scholarly journals Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Kara R. Eichelberger ◽  
James E. Cassat
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Secondary Infection ◽  
Microbial Metabolism ◽  
Toxin Production ◽  
Metabolic Changes ◽  
Host Cells

Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site can further influence the metabolic processes required for a pathogen to cause disease. The Gram-positive bacterium Staphylococcus aureus and the polymorphic fungus Candida albicans are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, S. aureus and C. albicans are frequently co-isolated from mixed fungal-bacterial infections. S. aureus and C. albicans co-infection alters microbial metabolism relative to infection with either organism alone. Metabolic changes during co-infection regulate virulence, such as enhancing toxin production in S. aureus or contributing to morphogenesis and cell wall remodeling in C. albicans. C. albicans and S. aureus also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The S. aureus and C. albicans metabolic programs induced during co-infection impact interactions with host immune cells, resulting in greater microbial survival and immune evasion. Conversely, innate immune cell sensing of S. aureus and C. albicans triggers metabolic changes in the host cells that result in an altered immune response to secondary infections. In this review article, we discuss the metabolic programs that govern host-pathogen interactions during S. aureus and C. albicans co-infection. Understanding C. albicans-S. aureus interactions may highlight more general principles of how polymicrobial interactions, particularly fungal-bacterial interactions, shape the outcome of infectious disease. We focus on how co-infection alters microbial metabolism to enhance virulence and how infection-induced changes to host cell metabolism can impact a secondary infection.

scholarly journals Candida albicans and Staphylococcus aureus Pathogenicity and Polymicrobial Interactions: Lessons beyond Koch’s Postulates

2019 ◽  
Vol 5 (3) ◽  
pp. 81 ◽  
Author(s):  
Olivia A. Todd ◽  
Brian M Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Sequence Data ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Microbial Interactions ◽  
Human Pathogens ◽  
Koch’S Postulates ◽  
Bacterial Interaction ◽  
Koch's Postulates

While Koch’s Postulates have established rules for microbial pathogenesis that have been extremely beneficial for monomicrobial infections, new studies regarding polymicrobial pathogenesis defy these standards. The explosion of phylogenetic sequence data has revolutionized concepts of microbial interactions on and within the host. However, there remains a paucity of functional follow-up studies to delineate mechanisms driven by such interactions and how they shape health or disease. That said, one particular microbial pairing, the fungal opportunist Candida albicans and the bacterial pathogen Staphylococcus aureus, has received much attention over the last decade. Therefore, the objective of this review is to discuss the multi-faceted mechanisms employed by these two ubiquitous human pathogens during polymicrobial growth, including how they: establish and persist in inter-Kingdom biofilms, tolerate antimicrobial therapy, co-invade host tissue, exacerbate quorum sensing and staphylococcal toxin production, and elicit infectious synergism. Commentary regarding new challenges and remaining questions related to future discovery of this fascinating fungal–bacterial interaction is also provided.

scholarly journals Candida albicans Impacts Staphylococcus aureus Alpha-Toxin Production via Extracellular Alkalinization

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Olivia A. Todd ◽  
Mairi C. Noverr ◽  
Brian M. Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Extracellular Ph ◽  
Morbidity And Mortality ◽  
Alpha Toxin ◽  
Content Type

