilms of the wild-type and the PNPase mutant strains revealed major changes in the expression of genes affecting the metabolism of carbon. Lastly, infection assays in eukaryotic cell lines confirmed that PNPase deletion leads to the severe attenuation of Listeria monocytogenes pathogenicity. Overall, our results show that PNPase is a novel regulator of biofilm formation and human cellular invasion of a bacterial pathogen. This work presents PNPase as a new and attractive target for the control of bacterial infection and highlights the expanding role of RNA-binding proteins as critical players in pathogenicity.
2023-06-05 | GSE210097 | GEO
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals. Host genetics influence the susceptibility to S. aureus infections, and genes determining infection outcome remain to be identified. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated in vitro how mammary epithelial cells (MEC) respond to live S. aureus or S. aureus supernatant and whether MEC from animals with different degree of susceptibility to intra-mammary infections have distinct gene expression profiles. We measured the expression of 15K probes in MEC after each kind of stimulation (living bacteria or culture supernatant) at three different time points (a reference without bacteria, 1 and 5 hours) with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated MEC were obtained and genes involved in the cell cycle and metabolic processes were down-regulated during the kinetics and the apoptosis pathways were highly modified after both live bacteria and supernatant stimulations. Genes involved in immune response were up-regulated over-all after supernatant exposure. Furthermore 23 genes were differentially expressed between the resistant and susceptible animals, two of them were involed in oxidative processes, but the differences between the animals were very few. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine MEC in a 5 hour kinetics experiment. The in vitro MEC model does not provide much information on the differences between Staphylococcus resistant and susceptible animals. Keywords: Staphylococcus aureus ; mammary epithelial cells ; mammalian ; transcriptome ; immunity ; mastitis
2012-03-01 | GSE30390 | GEO
Project description:Staphylococcus aureus is a major opportunistic pathogen and notable efforts are currently under way to develop new methods to combat staphylococcal infections. It is becoming increasingly clear that understanding the ecology of pathogenic bacteria is important to design improved disinfection and therapeutic strategies. Like many microbes, S. aureus commonly forms biofilms on various biotic and abiotic surfaces. Also, most isolates are known to carry prophages in their genomes. With this in mind, it seems that acquiring a better knowledge of the impact of prophages on the physiology of S. aureus biofilm cells would be useful for the development of strategies to eliminate this pathogen from industrial and hospital surfaces or human tissues. Here, we examined the impact of lysogeny on the transcriptome of S. aureus cells during biofilm development. The observed changes in gene expression indicated activation of the regulon controlled by the alternative sigma factor SigB. This response, typically triggered by stress conditions, leads to a greater production of the carotenoid pigment staphyloxanthin and a reduced production of extracellular proteins involved in biofilm dispersion. Overall, this study lays the foundations for characterizing the complex molecular interactions between temperate staphylophages and their host, and understanding their impact on microbial community dynamics.
2018-08-20 | GSE111012 | GEO
Project description:Staphylococcus aureus is an important human pathogen that causes life-threatening infections, and is resistant to the majority of our antibiotic arsenal. This resistance is complicated by the observation that most antibacterial agents target actively growing cells, thus, proving ineffective against slow growing populations, such as cells within a biofilm or in stationary phase. Recently, our group generated updated genome annotation files for S. aureus that not only include protein-coding genes but also regulatory and small RNAs. As such, these annotation files were used to perform a transcriptomic analysis in order to understand the metabolic and physiological changes that occur during transition from active growth to stationary phase; with a focus on sRNAs. We observed â¼24% of protein-coding and 34% of sRNA genes displaying changes in expression by â¥3-fold. Collectively, this study adds to our understanding of S. aureus adaptation to nutrient-limiting conditions, and sheds new light onto the contribution of sRNAs to this process. Bacterial cells were grown in TSB medium at 37°C with shaking for 3h (exponential growth phase) or 16h (stationary growth phase).
2016-05-18 | E-GEOD-77242 | biostudies-arrayexpress