Induction Of Resistance Research Articles

Macrolide-Lincosamide Resistance and Virulence Genes in Staphylococcus aureus Isolated from Clinical Specimens in Ardabil, Iran.

Staphylococcus aureus causes various hospital- and community-acquired infections. This study aimed to investigate the phenotypic and genotypic characteristics of erythromycin and inducible clindamycin resistance, virulence gene profiles, and spa types of S. aureus isolates collected from patients in Ardabil Province, Iran. A total of 118 clinical S. aureus isolates, including 50 (42.4%) methicillin-resistant S. aureus (MRSA) and 68 (57.6%) methicillin-susceptible S. aureus (MSSA) strains, were investigated. Resistance patterns were determined by the disk diffusion method and minimum inhibitory concentration (MIC) test. Inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance was detected using D-test method. The polymerase chain reaction (PCR) was used to identify the virulence and resistance-encoding genes. Additionally, the spa types of the isolates were determined using the PCR, followed by sequencing. In total, 49.1% (58/118) and 44% (52/118) of the isolates were resistant to erythromycin and clindamycin, respectively. Overall, 13.5% (16/118) of the isolates showed the iMLSB resistance phenotype. The ermC gene (72.4% [42]) was the most frequent erythromycin resistance-encoding gene, followed by ermA (60.3% [35]), ermB (60.3% [35]), ermTR (51.7% [30]), and msrA (15.5% [9]) genes among erythromycin-resistant isolates. The virulence genes hla, hld, sea, LukS PV, tst, seb, sed, eta, sec, and etb were detected in 93.2%, 74.5%, 70.3%, 32.2%, 29.6%, 17%, 8.5%, 8.5%, 5.9%, and 4.2% of the isolates, respectively. Ten different spa types were identified for 58 erythromycin-resistant S. aureus strains, of which t030 and t078 types were the most common types. A high frequency of macrolide- and lincosamide-resistant S. aureus isolates with different genetic backgrounds of resistance and virulence may be found in patients in Ardabil Province, Iran.

Yokenella regensburgei urinary tract infection in an immunocompetent patient: a case report

Yokenella regensburgei , belonging to the order Enterobacterales , is a rare and emerging human pathogen reported to cause both superficial and invasive infections. The 13 case reports in the literature worldwide highlight blood, bone and wound infections. To our knowledge this is the first case description of Y. regensburgei causing a urinary tract infection in a 69-year-old immunocompetent patient which was isolated in two separate specimens and identified using matrix-assisted laser desorption ionization time-of-flight MS. It was found to be susceptible to most antimicrobials but resistant to penicillin, amoxicillin-clavulanate, cefoxitin and colistin. Inducible chromosomal ampC resistance was demonstrated on disc approximation testing, and blaYOC-1 class C beta-lactamase, beta lactamase superfamily and MBL fold metallo-hydrolase genes were found on whole genome sequencing.

Microbial Filtrates Improved Growth Parameters of In vitro PVX Infected Potato Plantlets

This study focuses on utilizing the phenomenon of systemic acquired resistance (SAR) to control plant viruses and increased growth in vitro. The study demonstrated the induction of SAR in potato plantlets against Potato Virus X by using bacterial culture filtrates invitro. These biotic inducers included Pseudomonas spp. and Bacillus spp. The study observed the occurrence of induced resistance and enhanced growth in potato plantlets treated with culture filtrates containing these microorganisms. This was evident through a reduction in PVX infection, disease severity and associated biochemical changes (such as elevated levels of endogenous salicylic acid, protein content, chlorophyll content, peroxidase and polyphenol oxidase activities), as well as improvements in growth parameters.

