Cause Of Infections Research Articles

Tropical eosinophilia: Case series on varying presentations

ABSTRACT Eosinophilia can be due to both infectious and non-infectious causes, many of which may be clinically indistinguishable. Filariasis, a tropical and subtropical infection, is caused by Wuchereria bancrofti, Brugia timori (B. timori), and Brugia malayi. Filariasis is conventionally diagnosed by demonstration of microfilaria in the peripheral blood smear. The disease may be missed if one is not aware of the possibility. We report two cases in two individuals with eosinophilia due to filaria resulting in tropical pulmonary eosinophilia and deep vein thrombosis (DVT). They had complete symptomatic improvement after a 3-week course of diethylcarbamazine (DEC) +/- ivermectin.

Laryngotracheal stenosis: a single-center retrospective analysis of endoscopic treatment strategies and recurrence.

Laryngotracheal stenosis is a process of fibrosis that results in airway obstruction; it may be congenital or acquired. Acquired cases are due to iatrogenic, traumatic, infectious and autoimmune causes. Patients present with a spectrum of breathing difficulties that might be fatal. This article presents a unique retrospective cross-sectional study of patients with laryngotracheal stenosis who had endoscopic dilatation, and some had open surgical procedures to describe the evolution after the therapy, to compare the outcomes of the dilatation in comparison to surgical interventions and associated complications in other studies, to provide knowledge to help in dealing with these patients, and to enable educated, independent patient decision-making. In this observational and descriptive study, we aimed to highlight the clinical features, management, and treatment outcomes among twenty-nine patients with laryngotracheal stenosis who were managed by open and endoscopic surgical intervention over a period of 5 years. Data were collected retrospectively from the patients' medical records from February 2016 until July 2022 at a hospital in Jerusalem, which is a tertiary healthcare facility and the only referral center for similar cases from the West Bank, East Jerusalem, and Gaza, with a population of around 8 million. Tables and graphs are used to highlight the statistical study's findings. Data were analyzed using Microsoft Excel software. Twenty-nine patients were involved in the study, with an average age of 32.2 years; 51.7% of them were males. The patients had one or more chronic conditions, such as hypertension and coronary artery disease. The majority of patients (65.5%) had stenosis as a result of orotracheal intubation, and the most common site was the subglottic (68.9%). According to the Cotton-Myer classification, 44.8% of the patients were classified in grade III, 34.4% were included in grade I, 13.7% in grade II, and 6.8% in grade IV. Six patients (20.68%) received surgery for stenosis, and 23 patients had an endo-laryngeal dilatation. Restenosis happened in (58.6%). Mortality rates are almost negligible. Subglottic stenosis is still a challenging condition to manage. The authors describe a single-center experience approach dealing with these conditions. Long-term follow-up for these cases is mandatory as the recurrence rate is still high.

Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.

Evaluation of the Relationship Between Bacterial Infection and Immunological Factors with Diabetic Foot Ulcer

Diabetes represent a chronic disorder that involve the decline in the levels of insulin produced by the pancreas due to many genetic and environmental factors. The disease involves the elevation of blood sugar in the circulation which may lead to vascular, neurological, ocular and renal complications. In addition, diabetic patients tend to develop ulceration due to wound infection swiftly in the lower limbs due to the reduce in the neurological sensation as well as to elevated sugar circulation which may greatly provoke wound infection and diabetic foot ulcerations. The current study aimed at isolation of the common causes of bacterial infection associated with diabetic foot ulcer as well as the assessment of IL-17 and IL-18 and in those patients and in control healthy group. The present study was conducted in Salah Aldeen province during the period from 1st of November 2023 to 15th of May 2024 and included 150 patients with diabetic foot infection who attended Salah-Alden Hospitals: (Tikrit Teaching Hospital, Balad General Hospital and private surgery clinics). Swabs and whole blood from patients with diabetic foot ulcer were taken and submitted to routine culture and identification of the causative bacterial infection followed by biochemical identification and antibiotics susceptibility test for the isolated microbe. The serum specimens from those positive bacterial isolates were submitted for IL17 and IL-18 ELISA assessment. IL-17, significant elevation P<0.05 of this cytokine was recorded in diabetic patients with foot ulcer with mean 21.94 pg/ml compared to control group. In the same way significant increase of IL-18 (P<0.05) was noted in diabetic patients with foot ulcer with mean 347.15 pg/ml in comparison to control group. In conclusion, diabetic foot ulceration is the result of in controlled elevation of blood glucose and bacterial infection with various pathogens can complicate the scenario, and the significant elevation of IL17 and IL18 in those patients can insight the role played by these cytokines in signaling the immune to recruit cellular and humoral response.

