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Leishmaniasis significantly affects the population of the tropics and subtropics. Clinical features and infective species of Leishmania are the primary factors driving the direction of diagnosis. The rise in incidences of atypical presentations present a challenge in patient treatment. Knowledge of unusual/rare presentations can aid in having a broader perspective for including the different aspects during the examination and thus avoid misdiagnosis. A comprehensive literature survey was performed to present the array of atypical presentations confounding clinicians which have been seen in leishmaniasis. Case reports of unusual findings based on the localizations and morphology of lesions and infective species and the predominant geographical sites over almost five decades highlight such presentations in the population. Information regarding the clinical features recorded in the patient and the chosen treatment was extracted to put forward the preferred drug regimen in such cases. This comprehensive review presents various unusual observations seen in visceral leishmaniasis, post-kala-azar dermal leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. It highlights the need to consider such features in association with differential diagnosis to facilitate proper treatment of the patient.

To strengthen malaria surveillance, field-appropriate diagnostics requiring limited technical resources are of critical significance. Loop-mediated isothermal amplification (LAMP) based malaria diagnostic assays are potential point-of-care tests with high sensitivity and specificity and have been used in low-resource settings. Plasmodium vivax–specific consensus repeat sequence (CRS)-based and Plasmodium falciparum–specific 18S rRNA primers were designed, and a two-tube LAMP assay was developed. The diagnostic performance of a closed-tube LAMP assay and Loopamp™ Malaria Detection (Pan/Pf, Pv) kit was investigated using nested PCR confirmed mono- and co-infections of P. vivax and P. falciparum positive (n = 149) and negative (n = 67) samples. The closed-tube Pv LAMP assay showed positive amplification in 40 min (limit of detection, LOD 0.7 parasites/µL) and Pf LAMP assay in 30 min (LOD 2 parasites/µL). Pv LAMP and Pf LAMP demonstrated a sensitivity and specificity of 100% (95% CI, 95.96–100% and 89.85–100%, respectively). The LoopampTM Pan/Pf Malaria Detection kit demonstrated a sensitivity and specificity of 100%, whereas LoopampTM Pv showed a sensitivity of 98.36% (95% CI, 91.28–99.71%) and specificity of 100% (95% CI, 87.54–100%). The developed two-tube LAMP assay is highly sensitive (LOD ≤ 2 parasite/µL), demonstrating comparable results with the commercial Loopamp™ Malaria Detection (Pf/pan) kit, and was superior in detecting the P. vivax co-infection that remained undetected by the Loopamp™ Pv kit. The developed indigenous two-tube Pf/Pv malaria detection can reliably be used for mass screening in resource-limited areas endemic for both P. falciparum and P. vivax malaria.

Background: The resistance to colistin and carbapenems in Klebsiella pneumoniae infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance.Methods: Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system (phoPQ and pmrAB), regulatory transmembrane protein-coding mgrB, and mobilized colistin resistance genes (mcr-1-8). Gene expression of pmrC and pmrK was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools.Results: Of 335 Klebsiella spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). K. pneumoniae isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in phoP (T151A), phoQ (del87–90, del263–264, L30Q, and A351D), pmrA (G53S), pmrB (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and mgrB (C28G) genes. The mgrB gene in three strains was disrupted by insertion sequences encoding IS1-like and IS5/IS1182 family-like transposase genes. All 11 isolates showed an elevation in the transcription level of pmrC gene. Mobilized colistin-resistance (mcr) genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes blaNDM-1-like, blaOXA-48-like, and blaCTX-M-like were detected in eight, five, and nine isolates, respectively.Conclusion: All the studied colistin- and carbapenem-resistant K. pneumoniae isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species.