Study the Antibacterial Mechanism of Diclofenac and its Activity Alone or Combined with Ciprofloxacin in Treating Urinary Tract Infection

This study aimed to compare the effects of diclofenac, ciprofloxacin and their combination groups on urine tract infection (U.T.I.s) caused by resistance E coli 0157 H7 in vitro and in vivo. Two hundred urine samples were collected from adult women patients suffering from U.T.I.s from February 2022 to July 2022. The urine specimen was cultured on the blood agar and then incubated at 37°C for (1-2) days; MacConkey agar is the media used for determining the biochemistry results, and identification by Rapidchek test which was performed on typical colonies from the selective plate. The M.I.C effect of Diclofenac began at (25600µg/ml) against resistance E coli 0157H7 while M.I.C of ciprofloxacin it was at (0.96mg/ml), but M.I.C of a combination between (diclofenacn+ciprofloxacin) it was at (400+0.48) mg/ml. Resistance induction assay,with the ciprofloxacin has increased four times, while with the diclofenac has doubled, whilst the combination between (diclofenacn+ciprofloxacin) has no changed after 21 days, according to M.I.C.in the time-kill assay, it was proved that the ciprofloxacin and the combination between (diclofenacn+ciprofloxacin) works after 6 hours, compared to the diclofenac, which started to reduce bacterial counting after 40. After that, the examination was carried out by scanning electronic microscope (S.E.M.) to exam the mechanics of diclofenac,work which was found that it was works as anti-biofilm In this study, forty-eighth (48) rabbits were used and divided into six groups as follow positive control (P.C.), negative control (N.C.), diclofenac (D.C.) in 1mg/kg group, ciprofloxacin (C.I.P.)in7mg/kg group, combination (ciprofloxacin 3.5 mg/kg+diclofenac1mg/kg)COM1 group and combination (ciprofloxacin 1.75 mg/kg+diclofenac1mg/kg) com2 All animals (injected with 0.1 ml in CFU E coli 0157 H7 by urinary catheterization route excepting negative control all group excepting negative control resulted in a significant increase in pus cell, epithelium cell concentration in the urine after three days E coli 0157 H7 infection comparison with negative control while in all experimental period after (14 days) showed no significant (P < 0.05) between positive control (P.C.) and diclofenac treated groups but combination COM1 group and com2 decrease significantly (P< 0.05) after (seven and fourteen) days comparison with positive control. diclofenac can be combined with antibiotics as an anti-virulence agent, enhancing the immune system's ability to eradicate infection

Induction of systemic resistance in Solanum lycopersicum and Capsicum annum seedlings against Fusarium wilt by Streptomyces bioformulations.

Plant diseases induced by various phytopathogens pose a significant threat to contemporary agricultural systems around the world. In modern agriculture, the use of pesticides is still a valuable and effective method to control plant diseases. However, agrochemicals are becoming less popular because of the accretion of toxic compounds perilous and potentially hazardous to humans and the environment. Taking into consideration these aspects, the present study was conducted to explore the biocontrol potential of an endophyticStreptomyces sp. SP5 bioformulations against Fusarium wilt. Three bioformulations were prepared using cell biomass and different carriers, i.e., B1 (talc-kaolin), B2 (MgSO4/glycerol/Na-alginate/talc/Ca-lignosulfonate), and B3 (calcium carbonate/CMC/talc). Apart from antagonistic action against Fusarium wilt, the influence of bioformulations on plant growth and systemic resistance was investigated by analyzing morphological parameters (root length, shoot length, root weight, shoot weight), biochemical parameters (photosynthetic pigments, non-enzymatic antioxidants), and induction of antioxidative enzymes, e.g., catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and superoxide dismutase (SOD), in S. lycopersicum and C. annum seedlings. The results revealed that Streptomyces bioformulations effectively controlled Fusarium wilt in S. lycopersicum and C. annum (82.6-83.4% and 81.8-100%, respectively). Besides reducing disease prevalence, bioformulations significantly increased all the morphological parameters and increased the activity of antioxidative enzymes, i.e., CAT, APX, GPX, and SOD, in plants. The current findings display that bioformulations can be utilized as environment-friendly biocontrol agents against Fusarium wilt and also as plant growth promoters.

Recent advances in PGPR-mediated resilience toward interactive effects of drought and salt stress in plants.