Complications and long-term impact of early life pneumonia.

Pneumonia is an infection affecting the lower airway, where the air sacs are filled with mucus and pus; and typically presents with cough, fever, and fast breathing. Pneumonia is estimated to be the leading cause of mortality in children under five worldwide with 120 million episodes result in 1 million deaths globally. The Low-Income and Middle-Income Countries (LMICs) are more affected. In a study in southeast Nigeria, bronchopneumonia accounted for 41.9%, of the cases admitted in the tertiary hospitals and in another hospital based study among children, pneumonia had the highest respiratory admission rates at 34.0%. Pneumonia can be caused by various organisms: Bacterial (Streptococcus, staphylococcus etc), Viral (RSV) and recently COVID 19 pneumonia. RSV has been noted globally to be a major cause of childhood lower respiratory tract infection, with morbidity/mortality occurring in 99% of (LMICs). Some of the long term sequalae are discussed.

Ethanolic Extract from Echinacea purpurea (L.) Moench Inhibits Influenza A/B and Respiratory Syncytial Virus Infection in vitro: Preventive Agent for Viral Respiratory Infections.

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods.

Etiology Causes of the Chronic Diarrheal Infection in Children Aged Under Five Years in Salah Al-Din Government

Diarrhea is a factor contributing to both death and illness among children below the age of five in poor nations. Childhood mortality from diarrhea surpasses that of malaria, HIV/AIDS, and measles. The objective of this study was to evaluate the frequency of diarrhea and its related determinants among children aged below five years. The study included collecting 100 stool from children with chronic diarrhea and some other intestinal disorders who came to the hospitals of Salah al-Din Governorate / Dhuluiya District and some private laboratories, whose ages ranged from one month to 36 months during the period between the beginning of December 2023 and the end of June 2024. Males had a higher frequency of diarrheal infection than females, and age groups (1-12)months were more infected than others (p-value< 0.05). Increasing bacterial and fungal illness in weight group (7-11) and cold in this age. Diarrhea from food contamination and unhealthy food increases in 2-6) and 7-11-kg children. As well as cold-induced diarrhea (2-6Kg), p>0.05. This study concluded bacterial infection more common cause of diarrheal infection than other cause, and male more infected than female. In addition increase incidence in age groups (months). Furthermore mixed infection with gram positive and negative more common than only gram positive and negative alone.

Greenish discoloration due to gel nail extensions mimicking Pseudomonas aeruginosa infection: Is beauty really worth the risk: A case report

Over the past decades, the commercialization of nail cosmetics has increased. From nail polishes to artificial nails, different methods of nail beautification have emerged. Knowledge of the safety and efficacy of nail products is very important as nail products such as nail polish, nail polish removers, and artificial nails have several adverse effects. Harmful substances such as toluene sulfonamide-formaldehyde resin and methacrylates have been identified in commercial nail products, leading to several adverse effects, such as allergic contact dermatitis. Here, we report a case of a healthy young female, who developed greenish discoloration of nails following the removal of gel nail extensions, which need to be differentiated from Pseudomonas aeruginosa infection and other causes such as fungal infection, subungual hematoma, and malignant melanoma, as early diagnosis may help in initiating the specific treatment, hence saving time and the need for unnecessary laboratory investigations.

Bacterial and Viral Co-Infections in COVID-19 Patients: Etiology and Clinical Impact.

