Drug Resistance In Pathogenic Microorganisms Research Articles

Synthesis of citral-tryptamine fused selenium nanospheres (CT@SeNP's) and exploration of their anticancer, antibacterial, and electrochemical sensor applications

A broad spectrum of antibiotics with multiple mechanisms of action is urgently required to combat the growing public health threat posed by drug-resistant pathogenic microorganisms. Biomedical researchers have concentrated on creating novel antibacterial and anticancer therapies due to the limited availability of conventional antibacterial and anticancer medications. In this study citral-tryptamine molecule was synthesized and characterized using 1HNMR , 13CNMR , LCMS and FT-IR spectral techniques and various biological properties of synthesized molecules were investigated using several in silico approaches such as molecular docking, ADME, PASS analysis and bioactive score. Using citral-tryptamine molecule, selenium nanoparticles (CT@SeNP's) were synthesized and characterized using different spectral and imaging techniques such as UV–Visible spectra, SEM, FTIR, EDX, XRD and DLS. EDX and mapping were used to investigate the relevant atoms and their distribution. Three significant signals from the EDX corresponding to C atom (15.4 %), along with signals from the Se atom (80.9 %) and the N atom (3.7 %). CT@SeNP's showed excellent antibacterial property against MRSA. The minimum inhibitory concentration of CT@SeNP's was found to be 20±0.36 mm with a good zone of inhibition in a dose dependent manner. CT@SeNP's was treated with both normal and cervical cancer cell lines such as SiHa to investigate the dose optimization and cytotoxicity by MTT assay. The nanoparticle showed an IC50 value is 0.68 µM and the data strongly suggested that CT@SeNP's could have a high potential in future medication development against MRSA and cervical cancer cells. The proper development and manufacturing of electrocatalytic nanomaterials are essential for enhancing the performance of non-enzymatic electrochemical sensors. The electrochemical sensing of H2O2 was enhanced by nanocomposite CT@SeNPs, which have a low detection limit of 60.96 nM and can detect H2O2 in a wide range of concentrations, from 25 µM to 250 µM. Thus, an efficient sensing platform for non-enzymatic H2O2 detection was discovered by this investigation.

Inhibition of Pseudomonas aeruginosa quorum sensing by methyl gallate from Mangifera indica

Antipathogenic drugs are a potential source of therapeutics, particularly following the emergence of multiple drug-resistant pathogenic microorganisms in the last decade. The inhibition of quorum sensing (QS) is an advanced antipathogenic approach for suppression of bacterial virulence and dissemination. This study aimed to investigate the inhibitory effect of some Egyptian medicinal plants on the QS signaling system of Pseudomonas aeruginosa. Among the tested plants, Mangifera indica exhibited the highest quorum sensing inhibition (QSI) activity against Chromobacterium violaceum ATCC 12472. Four pure compounds were extracted and identified; of these, methyl gallate (MG) showed the most potent QSI. MG had a minimum inhibitory concentration (MIC) of 512 g/mL against P. aeruginosa strains PAO1, PA14, Pa21, Pa22, Pa23, Pa24, and PAO-JP2. The virulence factors of PAO1, PA14, Pa21, Pa22, Pa23, and Pa24 were significantly inhibited by MG at 1/4 and 1/2 sub-MICs without affecting bacterial viability. Computational insights were performed by docking the MG compound on the LasR receptor, and the QSI behavior of MG was found to be mediated by three hydrogen bonds: Trp60, Arg61, and Thr75. This study indicates the importance of M. indica and MG in the inhibition and modulation of QS and QS-related virulence factors in P. aeruginosa.

Harnessing Efficient ROS Generation in Carbon Dots Derived from Methyl Red for Antimicrobial Photodynamic Therapy.

