Antibiofilm Activities of Biogenic Silver Nanoparticles Against Candida albicans

Biofilms are microbial colonies that are encased in an organic polymeric matrix and are resistant to antimicrobial treatments. Biofilms can adhere to both biotic and abiotic surfaces, allowing them to colonize medical equipment such as urinary and intravenous catheters, mechanical heart valves, endotracheal tubes, and prosthetic joints. Candida albicans biofilm is the major etiological cause of the pathogenesis of candidiasis in which its unobstructed growth occurs in the oral cavity; trachea, and catheters that progress to systemic infections in the worst scenarios. There is an urgent need to discover novel biofilm preventive and curative agents. In the present investigation, an effort is made to observe the role of cyanobacteria-derived AgNPs as a new antibiofilm agent with special reference to candidiasis. AgNPs synthesized through the green route using Anabaena variabilis cell extract were characterized by UV–visible spectroscopy. The nanoparticles were spherical in shape with 11–15 nm size and were monodispersed. The minimum inhibitory concentration (MIC) of AgNPs was obtained at 12.5 μg/mL against C. albicans. AgNPs 25 μg/mL showed 79% fungal cell membrane permeability and 22.2% ROS production. AgNPs (25 μg/mL) also facilitated 62.5% of biofilm inhibition and degradation. Therefore, AgNPs could be considered as a promising antifungal agent to control biofilm produced by C. albicans.

Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury

Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage. The clinical and radiologic picture must be distinguished from direct infection of the central nervous system by some viruses, and from metabolic and mitochondrial disorders. Outcomes following ANE are poor overall and worse in those with brainstem involvement. Specific management is often directed toward modulating immune responses given the potential role of systemic inflammation and cytokine storm in potentiating neurologic injury in ANE, though benefits of such approaches remain unclear. The finding that many patients have mutations in the nucleoporin gene RANBP2, which encodes a multifunctional protein that plays a key role in nucleocytoplasmic transport, may allow for the development of disease models that provide insights into pathogenic mechanisms and novel therapeutic approaches.

Multi-layered networks of SalmoNet2 enable strain comparisons of the Salmonella genus on a molecular level

Serovars of the genus Salmonella primarily evolved as gastrointestinal pathogens in a wide range of hosts. Some serotypes later evolved further, adopting a more invasive lifestyle in a narrower host range associated with systemic infections. A system-level knowledge of these pathogens has the potential to identify the complex adaptations associated with the evolution of serovars with distinct pathogenicity, host range and risk to human health. This promises to aid the design of interventions and serve as a knowledge base in the Salmonella research community. Here we present SalmoNet2, a major update to SalmoNet, the first multi-layered interaction resource for Salmonella strains, containing protein-protein, transcriptional regulatory and enzyme-enzyme interactions. The new version extends the number of Salmonella genomes from 11 to 20, including strains such as Salmonella Typhimurium D23580, an epidemic multidrug-resistant strain leading to invasive non-typhoidal Salmonella Disease (iNTS), and a strain from Salmonella bongori, another species in the Salmonella genus. The database now uses strain specific metabolic models instead of a generalised model to highlight differences between strains. This has increased the coverage of high-quality protein-protein interactions, and enhances interoperability with other computational resources by adopting standardised formats. The resource website has been updated with tutorials to help researchers analyse their Salmonella data using molecular interaction networks from SalmoNet2. SalmoNet2 is accessible at http://salmonet.org/.</SPAN>

STANDARDS OF MEDICAL CARE “INVASIVE CANDIDIASIS IN NEWBORNS”

Candida infection (candidiasis) is an important clinical problem in newborns who need treatment in modern intensive care units. Organ and/or systemic infections caused by these fungi are called invasive candidiasis (IC). Newborns are especially vulnerable to IC, and their incidence is 3-5 times higher than the corresponding rates in children or adults. Invasive fungal infections caused by Candida are the third most common late-onset infection in infants born with a birth weight <1500 g. IC in newborns is associated with approximately 20% mortality, and about half of survivors have serious long- term neurological damage. In recent years, new data have been obtained on the diagnosis, prevention and treatment of IC in newborns, which has determined a change in treatment recommendations. Accordingly, the need arose to ensure the compliance of our clinical practice with modern evidence-based approaches. Early diagnosis of candidiasis and prompt treatment with effective antifungal agents such as fluconazole, amphotericin B, and micafungin, when indicated, are critical to improving outcomes.