The present crisis at hand revolves around the need to enhance plant resilience to various environmental stresses, including abiotic and biotic stresses, to ensure sustainable agriculture and mitigate the impact of climate change on crop production. One such promising approach is the utilization of plant growth-promoting rhizobacteria (PGPR) to mediate plant resilience to these stresses. Plants are constantly exposed to various stress factors, such as drought, salinity, pathogens, and nutrient deficiencies, which can significantly reduce crop yield and quality. The PGPR are beneficial microbes that reside in the rhizosphere of plants and have been shown to positively influence plant growth and stress tolerance through various mechanisms, including nutrient solubilization, phytohormone production, and induction of systemic resistance. The review comprehensively examines the various mechanisms through which PGPR promotes plant resilience, including nutrient acquisition, hormonal regulation, and defense induction, focusing on recent research findings. The advancements made in the field of PGPR-mediated resilience through multi-omics approaches (viz., genomics, transcriptomics, proteomics, and metabolomics) to unravel the intricate interactions between PGPR and plants have been discussed including their molecular pathways involved in stress tolerance. Besides, the review also emphasizes the importance of continued research and implementation of PGPR-based strategies to address the pressing challenges facing global food security including commercialization of PGPR-based bio-formulations for sustainable agricultural.

Plant Stomata: An Unrealized Possibility in Plant Defense against Invading Pathogens and Stress Tolerance.

Stomata are crucial structures in plants that play a primary role in the infection process during a pathogen's attack, as they act as points of access for invading pathogens to enter host tissues. Recent evidence has revealed that stomata are integral to the plant defense system and can actively impede invading pathogens by triggering plant defense responses. Stomata interact with diverse pathogen virulence factors, granting them the capacity to influence plant susceptibility and resistance. Moreover, recent studies focusing on the environmental and microbial regulation of stomatal closure and opening have shed light on the epidemiology of bacterial diseases in plants. Bacteria and fungi can induce stomatal closure using pathogen-associated molecular patterns (PAMPs), effectively preventing entry through these openings and positioning stomata as a critical component of the plant's innate immune system; however, despite this defense mechanism, some microorganisms have evolved strategies to overcome stomatal protection. Interestingly, recent research supports the hypothesis that stomatal closure caused by PAMPs may function as a more robust barrier against pathogen infection than previously believed. On the other hand, plant stomatal closure is also regulated by factors such as abscisic acid and Ca2+-permeable channels, which will also be discussed in this review. Therefore, this review aims to discuss various roles of stomata during biotic and abiotic stress, such as insects and water stress, and with specific context to pathogens and their strategies for evading stomatal defense, subverting plant resistance, and overcoming challenges faced by infectious propagules. These pathogens must navigate specific plant tissues and counteract various constitutive and inducible resistance mechanisms, making the role of stomata in plant defense an essential area of study.

Microbial exopolysaccharide EPS66A inducing walnut (Juglans regia) resistance to bacterial blight

Bacterial blight caused by Xanthomonas arboricola pv. juglandis is a major obstacle to walnut production. EPS66A, derived from Streptomyces sp. strain HL-66, has various beneficial properties, including broad-spectrum microbe inhibition and plant disease resistance induction. To understand the effects of Xaj and EPS66A on walnut, a comprehensive analysis of the metabolome and transcriptome was conducted. While EPS66A did not directly inhibit Xaj on agar media, applying it at 200 μg/mL, 24 h after Xaj inoculation on walnut leaves, significantly reduced bacterial blight in a greenhouse. Additionally, EPS66A increased phenolic and flavonoid concentrations and enhanced enzymatic activities associated with resistance, such as catalase, superoxide dismutase, peroxidase, and phenylalanine ammonia lyase. Differential expression of eleven metabolites and fourteen genes related to flavonoid biosynthesis pathway was observed. Consequently, EPS66A application induced systemic resistance in walnuts, effectively preventing Xaj infection. This study provides insights into the flavonoid biosynthesis mechanism underlying EPS66A-induced resistance in walnuts.

Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection

BackgroundType I interferons (IFN-I) are fundamental in controlling viral infections but fatal interferonopathy is restricted in the immune-privileged central nervous system (CNS). In contrast to the well-established role of Interferon Regulatory Factor 7 (IRF7) in the regulation of IFN-I response in the periphery, little is known about the specific function in the CNS.MethodsTo investigate the role for IRF7 in antiviral response during neurotropic virus infection, mice deficient for IRF3 and IRF7 were infected systemically with Langat virus (LGTV). Viral burden and IFN-I response was analyzed in the periphery and the CNS by focus formation assay, RT-PCR, immunohistochemistry and in vivo imaging. Microglia and infiltration of CNS-infiltration of immune cells were characterized by flow cytometry.ResultsHere, we demonstrate that during infection with the neurotropic Langat virus (LGTV), an attenuated member of the tick-borne encephalitis virus (TBEV) subgroup, neurons do not rely on IRF7 for cell-intrinsic antiviral resistance and IFN-I induction. An increased viral replication in IRF7-deficient mice suggests an indirect antiviral mechanism. Astrocytes rely on IRF7 to establish a cell-autonomous antiviral response. Notably, the loss of IRF7 particularly in astrocytes resulted in a high IFN-I production. Sustained production of IFN-I in astrocytes is independent of an IRF7-mediated positive feedback loop.ConclusionIFN-I induction in the CNS is profoundly regulated in a cell type-specific fashion.

Application of a Chitosan-Cinnamon Essential Oil Composite Coating in Inhibiting Postharvest Apple Diseases.

The purpose of this study was to explore the film-forming properties of cinnamon essential oil (CEO) and chitosan (CS) and the effect of their composite coating on postharvest apple diseases. The results demonstrated that the composite coating exhibits favorable film-forming properties at CEO concentrations below 4% (v/v). The effectiveness of the composite coating in disease control can be attributed to two factors: the direct inhibitory activity of CEO against pathogens in vitro and the induced resistance triggered by CS on the fruits. Importantly, the incorporation of CEO did not interfere with the induction of resistance by CS in harvested apples. However, it is noteworthy that the inhibitory effect of the CS-CEO composite coating on apple diseases diminished over time. Therefore, a key aspect of enhancing the preservation ability of fruits is improving the controlled release properties of CEO within CS coatings. This will enable a sustained and prolonged antimicrobial effect, thereby bolstering the fruit preservation capabilities of the composite coatings.

Immunity to Cryptosporidium: insights into principles of enteric responses to infection.

Cryptosporidium parasites replicate within intestinal epithelial cells and are an important cause of diarrhoeal disease in young children and in patients with primary and acquired defects in T cell function. This Review of immune-mediated control of Cryptosporidium highlights advances in understanding how intestinal epithelial cells detect this infection, the induction of innate resistance and the processes required for activation of T cell responses that promote parasite control. The development of a genetic tool set to modify Cryptosporidium combined with tractable mouse models provide new opportunities to understand the principles that govern the interface between intestinal epithelial cells and the immune system that mediate resistance to enteric pathogens.

Molecular characterization and differential effects of levofloxacin and ciprofloxacin on the potential for developing quinolone resistance among clinical Pseudomonas aeruginosa isolates.

Fluoroquinolones are some of the most used antimicrobial agents for the treatment of Pseudomonas aeruginosa. This study aimed at exploring the differential activity of ciprofloxacin and levofloxacin on the selection of resistance among P. aeruginosa isolates at our medical center. 233 P. aeruginosa clinical isolates were included in this study. Antimicrobial susceptibility testing (AST) was done using disk diffusion and broth microdilution assays. Random Amplification of Polymorphic DNA (RAPD) was done to determine the genetic relatedness between the isolates. Induction of resistance against ciprofloxacin and levofloxacin was done on 19 isolates. Fitness cost assay was done on the 38 induced mutants and their parental isolates. Finally, whole genome sequencing was done on 16 induced mutants and their 8 parental isolates. AST results showed that aztreonam had the highest non-susceptibility. RAPD results identified 18 clusters. The 19 P. aeruginosa isolates that were induced against ciprofloxacin and levofloxacin yielded MICs ranging between 16 and 256 μg/mL. Levofloxacin required fewer passages in 10 isolates and the same number of passages in 9 isolates as compared to ciprofloxacin to reach their breakpoints. Fitness cost results showed that 12 and 10 induced mutants against ciprofloxacin and levofloxacin, respectively, had higher fitness cost when compared to their parental isolates. Whole genome sequencing results showed that resistance to ciprofloxacin and levofloxacin in sequenced mutants were mainly associated with alterations in gyrA, gyrB and parC genes. Understanding resistance patterns and risk factors associated with infections is crucial to decrease the emerging threat of antimicrobial resistance.

