Abstract Malaria is one of the most life‐threatening infectious diseases worldwide, caused by infection of humans with parasites of the genus Plasmodium . The complex life cycle of Plasmodium parasites is shared between two hosts, with infection of multiple cell types, and the parasite needs to adapt for survival and transmission through significantly different metabolic environments. Within the blood‐stage alone, parasites encounter changing levels of key nutrients, including sugars, amino acids, and lipids, due to differences in host dietary nutrition, cellular tropism, and pathogenesis. In this review, we consider the mechanisms that the most lethal of malaria parasites, Plasmodium falciparum, uses to sense nutrient levels and elicit changes in gene expression during blood‐stage infections. These changes are brought about by several metabolic intermediates and their corresponding sensor proteins. Sensing of distinct nutritional signals can drive P. falciparum to alter the key blood‐stage processes of proliferation, antigenic variation, and transmission.
Abstract Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives Dermatophytes are keratinophilic fungi that cause skin infections among animals and humans. Recently, the incidence rates of fungal infections especially due to the Trichophyton spp. are being considered as endemic in many geographical locations. The cause of recent surge of dermatophytosis due to this agent in humans is not known. It is assumed that pets may be one of the sources which are not established till now. The present study was conducted to understand the molecular heterogeneity of Trichophyton spp. of canines and felines, and their phylogenetic relationship with human isolates. Methods The samples (skin scrapings) were collected from 386 canines and 56 felines exhibiting clinical signs of ringworm during the period of 2020-2021 from the veterinary hospitals and farms in the states of Uttar Pradesh and Kerala, India. All the samples were attempted for isolation on Sabouraud's dextrose agar (with chloramphenicol and cycloheximide at 0.05 and 0.5 g/l, respectively). The antifungal susceptibility assay was performed by following the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-Ed3 for filamentous fungi (CLSI: Wayne, PA, USA, 2017). The isolates presumptively identified as Trichohypton spp. were characterized further based on PCR and sequencing of three genetic markers such as ITS, Tef1-α, and beta-tubulin genes. Phylogenetic analysis and taxonomical determination of the Trichophyton isolates were performed. Three human isolates of T. mentagrophytes were used for comparative study. Results A total of 67 (15.16%, 67/442) samples revealed the presence of fungal hyphae on direct microscopic examination. On culturing, 52 samples were found to be positive for dermatophytes. Among these, 10 isolates were presumptively identified as T. mentagrophyte spp. based on morphological and microscopic examinations. Most of the strains were sensitive to all drugs tested except fluconazole, which showed a resistance pattern for most strains. Based on sequence homology and phylogenetic inferences, the Trichophyton isolates belonged to four different species/genotypes, such as T. mentagrophytes genotype VIII (5), T. interdigitale (2), T. simmi (2), and T. quinckeanum (1). Human isolates were represented as T. mentagrophytes genotype VIII (2) and T. benhamie (1). Conclusion To conclude, the study reports for the first time the prevalence, species diversity, and antifungal resistance among Trichophyton spp. from canines in India. Even though the Trichophyton prevalence was lower in canines, the presence of T. mentagrophytes genotype VIII/T. indotineae is of great public health significance. This indicates the zoonotic sharing of strains especially T. mentagrophytes gentotype VIII in both hosts that are also considered as the recently endemic pathogenic clone in India.
Abstract The survival of pathogenic Leptospira in the host pivots on its proficiency to circumvent the immune response. These pathogens evade the complement system in serum by enticing and amassing the serum complement regulators onto their surface. ErpY-like lipoprotein, a surface-exposed protein of Leptospira spp., is conserved and exclusively present in the pathogenic spirochete. The recombinant form of this protein is comprehended to interact with multiple extracellular matrix (ECM) components and serum proteins like soluble complement regulators factor H (FH) and factor I (FI). Here, we document that the supplementation of recombinant ErpY-like protein (40 µg/mL) in the host (humans) serum augments the viability of E. coli and saprophytic L. biflexa by more than 2-fold. Pure complement regulators FH and FI, when bound to rErpY-like protein, preserve their respective cofactor and protease activity mandated to cleave the complement component C3b. The supplementation of rErpY-like protein (40 µg/mL) in serum ensued in ∼90 % reduction of membrane attack complex (C5b-9/MAC) deposition through alternate complement pathway (AP) activation. However, rErpY-like protein could moderately reduce (∼16%) MAC deposition in serum through the classical pathway (CP). In addition, the rErpY-like protein solely activated the AP, suggesting its role in the rapid consumption and depletion of the complement components. Blocking the pathogenic L. interrogans surface with anti-rErpY resulted in an increase in MAC formation on the bacterial surface, indicating a specific role of the ErpY-like lipoprotein in complement-mediated immune evasion. This study underscores the role of the ErpY-like lipoprotein of Leptospira in complement evasion.