Background: The resistance to colistin and carbapenems in Klebsiella pneumoniae infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance. Methods: Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system (phoPQ and pmrAB), regulatory transmembrane protein-coding mgrB, and mobilized colistin resistance genes (mcr-1-8). Gene expression of pmrC and pmrK was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools. Results: Of 335 Klebsiella spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). K. pneumoniae isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in phoP (T151A), phoQ (del87–90, del263–264, L30Q, and A351D), pmrA (G53S), pmrB (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and mgrB (C28G) genes. The mgrB gene in three strains was disrupted by insertion sequences encoding IS1-like and IS5/IS1182 family-like transposase genes. All 11 isolates showed an elevation in the transcription level of pmrC gene. Mobilized colistin-resistance (mcr) genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes blaNDM-1-like, blaOXA-48-like, and blaCTX-M-like were detected in eight, five, and nine isolates, respectively. Conclusion: All the studied colistin- and carbapenem-resistant K. pneumoniae isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species.

Introduction: The avian influenza (AI) virus causes a highly contagious disease which is common in wild and domestic birds and sporadic in humans. Mutations and genetic reassortments among the 8 negative-sense RNA segments of the viral genome alter its pathogenic potential, demanding well-targeted, active surveillance for infection control. Methods: Wild duck fecal samples were collected during the 2018 bird health annual surveillance in South Korea for tracking variations of the AI virus. One low-pathogenic avian influenza H5N3 reassortment virus (A/mallard duck/South Korea/KNU18-91/2018 [H5N3]) was isolated and genomically characterized by phylogenetic and molecular analyses in this study. Results: It was devoid of polybasic amino acids at the hemagglutinin (HA) cleavage site and exhibited a stalk region without deletion in the neuraminidase (NA) gene and NA inhibitor resistance-linked E/D627K/N and D701N marker mutations in the PB2 gene, suggesting its low-pathogenic AI. It showed a potential of a reassortment where only HA originated from the H5N3 poultry virus of China and other genes were derived from Mongolia. In phylogenetic analysis, HA was different from that of the isolate of H5N3 in Korea, 2015. In addition, this novel virus showed adaptation in Madin-Darby canine kidney cells, with 8.05 ± 0.14 log10 50% tissue culture infectious dose (TCID50) /mL at 36 h postinfection. However, it could not replicate in mice well, showing positive growth at 3 days postinfection (dpi) (2.1 ± 0.13 log10 TCID50/mL) but not at 6 dpi. Conclusions: The HA antigenic relationship of A/mallard duck/South Korea/KNU18-91/2018 (H5N3) showed differences toward one of the old low-pathogenic H5N3 viruses in Korea. These results indicated that a novel reassortment low-pathogenic avian influenza H5N3 subtype virus emerged in South Korea in 2018 via novel multiple reassortments with Eurasian viruses, rather than one of old Korean H5N3 strains.

Background Pathogenic microbes routinely keep encountering different types of stress in their environment such as high osmolarity, high temperature, pH fluctuations in host gut etc. They tend to acquire certain small molecular weight molecules, termed osmolytes, so as to handle these challenges and survive in harsh conditions. These osmolytes include some which are self-synthesized by the microorganisms, while majority of them are imbibed from the external environment via osmolyte transporters. Methods In this review, we have discussed work done on osmolytes and their transport systems, which influence upon sustenance and virulence of the pathogens under the given stress conditions. Results Osmolytes and their transport systems play vital role in efficient maintenance of cell turgidity and electrolyte levels for proper cell functioning. These molecules don't disturb normal metabolic processes within the microbial cell at all; it rather stabilizes the macromolecules, such as nucleic acids and proteins. Besides, these osmolytes also empower the microbes with the pathogenicity potential under harsh conditions such as salt, pH, temperature stress, and the efficient host immunity. Conclusion Exploring avenues with respect to osmolyte transport systems is the need of the hour especially in this time where we are facing the evolution of antibiotic resistance in pathogens. Most interestingly, a detailed study of bacterial stress responses would prove to be useful in comprehending what these pathogens face in the host microenvironment, whereby we can manipulate the pathogen survival in human gut, and hence address the menace of pathogenic resistance in humans as well as animals.

High susceptibility of wool toward bacterial growth owing to proteinous nature and moisture retention ability leads to need for antibacterial functionalization of wool to cure the resulting deterio...

Despite the vast availability of antibiotics, bacterial infections remain a leading cause of death worldwide. In an effort to enhance the armamentarium against resistant bacterial strains, 1,2,3-triazole (5a–x) and sulfonate (7a–j) analogues of natural bioactive precursors were designed and synthesized. Preliminary screening against two Gram-positive (Streptococcus pneumoniae and Enterococcus faecalis) and four Gram-negative bacterial strains (Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Escherichia coli) was performed to assess the potency of these analogues as antibacterial agents. Among all triazole analogues, 5e (derived from carvacrol) and 5u (derived from 2-hydroxy 1,4-naphthoquinone) bearing carboxylic acid functionality emerged as potent antibacterial agents against S. pneumoniae (IC50: 62.53 and 39.33 μg/mL), E. faecalis (IC50: 36.66 and 61.09 μg/mL), and E. coli (IC50: 15.28 and 22.57 μg/mL). Furthermore, 5e and 5u also demonstrated moderate efficacy against multidrug-resistant E. coli strains and were therefore selected for further biological studies. Compound 5e in combination with ciprofloxacin displayed a synergistic effect on multidrug-resistant E. coli MRA11 and MRC17 strains, whereas compound 5u was selective against E. coli MRA11 strain. Growth kinetic studies on S. pneumoniae and E. coli treated with 5e and 5u showed an extended lag phase. 5e and 5u did not show significant cytotoxicity up to 100 μg/mL concentration on human embryonic kidney (HEK293) cells. Transmission electron microscopic (TEM) analysis of bacterial cells (S. pneumoniae and E. coli) exposed to 5e and 5u clearly showed morphological changes and damaged cell walls. Moreover, these compounds also significantly inhibited biofilm formation in S. pneumoniae and E. coli strains, which was visualized by scanning electron microscopic (SEM) analysis. Treatment of larvae of Galleria mellonella (an in vivo model for antimicrobial studies) with 5e and 5u did not cause an alteration in the hemocyte density, thereby indicating lack of an immune response, and were nontoxic up to a concentration of 2.5 mg/mL.

Nanoparticles (NPs) have gained importance in technological advances owing to their user friendly enhanced and efficient physical, chemical, and biological characteristics compared to their bulk counterparts. Biological synthesis of NPs by using a microorganism, enzymes, or plant extracts offers a greener and eco-friendly approach besides many advantages over physical or chemical approaches. This study reports the biosynthesis of silver nanoparticles (AgNPs) using Nostoc muscorum NCCU 442 aqueous extract as the reducing and capping agent for AgNPs synthesis. The synthesized nanoparticles were characterized by UV‐VIS spectrum, SEM, EDS, TEM, AFM, DLS and XRD. Results showed distinguishing polycrystalline nature of synthesized AgNPs with surface plasmon significant band in the size range of 6‐45nm with average 30 size nm. FT-IR study revealed the role of secondary metabolites present in aqueous extract for the synthesis of AgNPs. Biological activities of purified AgNPs as antioxidant and antibacterial potential showed the highest antibacterial activity against Staphylococcus aureus MTCC 902.

A series of diketo esters and their pertinent bioisosteres were designed and synthesized as potent antibacterial agents by targeting methionine amino peptidases (MetAPs). In the biochemical assay against purified MetAPs from Streptococcus pneumoniae (SpMetAP1a), Mycobacterium tuberculosis (MtMetAP1c), Enterococcus faecalis (EfMetAP1a) and human (HsMetAP1b), compounds 3a, 4a and 5a showed more than 85% inhibition of all the tested MetAPs at 100 μM concentration. Compounds 4a and 5a also exhibited antibacterial potential with MIC values 62.5 μg/mL (S. pneumoniae), 31.25 μg/mL (E. faecalis), 62.5 μg/mL (Escherichia coli) and 62.5 μg/mL (S. pneumoniae), 62.5 μg/mL (E. coli), respectively. Moreover, 5a also significantly inhibited the growth of multidrug resistant E. coli strains at 512 μg/mL conc., while showing no cytotoxic effect towards healthy CHO cells and thus being selected. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 5a. TEM analysis also displayed vital damage to bacterial cells by 5a at MIC conc. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 5a as visualized by SEM micrographs. Interestingly, 5a did not cause an alteration in the hemocyte density in Galleria mellonella larvae which is considered in vivo model for antimicrobial studies and was non-toxic up to a conc. of 2.5 mg/mL.

Growing interests in the development of advanced functional materials from renewable resources due to the depleting petroleum resources, increasing costs, and associated hazards reflect global requirement for increased sustainability. Cardanol [Col] is an agro by-product of the cashew nut industry. It is cost effective, nontoxic, biodegradable and an abundantly available renewable resource. In the present study, we report the development of nanostructured coordination polymer [CP] self-standing transparent films from Col (as an organic linker or bridging-ligand) and Mn(II) ‘d5’ and Co(II) ‘d7’ divalent metal ions (as metal nodes) by a solid-state in situ method. The resulting CP films showed nanoporous morphology, amorphous behaviour, good thermal stability up to 260–300 °C, moderate antibacterial activity against Staphylococcus aureus (MTCC 902), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (MTCC 2453) and also good anti-biofilm activity.

Plants being sessile are shaped by evolution to adapt themselves and tolerate various stresses, be it salinity stress, drought, high/low temperature in nature. They have evolved with every alternate strategy to tackle serious abiotic stresses through considerable degree of developmental plasticity, including adaptation via cascades of molecular networks. Understanding the mechanism of genes responsible for plant adaptation to environment will help in predicting the scenarios, expanding the genetic aspect of abiotic stress-regulating genes to protect and extrapolate the level of tolerance or vulnerability conferred in natural ecosystems. Complementing the agronomic need for greater tolerance to abiotic stress, studying plant abiotic stress response can help in gaining insight into plant biology that can be practically applied to unlock the secrets in order to improve plant productivity to feed the ever increasing population of human beings.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau) are useful core biomarkers in the cerebrospinal fluid (CSF) of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB) in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.

Efficient utilization of renewable feedstocks has been considered pivotal in sustainable development, controlling global warming, and as an alternative to petrochemical precursors. Here, we have presented a facile one-pot synthesis method for the fabrication of bacterial resistant, free-standing polymeric films and coatings by utilizing agro-waste based precursor material. The conversion of cashew nut shell liquid (CNSL) into a value-added product for this application was achieved through coordination of methylolated-CNSL and Mg (II) ions (Mg(II)CNSL). The resulting metal-organic framework (MOF) was then cured by following a greener approach with zero toxic/residue production through reacting Mg(II)CNSL with aliphatic amine [Mg(II)CNSL-FA]. The formulation mechanism of nanostructured Mg(II)CNSL-FA via the ring-opening reaction of benzoxazine, its polymerization with hydroxyl groups in CNSL, and coordination of Mg(II) ions were elucidated by FTIR, ATR, XRD, SEM/TEM, and DSC studies. The performance (flexibility, swelling behaviour, and water contact angle values), morphology, and thermal stability of Mg(II)CNSL-FA films were also compared (virgin ligand, CNSL-FA). The potential application of the film as an antibacterial material has been further tested against various bacterial strains (E.coli, P. aeruginosa, S. aureus, and B. subtilis). Overall, the research work is expected to broaden the utilization of CNSL, an agro-waste via cleaner production of flexible, free-standing, metal ions coordinated antibacterial film with possible application in surface coatings, adsorption, and water purification.

Metals being recalcitrant to biodegradation process pose a persistent threat to human health and environment. In view of increase in discharge along with improper management of persistent metal pollutants, it is imperative to develop cost-effective and efficient methods for their remediation. As contamination of soil and water has threatened the well being of humans and natural environment, microorganisms play crucial role in combating the widespread pollution of global environment. Clusters of genes coding for catabolic transformation facilitate their detoxification from the environment. Development of effective tools to facilitate environmental cleanup of metal pollutants beyond genetic confines of natural host has resulted in the expressional enhancement of promiscuous enzymes, involved in the transformation of metal compounds. A thorough understanding of microbes that express heterologous proteins for metal transformation would result in economic production and as such its application in bioremediatio...

Escalating burden of antibiotic resistance that has reached new heights present a grave concern to mankind. As the problem is no longer confined to clinics, we hereby report identification of a pandrug resistant Escherichia coli isolate from heavily polluted Delhi stretch of river Yamuna, India. E. coli MRC11 was found sensitive only to tobramycin against 21 antibiotics tested, with minimum inhibitory concentration values >256 µg/mL for amoxicillin, carbenicillin, aztreonam, ceftazidime and cefotaxime. Addition of certain heavy metals at higher concentrations were ineffective in increasing susceptibility of E. coli MRC11 to antibiotics. Withstanding sub-optimal concentration of cefotaxime (10 µg/mL) and mercuric chloride (2 µg/mL), and also resistance to their combinatorial use, indicates better adaptability in heavily polluted environment through clustering and expression of resistance genes. Interestingly, E. coli MRC11 harbours two different variants of blaTEM (blaTEM-116 and blaTEM-1 with and without extended-spectrum activity, respectively), in addition to mer operon (merB, merP and merT) genes. Studies employing conjugation, confirmed localization of blaTEM-116, merP and merT genes on the conjugative plasmid. Understanding potentialities of such isolates will help in determining risk factors attributing pandrug resistance and strengthening strategic development of new and effective antimicrobial agents.

Plants infected by a wide range of viruses often cause important agronomic and economic losses worldwide. Detection of plant viruses is becoming more challenging as globalisation of trade, particularly the ornamental plants, and the potential effects of climate change facilitate movement of viruses and their vectors, thereby transforming the diagnostic landscape. Under such circumstances, detection of viruses at premature stages of infection by use of rapid, sensitive and accurate detection methods seems crucial to ensure safe and sustainable agriculture and as such reduces economic losses. For proper identification, detection technique needs to be rapid, most accurate and inexpensive, as it forms the key step in developing appropriate practical solutions to manage plant virus diseases that pose continuous threats to the viability of certain horticultural and agricultural industries. This review is concerned with the advancement in techniques in the diagnosis of viruses in plants.

Item does not contain fulltext Mercury pollution is a major environmental problem that arises as a result of natural processes as well as from anthropogenic sources. In response to toxic mercury compounds, microbes have developed astonishing array of resistance systems to detoxify them. To address this challenge, this study was aimed in screening bacterial isolates for their tolerance against varied concentrations of phenylmercuric acetate. Mercury transformation by bacteria being sensitive to factors such as available carbon source, etc. that affect mer-mediated transformation, screened mercury tolerant bacteria were also studied for their tolerance to different antimicrobials and carbon sources, followed by identification using biochemical as well as 16S rRNA approach. Following identification, gene encoding organomercurial lyase catalyzing protonolytic cleavage of C-Hg bond of organic mercury was amplified using gene specific primers, cloned in pGEMT((R)) easy vector and sequenced. Microbe-based approach using organomercurial lyase encoded by merB gene being potentially economic, provides foundation to facilitate genetic manipulation of this environmentally important enzyme to remove high concentrations of obstinate mercury using holistic, multifaceted approach for use in bioremediation through generation of transgenics or as catalyst for use in bioreactors.

Control of plant diseases has always remained a challenge as diseases affecting plant health are a major and chronic threat not only to food production, but also to ecosystem stability worldwide. As agricultural production intensified over the past three decades, producers became dependent on agrochemicals as a relatively reliable method of crop protection. However, growing concerns regarding continued use of agrochemicals, posing adverse effects on human health besides posing the threat of environmental deterioration, has driven search for novel environment friendly methods to control plant diseases that in turn can contribute to the goal of sustainability in agriculture. Mitigation of plant diseases by naturally inhabiting antagonistic micro-organisms such as plant growth-promoting rhizobacteria has gained much importance as biocontrol agents seem to be the best possible measures for saving plants from phytopathogenic organisms without causing any harmful effect to mankind as well as to the environment....