Distribution of MecA and Erm Genes among Methicillin-resistant Staphylococcus Aureus with Inducible Resistance to Clindamycin.

The emergence of Methicillin-resistant Staphylococcus aureus and its ability to confer cross-resistance to macrolide-lincosamide-streptogramin B has complicated the treatment against it. Gene-based studies among phenotypic methicillin-resistant isolates with inducible resistance to clindamycin are less available in Nepal. This work was undertaken to detect the mecA and erm genes among such phenotypes isolated from clinical samples. S. aureus isolated from different clinical samples was identified by standard microbiological procedures (Gram-staining, colony morphology, and different biochemical tests). Methicillin-resistant and inducible resistant to clindamycin phenotypes were detected by using cefoxitin disc (30 µg) and a double disk diffusion test according to the Clinical and Laboratory Standards Institute guidelines and mecA and erm genes were detected by polymerase chain reaction. Among 120 S. aureus isolates, 51.67% (n=62) were MRSA, and the prevalence of inducibly-resistant, constitutively-resistant and Macrolide-Streptogramin phenotypes were 15.83% (n=19), 28.33% (n=34) and 15.83% (n=19) respectively. While 35.84% (n=43) of isolates showed sensitivity to both antibiotics, erythromycin and clindamycin. Out of 14 inducibly-resistant phenotypes, 57.14% (n=8) were found carrying ermC and 28.57% (n=4) phenotypes contained both ermA and ermC. All phenotypes were positive for the mecA gene. Macrolides-Lincosamide-Streptogramin B resistance was predominant among methicillin-resistant S. aureus. While all isolates with inducible clindamycin resistance harbored mecA gene, most of them also harbored ermC gene. The higher prevalence of inducible-resistant to clindamycin indicated the need for rational use of antimicrobial agents.

Does repeated exposure to hydrogen peroxide induce Candida auris resistance?

BackgroundTo minimize environmental colonization by microorganisms that may persist and thrive in healthcare settings, thus reducing healthcare-associated infections (HAIs), new insights over already known biocides are certainly of relevance. Although the efficacy of hydrogen peroxide (H2O2) against the emergent yeast Candida auris is moderately documented, concerns over the potential induction of resistance after repeated exposure do persist. The main objective of the present study was to evaluate the hypothetical induction of Candida auris resistance following 30 days of consecutive exposure to lethal and sublethal concentrations of H2O2. Furthermore, the authors aimed to elucidate about the rank of efficacy of H2O2 against C. auris comparing to other Candida species and whether different strains of C. auris may display different susceptibilities to H2O2.MethodsDuring the induction of resistance assays, both type strains and clinical isolates of Candida auris, Candida albicans and Candida parapsilosis were exposed repeatedly to defined concentrations of H2O2, for 30 days.ResultsAfter that period, no significant differences were found when comparing the minimal inhibitory concentration values of H2O2 in case of the induced strains versus each respective positive control. Moreover, H2O2 displayed similar effectiveness against all the tested Candida species and no differences were demonstrated among the distinct strains of C. auris.ConclusionsThe adoption of H2O2 solutions in routine protocols in order to promote disinfection standards against Candida auris, improving patient safety and reducing healthcare costs, is certainly welcomed.

Strigolactones GR-24 and Nijmegen Applications Result in Reduced Susceptibility of Tobacco and Grapevine Plantlets to Botrytis cinerea Infection.

Priming agents are plant defence-inducing compounds which can prompt a state of protection but may also aid in plant growth and interactions with beneficial microbes. The synthetic strigolactones (±)-GR24 and Nijmegen-1 were evaluated as potential priming agents for induced resistance against Botrytis cinerea in tobacco and grapevine plants. The growth and stress response profiles of B. cinerea to strigolactones were also investigated. Soil drench treatment with strigolactones induced resistance in greenhouse-grown tobacco plants and restricted lesion development. The mode of action appeared to function by priming redox-associated compounds to produce an anti-oxidant protective response for limiting the infection. The results obtained in the in vitro assays mirrored that of the greenhouse-grown plants. Exposure of B. cinerea to the strigolactones resulted in increased hyphal branching, with (±)-GR24 stimulating a stronger effect than Nijmegen-1 by affecting colony diameter and radial growth. An oxidative stress response was observed, with B. cinerea exhibiting increased ROS and SOD levels when grown with strigolactones. This study identified the application of strigolactones as potential priming agents to induce disease resistance in both tobacco and grapevine plants. In addition, strigolactones may alter the ROS homeostasis of B. cinerea, resulting in both morphological and physiological changes, thereby reducing virulence.