ABSTRACT Candida albicans and Staphylococcus aureus are common causes of nosocomial infections with severe morbidity and mortality. Murine polymicrobial intra-abdominal infection (IAI) with C. albicans and S. aureus results in acute mortality dependent on the secreted cytolytic effector alpha-toxin. Here, we confirmed that alpha-toxin is elevated during polymicrobial growth compared to monomicrobial growth in vitro. Therefore, this study sought to unravel the mechanism by which C. albicans drives enhanced staphylococcal alpha-toxin production. Using a combination of functional and genetic approaches, we determined that an intact agr quorum sensing regulon is necessary for enhanced alpha-toxin production during coculture and that a secreted candidal factor likely is not implicated in elevating agr activation. As the agr system is pH sensitive, we observed that C. albicans raises the pH during polymicrobial growth and that this correlates with increased agr activity and alpha-toxin production. Modulation of the pH could predictably attenuate or activate agr activity during coculture. By using a C. albicans mutant deficient in alkalinization (stp2Δ/Δ), we confirmed that modulation of the extracellular pH by C. albicans can drive agr expression and toxin production. Additionally, the use of various Candida species (C. glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, and C. krusei) demonstrated that those capable of raising the extracellular pH correlated with elevated agr activity and alpha-toxin production during coculture. Overall, we demonstrate that alkalinization of the extracellular pH by the Candida species leads to sustained activation of the staphylococcal agr system. IMPORTANCE Candida albicans and Staphylococcus aureus are commonly coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Thus, they represent a significant cause of nosocomial morbidity and mortality. Yet how these organisms behave in the context of polymicrobial growth remains poorly understood. In this work, we set out to determine the mechanism by which activation of the staphylococcal agr quorum sensing system and production of its major virulence effector alpha-toxin is enhanced during coculture with C. albicans. Surprisingly, we likely ruled out that a secreted candidal factor drives this process. Instead, we demonstrated that alkalinization of the extracellular milieu by C. albicans and other Candida species correlated with elevated agr activity. Thus, we propose a mechanism where modulation of the extracellular pH by fungal opportunists can indirectly alter virulence of a bacterial pathogen. Uncovering molecular events that drive interkingdom pathogenicity mechanisms may enhance surveillance and treatment for devastating polymicrobial infections.

scholarly journals Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

2021 ◽  
Author(s):  
Rita Pombinho ◽  
Jorge Pinheiro ◽  
Mariana Resende ◽  
Diana Meireles ◽  
Sirpa Jalkanen ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Scavenger Receptor ◽  
Protective Role ◽  
Host Cells ◽  
Cell Trafficking ◽  
Host Cell Membrane ◽  
Chemokine Production

ABSTRACTScavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation and cancer, however its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane.We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.

Ceramide in bacterial infections and cystic fibrosis

2008 ◽  
Vol 389 (11) ◽  
Author(s):  
Heike Grassmé ◽  
Katrin Anne Becker ◽  
Yang Zhang ◽  
Erich Gulbins
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
De Novo ◽  
Acid Sphingomyelinase ◽  
Temporal Organization ◽  
Host Cells ◽  
Host Responses ◽  
Mammalian Host ◽  
Membrane Domains

AbstractCeramide is formed by the activity of sphingomyelinases, by degradation of complex sphingolipids, reverse ceramidase activity orde novosynthesized. The formation of ceramide within biological membranes results in the formation of large ceramide-enriched membrane domains. These domains serve the spatial and temporal organization of receptors and signaling molecules. The acid sphingomyelinase-ceramide system plays an important role in the infection of mammalian host cells with bacterial pathogens such asNeisseria gonorrhoeae,Escherichia coli,Staphylococcus aureus,Listeria monocytogenes,Salmonella typhimuriumandPseudomonas aeruginosa. Ceramide and ceramide-enriched membrane platforms are also involved in the induction of apoptosis in infected cells, such as in epithelial and endothelial cells after infection withPseudomonas aeruginosaandStaphylococcus aureus, respectively. Finally, ceramide-enriched membrane platforms are critical regulators of the release of pro-inflammatory cytokines upon infection. The diverse functions of ceramide in bacterial infections suggest that ceramide and ceramide-enriched membrane domains are key players in host responses to many pathogens and thus are potential novel targets to treat infections.

scholarly journals Schistosome immunomodulators

2021 ◽  
Vol 17 (12) ◽  
pp. e1010064
Author(s):  
Sreemoyee Acharya ◽  
Akram A. Da’dara ◽  
Patrick J. Skelly
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Natural Infection ◽  
Host Cells ◽  
Anionic Polymer ◽  
Th2 Response ◽  
Anti Inflammatory ◽  
The Impact

Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the “alarmin” ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2—that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules—protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.