Mixed infections can worsen disease symptoms. This study investigated the impact of mixed infections with viral and bacterial pathogens in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the in-house multiplex PCR method, we tested 337 SARS-CoV-2 positive samples for co-infections with three bacterial and 14 other viral pathogens. Between August 2021 and May 2022, 8% of 337 SARS-CoV-2-positive patients had bacterial co-infections, 5.6% had viral co-infections, and 1.4% had triple mixed infections. The most common causes of mixed infections were Haemophilus influenzae (5.93%) and respiratory syncytial virus (RSV) (1.18%). Children < 5 years old had more frequent co-infections than adults < 65 years old (20.8% vs. 16.4%), while adults showed a more severe clinical picture with a higher C-reactive protein (CRP) level (78.1 vs.16.2 mg/L; p = 0.033), a lower oxygen saturation (SpO2) (89.5 vs. 93.2%), and a longer hospital stay (8.1 vs. 3.1 days; p = 0.025) (mean levels). The risk of a fatal outcome was 41% in unvaccinated patients (p = 0.713), which increased by 2.66% with co-infection with two pathogens (p = 0.342) and by 26% with three pathogens (p = 0.005). Additionally, 50% of intensive care unit (ICU) patients had a triple infection, compared with only 1.3% in the inpatient unit (p = 0.0029). The risk of death and/or ICU admission was 12 times higher (p = 0.042) with an additional pathogen and increased by 95% (p = 0.003) with a third concomitant pathogen. Regular multiplex testing is important for prompt treatment and targeted antibiotic use.

Assessing the Effects of Surgical Irrigation Solutions on Human Neutrophil Interactions with Nascent Staphylococcus aureus Biofilms.

Staphylococcus aureus (S. aureus) is the leading cause of surgical site infections (SSIs) and is capable of biofilm growth on implanted foreign devices. The use of surgical irrigation solutions has become a common strategy to combat bacterial contamination events that occur during surgery. Despite their antimicrobial activity, SSI rates remain consistent, suggesting that low-level contamination persists. In these cases, circulating neutrophils must traffic from the blood to contamination sites to aid in bacterial clearance. The influence of irrigation solutions on neutrophils' ability to engage with bacteria has not been explored. The effects of three commonly used irrigation solutions: Xperience (sodium lauryl sulfate), Irrisept (chlorhexidine gluconate), and Betadine® (povidone-iodine) on nascent S. aureus biofilms alone and in the presence of human neutrophils were assessed at manufactured and diluted concentrations. All three solutions, at a 10% dilution, inhibited bacterial growth as demonstrated by culture assays and confocal video microscopy of bacterial aggregate formation. The effects of 10% dilutions of each of these solutions on neutrophil membrane integrity (by flow cytometry and propidium iodide staining) and motility (by confocal video microscopy of neutrophil track length) were investigated with differing outcomes for each irrigation solution. At this concentration only Irrisept preserved neutrophil membrane integrity and motility. Together, this study examines an overlooked aspect of surgical irrigation solutions by investigating their impact on innate immunity and highlights the feasibility of formulations wherein solution effectiveness is complemented by neutrophil function to reduce risks of infection.

Nur77 protects the bladder urothelium from intracellular bacterial infection

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with a small-molecule Nur77 agonist, cytosporone B, inhibits invasion and enhances the expulsion of UPEC from human urothelial cells in vitro, and significantly reduces UPEC IBC formation and bladder infection in mice. Our findings reveal a new role for Nur77 in control of bacterial infection and suggest that pharmacologic agonism of Nur77 function may represent a promising antibiotic-sparing therapeutic approach for UTI.