Elevated CO2 alters photosynthesis, growth and susceptibility to powdery mildew of oak seedlings.

Elevated CO2 (eCO2) is a determinant factor of climate change and is known to alter plant processes such as physiology, growth and resistance to pathogens. Quercus robur, a tree species integrated in most forest regeneration strategies, shows high vulnerability to powdery mildew (PM) disease at the seedling stage. PM is present in most oak forests and it is considered a bottleneck for oak woodland regeneration. Our study aims to decipher the effect of eCO2 on plant responses to PM. Oak seedlings were grown in controlled environment at ambient (aCO2, ∼400 ppm) and eCO2 (∼1000 ppm), and infected with Erysiphe alphitoides, the causal agent of oak PM. Plant growth, physiological parameters and disease progression were monitored. In addition, to evaluate the effect of eCO2 on induced resistance (IR), these parameters were assessed after treatments with IR elicitor β-aminobutyric acid (BABA). Our results show that eCO2 increases photosynthetic rates and aerial growth but in contrast, reduces root length. Importantly, under eCO2 seedlings were more susceptible to PM. Treatments with BABA protected seedlings against PM and this protection was maintained under eCO2. Moreover, irrespectively of the concentration of CO2, BABA did not significantly change aerial growth but resulted in longer radicular systems, thus mitigating the effect of eCO2 in root shortening. Our results demonstrate the impact of eCO2 in plant physiology, growth and defence, and warrant further biomolecular studies to unravel the mechanisms by which eCO2 increases oak seedling susceptibility to PM.

Assessment of antidiabetic activity of three Phenylspirodrimanes from fungus Stachybotrys chartarum MUT 3308 by ADME, QSAR, molecular docking and molecular dynamics simulation studies against protein tyrosine phosphatase 1B (PTP1B)

Phenylspirodrimanes (PSD) are the sesquiterpene quinone type meroterpenoids found in nature. PSDs are found to exhibit inhibitory activity against immunocomplex diseases, and tyrosine kinase receptors. Three of the different PSDs C1, C2, and C3 that have been reported to be isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308 are selected for studying their possible inhibitory effect against type 2 diabetes mellitus. Mechanistically, blocking protein tyrosine phosphatase 1B (PTP1B) helps to reduce the insulin resistance induction caused by the high expression of PTP1B. The QSAR, ADME, toxicity (T) study was carried out to predict the pharmacokinetic properties and the biological activities of the PSDs. PASS prediction web tool was used to find and select the target proteins 1NNY, and 2HNP. According to the molecular docking simulations, C1 and C2 showed better binding affinity of −8.5 kcal/mol, and −8.1 kcal/mol respectively against 1NNY compared to the control ligand. RMSD, RMSF, Rg, and SASA analysis revealed that both C1, and C2 showed better stability, minor conformational changes, and minor fluctuation upon binding to PTP1B. Protein contact analysis was carried out to validate the residues that are in contact with the ligands according to molecular docking studies. Overall, C1, and C2 could be proposed as novel natural hits to be developed and small modifications of these PSDs could result in inducing the binding affinity significantly, although experimental validation is required for further evaluation of the work. Communicated by Ramaswamy H. Sarma

BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity.

