The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed enhanced membrane permeabilization and depolarization activity against intact S. aureus. Scanning electron microscopy confirmed a membrane disruptive mode of action for KKK-MSH. Overall, increasing the cationic charge improved the staphylocidal activity of α-MSH without compromising its cell selectivity. The present study would help in designing more effective α-MSH-based peptides to combat clinically relevant staphylococcal infections.

We explored medical student's views and perceptions of a series of debates conducted during problem-based learning (PBL) practiced as a part of the Spiral curriculum at the Imam Abdulrahman Bin Faisal University, Saudi Arabia. A series of debates were employed during PBL sessions for second-year female medical students, over the period 2014-2016. Each cohort of students was randomly split into 10 small PBL groups and exposed to weekly PBL activity. Within each group, the students were divided into a proposition half and an opposition half. Students were given 1 wk for debate preparation. The students' responses were recorded on a formulated questionnaire. Descriptive statistics were used to analyze quantitative data, and results are presented as percentages. The usefulness of debate in alleviating potential difficulties in communicating with patients was agreed to by 69% ( = 126) of participants. That these sessions evoked critical thinking among students was reported by 78% ( = 142). This series of debates helped 61% ( = 111) of students to learn effectively about controversial issues. Seventy-one percent ( = 130) considered that debate promoted argument generation and interpretation skills. Enhanced ability to analyze and research evidence was reported by 59% ( = 108) of students. One hundred and thirteen students (62%) agreed that debate helped them to improve clinical decision-making, and 75% of students agreed that debates encouraged tolerance toward diverse viewpoints/convincing strategies. The majority of our medical students found debating enhanced analytic decision-making, communication, and critical thinking skills.

The rapid urbanization and industrial development have resulted in water contamination and water quality deterioration at an alarming rate, deeming its quick, inexpensive and accurate detection imperative. Conventional methods to measure water quality are lengthy, expensive and inefficient, including the manual analysis process carried out in a laboratory. The research work in this paper focuses on the problem from various perspectives, including the traditional methods of determining water quality to gain insight into the problem and the analysis of state-of-the-art technologies, including Internet of Things (IoT) and machine learning techniques to address water quality. After analyzing the currently available solutions, this paper proposes an IoT-based low-cost system employing machine learning techniques to monitor water quality in real time, analyze water quality trends and detect anomalous events such as intentional contamination of water.

No abstract

Escalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1.4-22.7 μg/mL). Mechanistically, the active peptidomimetics dissipated membrane potential and caused massive permeabilization on MRSA concomitant with loss of viability. Against stationary phase MRSA under nutrient-depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log reduction in viability upon 24 h incubation while both S-7 (at 226 μg/mL) and S-8 (at 28 μg/mL) also destroyed 48 h mature MRSA biofilm causing significant decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8 maintained efficacy against MRSA in presence of serum/plasma while exhibiting no increase in MIC over 17 serial passages at sub-MIC concentrations implying resistance development to be less likely. Therefore, we envisage that the current template warrants further optimization towards the development of cell selective peptidomimetics for the treatment of device associated MRSA infections.Pan-resistant microbial pathogens refractory to current clinical antibiotics are spreading at an unprecedented rate 1 . Among human pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is a high priority clinical threat 2 . Multidrug resistance and expression of multiple virulence factors have further exacerbated the clinical severity of MRSA infections in clinics as well as community settings 3 . Moreover, with the growing use of medical implants in clinics, almost 65-80% MRSA infections in vivo have been reported to be associated with biofilm formation. Biofilms are large agglomerations of bacterial cells encased in a self-produced matrix that exhibit substantial recalcitrance to antibiotic treatment 4 (10 to 1000-fold more antibiotic concentration is required to eradicate biofilms). The recalcitrance of biofilms is multifactorial involving high localized inoculum, poor penetration of antibiotics to the core of biofilms, slow-growing nutrient-depleted bacterial populations and presence of persister cells 5,6 . Additionally, matrix formation allows the creation of a microenvironment which promotes resistance and tolerance development in microbes along with providing protection from host immune surveillance 7 . Therefore, a lot of efforts are being directed towards optimization of novel molecules/strategies to eradicate clinically relevant biofilms [8][9][10] . Recently, the consensus is emerging that unlike single target capturing antibiotics; membrane disruptive, dual target...