Outbreaks of Peste des petits ruminants (PPR) viral disease in Black Bengal goats were investigated from the middle Indo-Gangetic Plains of India. Clinical profile of PPR-affected flocks was recorded from four different outbreak sites of the region. The PPR outbreak was diagnosed serologically using commercially available sandwich ELISA kit. Relatively, low mortality rate (mean 26.75%) for PPR outbreak was recorded due to the endemic status of the disease. To understand the role of oxidative stress in PPR virus pathogenesis, various oxidant and antioxidant parameters in goats infected with PPR were estimated and compared with the uninfected/healthy goats of the same flock. The measured high level of pro-oxidant malondialdehyde (MDA) obtained from lipid peroxidation along with lower levels of anti-oxidants viz. superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in PPR-affected Black Bengal goats suggests oxidative stress as one of the mechanism of pathogenesis of PPR virus. In addition, the correlation of oxidative stress due to PPR and the resulting reproductive disorders in the female goats were evaluated. The abortion in pregnant does observed during PPR outbreak was proportional to debility and oxidative stress manifested during PPR infection. The reproductive performance of recovered female goats in the period of 18 months of monitoring was significantly compromised in terms of kidding and twinning frequency. The mortality rate in kids born from PPR-recovered goats was significantly higher compared to those from health goats in the first 9 months post-recovery. From the present study, it may be concluded that together with the PPR virus, infection in goats and the resulting oxidative stress play a vital role for abortion and reduced post-reproductive performance in Black Bengal female goat.
Diabetes mellitus is a chronic disease-which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycemia). Diabetes mellitus is one of the most challenging health problems in India. The present study was investigated for isolation and characterization of antibiotic-resistant bacteria from urinary tract infection on diabetic mellitus patients. The 118 diabetic urine samples were collected and UTI bacteria using HiChrome UTI Agar was isolated. The diabetic UTI isolates were confirmed as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus saprophyticus, Proteus mirabilis and Klebsiella aerogenes based on morphological and biochemical characteristics. Our study identified that almost all the bacteria were highly sensitive to Cefoperazone/Sulbactam (75/30 mcg), Gentamicin (10 mcg), Meropenem (30 mcg), Piperacillin/Tazobactam (100/10 mcg) and Nitrofurantoin (100 mcg) antibiotics. Interestingly Klebsiella aerogenes alone was found to be more resistant to the entire antibiotics used in this study. The antibiotic resistant Klebsiella aerogenes is one of the biggest treats to human health, antibiotic resistance occurs naturally, but misuse of antibiotics in humans is accelerating the process.
Abstract Background The maintenance of Borrelia burgdorferi in its complex tick-mammalian enzootic life cycle is dependent on the organism's adaptation to its diverse niches. To this end, the RpoN-RpoS regulatory pathway in B. burgdorferi plays a central role in microbial survival and Lyme disease pathogenesis by up- or down-regulating the expression of a number of virulence-associated outer membrane lipoproteins in response to key environmental stimuli. Whereas a number of studies have reported on the expression of RpoS and its target genes, a more comprehensive understanding of when activation of the RpoN-RpoS pathway occurs, and when induction of the pathway is most relevant to specific stage(s) in the life cycle of B. burgdorferi , has been lacking. Results Herein, we examined the expression of rpoS and key lipoprotein genes regulated by RpoS, including ospC , ospA , and dbpA , throughout the entire tick-mammal infectious cycle of B. burgdorferi . Our data revealed that transcription of rpoS , ospC , and dbpA is highly induced in nymphal ticks when taking a blood meal. The RpoN-RpoS pathway remains active during the mammalian infection phase, as indicated by the sustained transcription of rpoS and dbpA in B. burgdorferi within mouse tissues following borrelial dissemination. However, dbpA transcription levels in fed larvae and intermolt larvae suggested that an additional layer of control likely is involved in the expression of the dbpBA operon. Our results also provide further evidence for the downregulation of ospA expression during mammalian infection, and the repression of ospC at later phases of mammalian infection by B. burgdorferi . Conclusion Our study demonstrates that the RpoN-RpoS regulatory pathway is initially activated during the tick transmission of B. burgdorferi to its mammalian host, and is sustained during mammalian infection.
Borrelia burgdorferi genome harbors several paralogous gene families (pgf) that can encode immunogenic proteins of unknown function. Protein–protein interaction assays using a transmission-blocking vaccine candidate, BBA52, as bait identified an interacting partner in spirochetes—a member of pgf 54, annotated as BBI39. We show that BBI39 is a surface-exposed membrane antigen that is immunogenic during spirochete infection, despite the gene being primarily transcribed in the vector with a transient expression in the host only at tick-bite sites. Immunization of rodents with BBI39, or a diverse paralog, BBI36, or their combination impaired pathogen acquisition by the vector, transmission from ticks to hosts, or induction of disease. High-titer BBI39 immunoglobulin G antibodies, which have borreliacidal properties, could be generated through routine subcutaneous or oral immunization, further highlighting use of BBI39 proteins as novel Lyme disease vaccines that can target pathogens in the host or in ticks.