The emergence of drug-resistant pathogenic microorganisms has become a public health concern, with demand for strategies to suppress their proliferation in healthcare facilities. The present study investigates the physicochemical and antimicrobial properties of carbon dots (CD-MR) derived from the methyl red azo dye. The morphological and structural analyses reveal that such carbon dots present a significant fraction of graphitic nitrogen in their structures, providing a wide emission range. Based on their low cytotoxicity against mammalian cells and tunable photoluminescence, these carbon dots are applied to bioimaging in vitro living cells. The possibility of using CD-MR to generate reactive oxygen species (ROS) is also analyzed, and a high singlet oxygen quantum efficiency is verified. Moreover, the antimicrobial activity of CD-MR is analyzed against pathogenic microorganisms Staphylococcus aureus, Candida albicans, and Cryptococcus neoformans. Kirby-Bauer susceptibility tests show that carbon dots synthesized from methyl red possess antimicrobial activity upon photoexcitation at 532 nm. The growth inhibition of C. neoformans from CD-MR photosensitization is investigated. Our results show that N-doped carbon dots synthesized from methyl red efficiently generate ROS and possess a strong antimicrobial activity against healthcare-relevant pathogens.

Universal Stress Proteins: From Gene to Function

Universal stress proteins (USPs) exist across a wide range of species and are vital for survival under stressful conditions. Due to the increasingly harsh global environmental conditions, it is increasingly important to study the role of USPs in achieving stress tolerance. This review discusses the role of USPs in organisms from three aspects: (1) organisms generally have multiple USP genes that play specific roles at different developmental periods of the organism, and, due to their ubiquity, USPs can be used as an important indicator to study species evolution; (2) a comparison of the structures of USPs reveals that they generally bind ATP or its analogs at similar sequence positions, which may underlie the regulatory role of USPs; and (3) the functions of USPs in species are diverse, and are generally directly related to the stress tolerance. In microorganisms, USPs are associated with cell membrane formation, whereas in plants they may act as protein chaperones or RNA chaperones to help plants withstand stress at the molecular level and may also interact with other proteins to regulate normal plant activities. This review will provide directions for future research, focusing on USPs to provide clues for the development of stress-tolerant crop varieties and for the generation of novel green pesticide formulations in agriculture, and to better understand the evolution of drug resistance in pathogenic microorganisms in medicine.

Contemporary Tools for the Cure against Pernicious Microorganisms: Micro-/Nanorobots

One of the most pressing concerns to global public health is the emergence of drug-resistant pathogenic microorganisms due to increased unconscious antibiotic usage. With the rising antibiotic resistance, existing antimicrobial agents lose their effectiveness over time. This indicates that newer and more effective antimicrobial agents and methods should be investigated. Many studies have shown that micro-/nanorobots exhibit promise in the treatment of microbial infections with their great properties, such as the intrinsic antimicrobial activities owing to their oxidative stress induction and metal ion release capabilities, and effective and autonomous delivery of antibiotics to the target area. In addition, they have multiple simultaneous mechanisms of action against microbes, which makes them remarkable in antimicrobial activity. This review focuses on the antimicrobial micro-/nanorobots and their strategies to impede biofilm formation, following a brief introduction of the latest advancements in micro-/nanorobots, and their implementations against various bacteria, and other microorganisms.

Emergency medicine: past, present, and future challenges

Emergency medicine: past, present, and future challenges

Basic Mechanisms of Antibiotic Resistance: Molecular Properties of Multidrug Transporters

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Physics Comes to the Aid of Medicine-Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope.

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.

Public Toilets in a tertiary institution in the Southern part of Nigeria as Potential Reservoirs of Drug Resistant Pathogens

Toilets have long been viewed as a significant potential contributor to human infectious diseases. Various studies worldwide have explored the bacterial communities associated with toilets but only few have focused on their possible role as reservoirs of drug resistant pathogens. To explore this role, four different surfaces from a pay-to-use toilet complex at a tertiary institution in the Southern part of Nigeria were sampled using the swab-rinse technique. Sample processing was done to determine bacterial load, identify bacterial types present in the samples and determine antibiotic susceptibility using standard techniques. Similar levels of bacterial contamination were observed at all the 14 sampling points ranging from 3.6×104 to 2.7×105 CFU. A higher level of contamination was generally noted on the door handles and floor surfaces. Of the ten different bacterial groups identified, Shigella sp. and Salmonella sp. were the predominant groups (20.6% each). The test isolates showed a wide rate of resistance to antibiotics, with the highest observed against ofloxacin (98.3%) and the least against ceftriaxone (44.4%). Forty-three different antibiogram patterns were detected among the test isolates. Most of the bacteria (63.2%) were associated with MAR index values greater than 0.8. This study shows that public toilets could play a role not just as a reservoir of potential pathogens but more specifically as a potential reservoir of drug resistant pathogenic microorganisms with high MAR indices.
 Keywords: Toilet, Reservoir, MAR index, Nigeria