Eales’ disease with secondary coats’-like reaction: a case report

BackgroundEales’ disease is an idiopathic, inflammatory condition characterized by peripheral retinal phlebitis, distal non-perfusion, and neovascularization. Coats’ disease, on the other hand, is an idiopathic, retinal vasculopathy characterized by telangiectasia and yellowish exudation. Both diseases commonly affect males. Here, we report an atypical case of unilateral Eales’ disease with co-existing, secondary Coats’-like reaction in a 25-year-old male exhibiting unilateral retinal telangiectasia accompanied by subtle macular edema, extensive peripheral vascular sheathing, and distal non-perfusion in the absence of clinically visible exudation.MethodsCase report.ResultsA 25-year-old male presented with painless blurring of vision in the right eye for two months. Best-corrected Snellen visual acuity was 3/60 in the affected eye, with relative afferent pupillary defect observed, and 6/9 contralaterally. Anterior segment examination was unremarkable. Right eye fundoscopy showed aneurysmal telangiectasia at the macula, 360 degrees perivascular sheathing and telangiectasia of peripheral retinal vessels. There was no exudation, neovascularization, tractional membranes, vitritis, retinitis, and choroiditis. Left eye fundus was unremarkable. Optical coherence tomography of the macula revealed disorganization and thinning of the inner retinal layers with minimal intraretinal fluid. Fundus fluorescein angiography showed leakage from the aneurysms but not from the sheathed vessels, and an enlarged foveolar avascular zone. A well-defined zone of non-perfusion and retinal vascular telangiectasia with shunts was observed. Blood investigations ruled out metabolic, infectious, haematological, and autoimmune causes. Carotid Doppler showed no stenosis, and CT angiography of the brain did not show any vascular abnormalities. In view that no cause was identified, a diagnosis of Eales’ disease with secondary Coats’-like reaction was made. Treatment consisted of FFA-guided laser photocoagulation to the areas of non-perfusion. Intavitreal anti-vascular endothelial growth factor injection was not done in view of poor visual prognosis. The condition and visual acuity remained stable during 18 months of follow-up.ConclusionThis report highlights an atypical case of Eales’ disease with co-existing, secondary Coats’-like reaction.

Monitoring of Pseudomonas aeruginosa mutational resistome dynamics using an enrichment panel for direct sequencing of clinical samples

Pseudomonas aeruginosa is a major cause of hospital-acquired and chronic infections, characterised by an extraordinary capacity to develop antimicrobial resistance through the selection of chromosomal mutations, leading to treatment failure. Here, we designed and tested a hybridisation-based capture system for the enrichment of genes of interest before sequencing to monitor resistant populations genomics directly from clinical samples. A panel for enrichment before sequencing of close to 200 genes related to P.aeruginosa antimicrobial resistance, multilocus sequence typing, mutability or virulence was designed, synthesised (KAPA HyperCap, Roche) and initially validated invitro using a multidrug-resistant ST175 isolate and representative isolates from major P.aeruginosa clades. Invivo testing included ventilator associated pneumonia by MDR P.aeruginosa in ICU (3-10 sequential samples from 3 patients) and chronic respiratory infection by hypermutable P.aeruginosa in cystic fibrosis (8 sequential samples from a single patient covering a 4-year period). Results from direct sequencing with the enrichment panel were compared with those of whole genome sequencing (WGS) and phenotypic profiling of 10 isolated colonies per sample. Invitro assays confirmed the selectivity of the enrichment panel and the correct identification of the vast mutational resistome of ST175, including specific mutations even when introduced in a 1:100 proportion. Invivo performance was at least equivalent to sequencing 10 colonies per sample, including the accurate identification of the sequence types and the basal and acquired mutational resistome. To note, specific resistance mutations, such as those in ampC leading to resistance to novel β-lactams, could be traced even at frequencies of 1%. Moreover, the coselection of mutator populations and antibiotic resistance mutations, predicted in theoretical and invitro studies, was evidenced invivo. This proof-of-concept study demonstrates that resistance genomics of P.aeruginosa can be analysed directly from clinical samples, determining not only a considerable reduction in turnaround time and cost from a diagnostics perspective, but also an unprecedented potency for accurate monitoring of invivo population dynamics in bacterial infections. Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.

Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice

ABSTRACT Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine’s efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.

Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model.

Tuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration. However, little is known about its role in the setting of TB infection. Here, we show that Mycobacterium tuberculosis (Mtb) infection increases CCRL2 protein expression in macrophages and in mouse lungs. To target selectively CCRL2-expressing cells in vivo, we developed a novel mouse anti-CCRL2 antibody-drug conjugate (ADC) linked with the cytotoxic drug SG3249. We tested its adjunctive therapeutic efficacy against TB when combined with the first-line regimen for drug-susceptible TB (isoniazid, rifampin, pyrazinamide, ethambutol; RHZE). The anti-CCRL2 ADC treatment potentiated RHZE efficacy in Mtb-infected mice and decreased gross lung inflammation. CCRL2 expression in lung dendritic cells and alveolar macrophages was lower in mice receiving anti-CCRL2 ADC treatment + RHZE compared to those receiving RHZE alone or the control group, although the total innate cell populations did not differ across treatment groups. Interestingly, neutrophils were completely absent in the anti-CCRL2 ADC treatment + RHZE group, unlike in the other treatment groups. IFN-γ+ and IL17-Α+ T-cell responses, which are associated with optimal TB control, were also elevated in the anti-CCRL2 ADC treatment + RHZE group. Collectively, our findings suggest that CCRL2-targeting approaches may improve TB treatment outcomes, possibly through selective killing of Mtb-infected innate immune cells.

Misuse of Antibiotics in Pediatric Patients – A Comprehensive Review .

To identify and assess the likely causes of antibiotic overuse in the Pediatric outpatient department (OPD) of a busy teaching hospital. Overuse of antibiotics has emerged as a significant global pediatric concern. Specifically, the sale of drugs without a prescription from a doctor and other circumstances may have an impact on the abuse of antibiotics. Antibiotic resistance is encouraged by the misuse of antibiotics, particularly when antibiotics are used, even when they are not the recommended course of therapy. The Centers for Disease Control and Prevention estimate that between one-third and half of all antibiotic usage in humans is unwarranted or improper. Viral pathogens are the primary cause of respiratory tract infections (RTI) in children compared to adults. Interestingly, compared to adults with RTI, very little is known regarding the usage of antibiotics in children.

Influence of a synthetic analogue of the active center of GM-CSF – peptide ZP2 on the growth and biofilm formation of gram-negative bacteria – causes of surgical infections

The aim is to analyze the nature of the effect of the synthetic analogue of the active center of GM- CSF – peptide ZP2 on the growth and biofilm formation (BPO) of gram–negative bacteria – pathogens of surgical infections. The study used 18 clinical isolates of gram-negative bacteria of different species (Klebsiella pneumoniae, Citrobacter freundii, Stenotrophamonas maltophilia) isolated from purulent wounds in patients with surgical pathology and showing pronounced resistance to many antibiotics used in clinical practice. The isolation of pure cultures of microorganisms was carried out by conventional methods; species were assessed by direct protein profiling using a MALDI TOF mass spectrometer. To study the effect of ZP2 peptide on bacterial growth and BPO, isolates were co-cultured with a solution of ZP2 peptide in meat-peptone broth (MPB) at a concentration of 5 micrograms/ml at 37°C for 24-48 hours. The effect of the ZP2 peptide was studied both on emerging biofilms and on those formed, according to the degree of binding of crystalline violet in sterile 96-well polystyrene plates. Next, Growth inhibition indices and coefficients of BPO of microorganisms were determined. It was found that the synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2 inhibited the growth of the studied bacterial strains, reducing the biomass of experimental cultures during the development of bacterial populations. At the same time, the species-specific effect of the ZP2 peptide on the ability of surgical strains of the studied bacteria to form biofilms has been shown. It was experimentally established that all the studied surgical strains of microorganisms were capable of biofilm formation, and the maximum severity of the trait was characteristic of S. maltophilia isolates. The synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2 caused a decrease in the ability to form biofilms in isolates S. maltophilia and destroyed already formed biofilms in all studied species of microorganisms. The experimental data obtained expand the range of potential clinical applications of the synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2, and its use in new medicines can be effective in combating antibiotic-resistant pathogens of surgical infections.

The Oxylipin Dependent Quorum Sensing System enhances Pseudomonas aeruginosa dissemination during burn-associated infection.