The emergence of drug-resistant superbugs has necessitated a pressing need for innovative antibiotics. Antimicrobial peptides (AMPs) have demonstrated broad-spectrum antibacterial activity, reduced susceptibility to resistance, and immunomodulatory effects, rendering them promising for combating drug-resistant microorganisms. This study employed computational simulation methods to screen and design AMPs specifically targeting ESKAPE pathogens. Particularly, AMPs were rationally designed to target the BamA and obtain novel antimicrobial peptide sequences. The designed AMPs were assessed for their antibacterial activities, mechanisms, and stability. Molecular docking and dynamics simulations demonstrated the interaction of both designed AMPs, 11pep and D-11pep, with the β1, β9, β15, and β16 chains of BamA, resulting in misfolding of outer membrane proteins and antibacterial effects. Subsequent antibacterial investigations confirmed the broad-spectrum activity of both 11pep and D-11pep, with D-11pep demonstrating higher potency against resistant Gram-negative bacteria. D-11pep exhibited MICs of 16, 8, and 32μg/mL against carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and multi-drug-resistant Acinetobacter baumannii, respectively, with a concomitant lower resistance induction. Mechanism of action studies confirmed that peptides could disrupt the bacterial outer membrane, aligning with the findings of molecular dynamics simulations. Additionally, D-11pep demonstrated superior stability and reduced toxicity in comparison to 11pep. The findings of this study underscore the efficacy of rational AMP design that targets BamA, along with the utilization of D-amino acid replacements as a strategy for developing AMPs against drug-resistant bacteria.

Glucose Rate-of-Change and Insulin-on-Board Jointly Weighted Zone Model Predictive Control.

We present design and evaluation of closed-loop insulin delivery using zone model predictive control (MPC) featuring an adaptive weighting scheme to address prolonged hyperglycemia due to changes in insulin sensitivity, underdelivery from profile mismatch, and meal composition. In the MPC cost function, the penalty on predicted glucose deviation from the upper zone boundary is weighted by a joint function of predicted glucose rate-of-change (ROC) and insulin-on-board (IOB). The asymmetric weighting gradually increases when glucose ROC and IOB were jointly low, independent of glucose magnitude, to limit hyperglycemia while aggressively reduces for negative glucose ROC to avoid hypoglycemia. The proposed controller was evaluated using two simulation scenarios: an induced resistance scenario and a nominal scenario to highlight the performance over a reference zone MPC with glucose ROC weighting only. The continuous adaption scheme resulted in consistent improvement for the entire glucose range without incurring additional risk of hypoglycemia. For the induced resistance and no feedforward bolus scenario, the percent time in 70-180 mg/dL was higher (53.5% versus 48.9%, p<0.001) with larger improvement in the overnight percent time in tighter glucose range 70-140 mg/dL (70.9% versus 52.9%, p<0.001). The results from extensive simulations, as well as clinical validation in three different outpatient studies demonstrate the utility and safety of the proposed zone MPC.

Distribution of Macrolide, Lincosamide, and Streptogramin B and Detection of erm Genes in Staphylococcus aureus from Wounds in Uyo, Nigeria

The increasing resistance to macrolide, lincosamide, and streptogramin B (MLSB) among methicillin-resistant Staphylococcus aureus (MRSA) is a challenge. The study determined the constitutive and inducible MLSB resistance and erm genes in S. aureus from wounds using the erythromycin-clindamycin D-zone test and a multiplex polymerase chain reaction assay, respectively. Of the 260 patients recruited in the study, S. aureus was isolated from the wounds of 102 patients, giving a prevalence rate of 39.2%. Of the 102 S. aureus isolates, 32.4% were methicillin-sensitive S. aureus (MSSA), and 67.6% were MRSA. The prevalence of S. aureus in wounds was higher in females (39.8%) than in males (38.4%). The highest prevalence of S. aureus was found in divorce patients (59.1%) and those residing in urban areas (39.7%). There was no statistical difference between the occurrence of MRSA and MSSA in wounds based on the sex (p = 0.97), age (p = 0.08), and marital status (p = 0.41) of the patients. All (100%) MRSA were resistant to Cefoxitin, and chloramphenicol, while ˂ 50% of MRSA were resistant to Tetracycline, Ciprofloxacin, and Gentamycin. Of the 69 MRSA isolates from the wounds, 21.7% and 26.1% were iMLSB and cMLSB phenotypes, respectively. Nine (9) MSSA were iMLSB phenotypes, and eight MSSA were cMLSB phenotypes. Among the 12 representative isolates, three (3) MRSA and one (1) MSSA isolate possessed the ermC gene. This study has revealed that screening tests for iMLSB-resistant S. aureus strains are critical for the therapeutic management of wound infections caused by S. aureus.