Free Radical Scavenging Activity of Copper Nanoparticles Synthesized from Dried Ginger

Nano science is considered to be an important area in research in which developing nontoxic, reliable and ecofriendly synthesis of nanoparticles by the green approach has a vital part. Nanoparticles that contain antimicrobial and antioxidant properties are considered to be a new trend for developing therapeutic agents that help in killing drug resistant pathogenic microorganisms. The present study is focused on discovering the antioxidant properties of copper nanoparticles synthesized from dried ginger. Dried ginger is a traditional medicine used widely and has shown to possess good antioxidant and antimicrobial properties. The phytochemical compounds of dried ginger can act as a reducing agent to synthesize copper nanoparticles. Copper nanoparticles were preferred for this study as it has unique physical and chemical properties. There are various methods used to synthesize nanoparticles and here in this study we have used the green synthesis method for synthesizing the copper nanoparticles. The copper nanoparticles were characterized by UV-vis spectroscopy and its antioxidant property was evaluated by DPPH assay.

Biologically rapid synthesis of silver nanoparticles by Sphingobium sp. MAH-11T and their antibacterial activity and mechanisms investigation against drug-resistant pathogenic microbes

The present study highlights the biological synthesis of silver nanoparticles (AgNPs) using Sphingobium sp. MAH-11 and also their antibacterial mechanisms against drug-resistant pathogenic microorganisms. The nanoparticle synthesis method used in this study was reliable, facile, rapid, cost-effective and ecofriendly. The AgNPs exhibited the highest absorbance at 423 nm. The TEM image expressed spherical shape of AgNPs and the size of synthesized AgNPs was 7–22 nm. The selected area diffraction (SAED) pattern and XRD spectrum revealed the crystalline structure of AgNPs. The results of FTIR analysis disclosed the functional groups responsible for the reduction of silver ion to metal nanoparticles. The biosynthesized AgNPs showed strong anti-microbial activity against drug-resistant pathogenic microorganisms. Moreover, Escherichia coli and Staphylococcus aureus were used to explore the antibacterial mechanisms of biosynthesized AgNPs. Minimal inhibitory concentrations (MICs) of E. coli and S. aureus were 6.25 μg/mL and 50 μg/mL, respectively and minimum bactericidal concentrations (MBCs) of E. coli and S. aureus were 25 μg/mL and 100 μg/mL, respectively. Results exhibited that biosynthesized AgNPs caused morphological changes and injured the membrane integrity of strains E. coli and S. aureus. The AgNPs synthesized by Sphingobium sp. MAH-11 may serve as a potent antimicrobial agent for many therapeutic applications.

Mechanism of action and bioactivities of Cinnamomum zeylanicum essential oil against some pathogenic microbes

Background and objective The emergence of multiple drug-resistant pathogenic microorganisms leads to the search for new, safe, and effective therapeutic substances. Essential oils (EOs) of the cinnamon species are known for their biological antimicrobial and antioxidant properties. Therefore, in our study, the EO extracted from the bark of wild Cinnamomum zeylanicum grown in the green mountains of Oman was investigated to study both the aspects. Materials and methods Chemical composition of the EO was analyzed by gas chromatography–mass spectrometry, and then its antimicrobial potential was tested against different Gram-positive, Gram-negative bacteria and fungi. The minimum inhibitory concentration (MIC) was detected and a further in-depth study on the antimicrobial mode of action of the EO at the MIC concentration was studied, in addition to the determination of the antioxidant potential of the studied EO. Results and conclusion Thirty compounds were identified, and the major constituents were cinnamaldehyde (81.78%), bornyl acetate (5.33%), and cinnamyl acetate (2.82%). The antimicrobial results showed a highly significant activity against all tested microbes. The MIC of our EO ranged from 3.3 μl/ml for Gram-positive bacteria and fungi to 10 μl/ml for Gram-negative ones. The mode of action of EO at MIC concentration showed that it had a strong effect on cell viability, permeability of cell membrane, and leakage of cell constituents such as DNA, RNA, and protein from the cell membrane to outside with the lethal percent reaching 99.99%. