Interkingdom polymicrobial biofilms formed by Gram-positive Staphylococcus aureus and Candida albicans pose serious threats of chronic systemic infections due to the absence of any common therapeutic target for their elimination. Herein, we present the structure-activity relationship (SAR) of membrane-targeting cholic acid-peptide conjugates (CAPs) against Gram-positive bacterial and fungal strains. Structure-activity investigations validated by mechanistic studies revealed that valine-glycine dipeptide-derived CAP 3 was the most effective broad-spectrum antimicrobial against S. aureus and C. albicans. CAP 3 was able to degrade the preformed single-species and polymicrobial biofilms formed by S. aureus and C. albicans, and CAP 3-coated materials prevented the formation of biofilms. Murine wound and catheter infection models further confirmed the equally potent bactericidal and fungicidal effect of CAP 3 against bacterial, fungal, and polymicrobial infections. Taken together, these results demonstrate that CAPs, as potential broad-spectrum antimicrobials, can effectively clear the frequently encountered polymicrobial infections and can be fine-tuned further for future applications.
A field experiment was conducted to evaluate the influence of organic farming practices on soil health and crop performance of Soybean (Glycine max). The crop cultivar JS-335 of soybean was grown with 30:26.2:16.6 kg ha -1 (NPK) recommended dose of fertilizers under three management practices viz., organic, chemical and integrated (50:50) in randomized block design, replicated three times. Soil organic carbon, available N, P and K, microbial enzymatic activities, total biomass, seed yield and harvest index (HI) were analyzed during the study. It was observed that soil organic carbon (11.3 g kg ) and soil enzyme activities viz., dehydrogenase (DHA) (98.20 µ grams TPF/g soil/24 h) and alkaline phosphatase (178.2 µ grams p-nitro phenol/g soil/h) were found significantly higher in the plot managed organically while available K (320.1 mg kg ) of soybean was found highest in organic farming practices followed by integrated and chemical practices. Very poor microbial activities were observed in chemically managed plots. Thus, the study demonstrated that the organic farming practice improved soil health and performance of soybean crop.
Inappropriate and uncontrolled use of antibiotics results in the emergence of antibiotic resistance, thereby threatening the present clinical regimens to treat infectious diseases. Therefore, new antimicrobial agents that can prevent bacteria from developing drug resistance are urgently needed. Selective disruption of bacterial membranes is the most effective strategy for combating microbial infections as accumulation of genetic mutations will not allow for the emergence of drug resistance against these antimicrobials. In this work, we tested cholic acid (CA) derived amphiphiles tethered with different alkyl chains for their ability to combat Gram-positive bacterial infections. In-depth biophysical and biomolecular simulation studies suggested that the amphiphile with a hexyl chain (6) executes more effective interactions with Gram-positive bacterial membranes as compared to other hydrophobic counterparts. Amphiphile 6 is effective against multidrug resistant Gram-positive bacterial strains as well and does not allow the adherence of S. aureus on amphiphile 6 coated catheters implanted in mice. Further, treatment of wound infections with amphiphile 6 clears the bacterial infections. Therefore, the current study presents strategic guidelines in design and development of CA-derived membrane-targeting antimicrobials for Gram-positive bacterial infections.
HIGHLIGHTS• GM crops may impact nutrient cycling in the rhizosphere soil.• GM crops do not adversely influence soil microbiological processes.• Clay-humus complexes can protect Cry toxin in soils.• Risk of gene transfer from GM crops to non-target organisms is minimal.• Insufficient long-term experimental data restricts understanding of GM crop impacts.
Majority of global neonatal deaths is due to sepsis. A vast portion of these deaths occurs in developing countries due to inaccessibility of hospitals or lack of resources. Blood culture is the test to confirm sepsis, but it requires the presence of laboratory and is time-consuming. Therefore, we require simple, easy to use methods to predict sepsis in homes. Majority of the available prediction models need invasive parameters and hence become useless in the rural areas of developing countries where laboratory facilities do not exist. Non-invasive prediction models overcome these challenges to predict neonatal sepsis in places where there is a scarcity of laboratories. The aim and objective of this study are as follows: (i) to develop a practical, non-invasive prediction-model for neonatal sepsis which can be used in the rural areas of developing countries and to validate its performance. (ii) To compare the prognostic performance of the non-invasive prediction model with invasive prediction model and (iii) to create a prototype of the hardware which calculates the probability of the sepsis in neonates and sends the real-time data to the cloud. For this retrospective analysis, we extracted the data of 1446 neonates from Medical Information Mart for Intensive care III (MIMIC) database. Using stepwise logistic regression analysis, we developed and validated two prediction models. These two models were named as model NI and model O. Model O contains invasive as well as non-invasive parameters whereas model NI contains only non-invasive parameters. Model NI performed equally well in comparison to Model O despite using different predictors. The area under ROC curves for model NI and model O were 0.879 (95% CI: 0.857 to 0.899) and 0.861 (95% CI: 0.838 to 0.881) respectively. Both models were statistically significant with [Formula: see text]-value[Formula: see text].
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