Analysis of the Bacterial Vesicles' Enhanced Toxicological Threat Via Electron Microscopy

2017 ◽  
pp. 19-43
Author(s):  
Roberta Curia ◽  
Marziale Milani ◽  
Lyubov V Didenko ◽  
George A Avtandilov ◽  
Natalia V Shevlyagina ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Plastic Material ◽  
Membrane Vesicles ◽  
Host Cells ◽  
Dental Prostheses ◽  
Bacterial Secretion

This study shows the importance of electron microscopy in the analysis of the interaction of microorganisms (Staphylococcus aureus) with polymeric (polyurethane) dental prostheses. Starting from the biofilm formation and the biodestruction of the plastic material resulting in the production of polyurethane nanoparticles, the focus is on the bacterial secretion of membrane vesicles (in the range of 20-50 nm) loaded with plastic nanoparticles (from 2-3 to 10 nm) and on the toxicological threat that these delivery devices represent when interacting with host cells. The nanoparticles deliverance led by the bacterial infections dynamics opens new ways to the possibility of delivering drugs to selected cells.

scholarly journals New insights into the pathogenesis of leprosy: contribution of subversion of host cell metabolism to bacterial persistence, disease progression, and transmission

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 70 ◽  
Author(s):  
Cristiana Santos de Macedo ◽  
Flavio Alves Lara ◽  
Roberta Olmo Pinheiro ◽  
Veronica Schmitz ◽  
Marcia de Berrêdo-Pinho ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Immune Responses ◽  
Schwann Cells ◽  
Immune Modulation ◽  
Fatty Acid Biosynthesis ◽  
Cell Metabolism ◽  
Clinical Signs ◽  
Metabolic Changes ◽  
Host Cells ◽  
Lipid Mediator

Chronic infection by the obligate intracellular pathogen Mycobacterium leprae may lead to the development of leprosy. Of note, in the lepromatous clinical form of the disease, failure of the immune system to constrain infection allows the pathogen to reproduce to very high numbers with minimal clinical signs, favoring transmission. The bacillus can modulate cellular metabolism to support its survival, and these changes directly influence immune responses, leading to host tolerance, permanent disease, and dissemination. Among the metabolic changes, upregulation of cholesterol, phospholipids, and fatty acid biosynthesis is particularly important, as it leads to lipid accumulation in the host cells (macrophages and Schwann cells) in the form of lipid droplets, which are sites of polyunsaturated fatty acid–derived lipid mediator biosynthesis that modulate the inflammatory and immune responses. In Schwann cells, energy metabolism is also subverted to support a lipogenic environment. Furthermore, effects on tryptophan and iron metabolisms favor pathogen survival with moderate tissue damage. This review discusses the implications of metabolic changes on the course of M. leprae infection and host immune response and emphasizes the induction of regulatory T cells, which may play a pivotal role in immune modulation in leprosy.

scholarly journals Identification of Effectors of Synergistic Lethality in Candida albicans-Staphylococcus aureus Polymicrobial Intra-abdominal Infection

2021 ◽  
Author(s):  
◽  
Olivia Todd ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Candida Species ◽  
Toxin Production ◽  
Extracellular Ph ◽  
Abdominal Infection ◽  
Intra Abdominal Infection