Following severe burn injury, Pseudomonas aeruginosa is the leading cause of life-threatening infection. Herein, we unveil how P. aeruginosa strategically employs host-derived oleic acid, released as consequence of burn-injury, to induce a hypervirulent phenotype via its Oxylipin Dependent Quorum Sensing system (ODS). ODS activation enhanced P. aeruginosa invasion of burned skin and promoted its dissemination to distant organs in vivo . ODS regulation of P. aeruginosa virulence involved the control of nitic oxide levels, a key signaling molecule in bacteria, through upregulation of the nitric oxide reductases NorCB. Immunization with OdsA, one of the enzymes involved in oxylipin generation, or treatment with a pharmacological inhibitor of OdsA, protected mice against lethal P. aeruginosa infection following burn-injury. Our findings reveal a new mechanism underlying P. aeruginosa hypervirulence in burn wounds and identifies OdsA as a promising target for preventing disseminated infections following burns.

Analysis of genetic requirements and nutrient availability for Staphylococcus aureus growth in cystic fibrosis sputum.

Staphylococcus aureus is a major cause of lung infections in people with cystic fibrosis (CF). This work identifies genes required for S. aureus growth in this niche, which represent potential targets for anti-Staphylococcal treatments. We show that genes involved in surviving metal starvation are required for growth in CF sputum. We also found that the primary regulator of cysteine metabolism, CymR, plays a critical role in preventing cysteine intoxication during growth in CF sputum. To support these models, we analyzed sputum from 11 individuals with CF to determine concentrations of calprotectin, nutrient metals, and low-molecular-weight thiols, which have not previously been quantified together in the same samples.

Disruption to de novo uridine biosynthesis alters β-1,3-glucan masking in Candida albicans.

The uridine derivatives UDP-glucose and UDP-N-acetylglucosamine are important for cell wall construction as they are the precursors for the synthesis of β-1,3-glucan and chitin, respectively. Previous studies have demonstrated attenuated virulence of uridine auxotrophs in mice, which has been attributed to insufficient uridine levels for growth in the host. We have discovered that uridine deprivation in the uridine auxotroph ura3ΔΔ disrupts cell wall architecture by increasing surface mannans, exposing β-1,3-glucan and chitin, and decreasing UDP-sugar levels. Cell wall architecture and UDP-sugars can be rescued with uridine supplementation. The cell wall architectural disruptions in the ura3ΔΔ mutant also impact immune activation since the mutant elicited greater TNFα secretion from RAW264.7 macrophages than wild type. To determine if cell wall defects contributed to decreased virulence in the ura3ΔΔ mutant, we used a murine model of systemic infection. Mice infected with the ura3ΔΔ mutant exhibited increased survival and reduced kidney fungal burden compared with mice infected with wild type. However, suppression of the immune response with cyclophosphamide did not rescue virulence in mice infected with the ura3ΔΔ mutant, indicating the attenuation in virulence of uridine auxotrophs can be attributed to decreased growth in the host but not increased exposure of β-1,3-glucan. Moreover, the ura3ΔΔ mutant is unable to grow on ex vivo kidney agar, which demonstrates its inability to colonize the kidneys due to poor growth. Thus, although uridine auxotrophy elicits changes to cell wall architecture that increase the exposure of immunogenic polymers, metabolic fitness costs more strongly drive the observed virulence attenuation.IMPORTANCECandida albicans is a common cause of bloodstream infections (candidemia). Treatment of these bloodstream infections is made difficult because of increasing antifungal resistance and drug toxicity. Thus, new tactics are needed for antifungal drug development, with immunotherapy being of particular interest. The cell wall of C. albicans is composed of highly immunogenic polymers, particularly β-1,3-glucan. However, β-1,3-glucan is naturally masked by an outer layer of mannoproteins, which hampers the detection of the fungus by the host immune system. Alteration in cell wall components has been shown to increase β-1,3-glucan exposure; however, it is unknown how the inability to synthesize precursors to cell wall components affects unmasking. Here, we demonstrate how cell wall architecture is altered in response to a deficit in precursors for cell wall synthesis and how uridine is a crucial component of these precursors.