First Clinical Cases of OXA-48-Producing Klebsiella pneumoniae in Peru

Background: Carbapenemase-producing Enterobacteriaceae (CPE) represents a global public health concern and systemic infections associated with OXA-48 carbapenemase are increasingly being reported in Latin America. Here, we present the first 2 cases of systemic infections by OXA-48-Producing Klebsiella pneumoniae in Peru. A favorable clinical response was observed after targeted treatment with colistin as a backbone.

A GDPase/UDPase Bifunctional Enzyme From Candida Albicans: Purification and Biochemical Characterization

The most frequently isolated human fungal pathogen is Candida albicans which is responsible for about 50% of all Candida infections. In healthy individuals, this organism resides as a part of the normal microbiota in equilibrium with the host. However, under certain conditions, particularly in immunocompromised patients, this opportunistic pathogen adheres to host cells causing serious systemic infections. Thus, much effort has been dedicated to the study of its physiology with emphasis on factors associated to pathogenicity. A representative analysis deals with the mechanisms of glycoprotein assembly as many cell surface antigens and other macromolecules that modulate the immune system fall within this chemical category. In this regard, studies of the terminal protein glycosylation stage which occurs in Golgi vesicles has led to the identification of nucleotidases that convert glycosyltransferase-generated dinucleotides into the corresponding mononucleotides, thus playing a double function: their activity prevent inhibition of further glycosyl transfer by the accumulation of dinucleotides and the resulting mononucleotides are exchanged by specific membrane transporters for equimolecular amounts of sugar donors from the cytosol. Here, using a simple protocol for protein separation we isolated a bifunctional nucleotidase from C. albicans active on GDP and UDP that was characterized in terms of its molecular mass, response to bivalent ions and other factors, substrate specificity and affinity. Results are discussed in terms of the similarities and differences of this nucleotidase with similar counterparts from other organisms thus contributing to the knowledge of a bifunctional diphosphatase not described before in C. albicans.

GP IIb/IIIa-Mediated Platelet Activation and Its Modulation of the Immune Response of Monocytes Against Candida albicans

Candida albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted. Previous studies have identified an essential role of platelets in infection and immunity, especially when they are activated. However, it is still unclear whether platelets can be activated by C. albicans, and even less is known about the role of platelets in C. albicans infection. Herein, we showed that C. albicans induced platelet activation in vitro. C. albicans elevated the levels of AKT Ser473 phosphorylation, and inhibition of the PI3K-AKT signaling pathway reversed C. albicans-induced platelet activation. Surprisingly, C. albicans-induced platelet activation occurred in an integrin glycoprotein (GP) IIb/IIIa-dependent manner but was independent of the pattern recognition receptors toll-like receptor (TLR) 2 and TLR4. Interestingly, platelets enhanced the phagocytosis of human monocytes challenged with C. albicans and upregulated the expression of inflammatory cytokines, which were dependent on platelet activation mediated by GP IIb/IIIa. The present work provides new insights into the role of activated platelets in the defense against C. albicans, highlighting the importance of GP IIb/IIIa in the recognition of C. albicans.

Campylobacter fetus subspecies venerealis meningitis associated with a companion dog in a young adult: a case report

Background Campylobacter spp., common commensals in the gastrointestinal tract of animals, especially poultry, can cause acute gastrointestinal illness in humans through animal-to-human transmission. Although Campylobacter fetus, especially subspecies fetus, rarely leads to systemic infections such as bacteremia in immunocompromised patients, it is unclear whether Campylobacter fetus subspecies venerealis (Cfv) causes infectious diseases in humans. Case presentation A 28-year-old man with a history of chronic alcoholism visited the emergency department with weakness of the left extremities. The patient was clinically diagnosed with community-acquired bacterial meningitis. The organism from the blood culture was subsequently identified as Campylobacter fetus. On phylogenetic analysis, the 16S rRNA sequence showed 99.93% similarity with other Cfv 16S rRNA sequences. The patient had no exposure to identifiable sources except for close contact with a companion dog, which could have been a possible source of transmission. Conclusions This case suggests that Cfv could lead to human systemic infections such as meningitis and that companion animals, in addition to well-known animal hosts, could be sources of transmission.

The Role of a Rapid Prevention of Ralstonia pickettii Growth during Dialysis in a Frail Patient

Ralstonia pickettii is an opportunistic bacillus found in Pseudomonas species, with the ability to induce systemic infections. We report the case of a 69-year-old man, with a clinical history of myeloma, Type IIdiabetes, renal failure (grade IV), and colon cancer, that developed a severe bacterial infection, with acute asthenia and a fever, that appeared at the end of dialysis. Using theMALDI-TOF technology, the bacillus Ralstonia pickettii was identified, and an antimicrobial treatment was quickly started with a rapid microbiological remission.