Candida albicans, an opportunistic fungal pathogen, and Staphylococcus aureus, a ubiquitous pathogenic bacterium, are among the most prevalent causes of nosocomial infections and cause severe morbidity and mortality. Moreover, they are frequently coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Relatively little is known about the complex interactions and signaling events that occur between microbes and even less so how microbial “cross-talk” shapes human health and disease. Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown that coinfection with C. albicans and S. aureus leads to synergistic lethality whereas monomicrobial infection is nonlethal. Therefore, we aimed to identify staphylococcal virulence determinants that drive lethal synergism in polymicrobial IAI. Using the toxigenic S. aureus strain JE2, we observed that co-infection with C. albicans led to a striking 80-100% mortality rate within 20 h p.i while monomicrobial infections were non-lethal. Use of a GFP-P3 promoter S. aureus reporter strain revealed enhanced activation of the staphylococcal agr quorum sensing system during in vitro polymicrobial versus monomicrobial growth. Analyses by qPCR, Western blot, and toxin functional assays confirmed enhanced agr-associated gene transcription and increases in secreted α- and δ-toxins. C. albicans-mediated elevated toxin production and hemolytic activity was determined to be agrA-dependent and genetic knockout and complementation of hla identified ⍺-toxin as the key staphylococcal virulence factor driving lethal synergism. Analysis of mono- and polymicrobial infection 8 h p.i. demonstrated equivalent bacterial burden in the peritoneal cavity, but significantly elevated levels of α-toxin (3-fold) and the eicosanoid PGE2 (4-fold) during co-infection. Importantly, prophylactic passive vaccination using the monoclonal anti-⍺-toxin antibody MEDI4893* led to significantly improved survival rates as compared to treatment with isotype control antibody. Collectively, these results define α-toxin as an essential virulence determinant during C. albicans-S. aureus IAI and describe a novel mechanism by which a human pathogenic fungus can augment the virulence of a highly pathogenic bacterium in vivo. We next sought to unravel the mechanism by which C. albicans drives enhanced staphylococcal ⍺-toxin production. Using a combination of functional and genetic approaches, we determined that an intact agr quorum sensing regulon is necessary for enhanced ⍺-toxin production during coculture and that a secreted candidal factor likely is not implicated in elevating agr activation. As the agr system is pH sensitive, we observed that C. albicans raises the pH during polymicrobial growth and that this correlates with increased agr activity and ⍺-toxin production. By using a C. albicans mutant deficient in alkalinization (stp2Δ/Δ), we confirmed that modulation of the extracellular pH by C. albicans can drive agr expression and toxin production. Additionally, the use of various Candida species (C. glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, and C. krusei) demonstrated that those capable of raising the extracellular pH correlated with elevated agr activity and ⍺-toxin production during coculture. Overall, we demonstrated that alkalinization of the extracellular pH by the Candida species leads to sustained activation of the staphylococcal agr system. Finally, we correlated ⍺-toxin production with significant increases in biomarkers of liver and kidney damage during coinfection and determined that functional toxin was required for morbidity and mortality. We next sought to determine the candidal effector(s) mediating this enhanced virulence by employing an unbiased screening approach. C. albicans transcription factor mutants were evaluated for their ability to induce S. aureus agr activation in polymicrobial culture. Incredibly, we identified several mutants that displayed defects in augmenting S. aureus agr activity in vitro. Two of the mutants failed to completely synergize with S. aureus in vivo and further analysis revealed the necessity of the uncharacterized C. albicans transcription factor, ZCF13, in driving enhanced toxin production both in vitro and in vivo. Collectively, we identified a novel effector by which C. albicans augments S. aureus virulence and identified a potential mechanism of fungal-bacterial lethal synergism.

Screening and antimicrobial activity of actinomycetes isolated from the rhizosphere of Clitoria ternatea

2016 ◽  
Vol 1 (01) ◽  
Author(s):  
Vemavarapu Bhaskara Rao ◽  
Kandlagunta Guru Prasad ◽  
Krishna Naragani ◽  
Vijayalakshmi Muvva
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Calcium Carbonate ◽  
Rhizosphere Soil ◽  
Soil Samples ◽  
Antimicrobial Spectrum ◽  
Clitoria Ternatea ◽  
Primary Screening

The air dried rhizosphere soil samples pretreated with calcium carbonate was employed for the isolation of actinomycete strains. Serial dilution plate technique was used for the isolation of actinomycetes. A total of 20 actinomycete strains designated as BS1-BS20 were isolated from the rhizosphere of medicinal plant Clitoria ternatea. All the 20 strains were subjected to primary screening for antimicrobial activity. Among the 20 strains screened, 10 strains exhibited high antimicrobial spectrum against Staphylococcus aureus, Escherichia coli and Candida albicans.

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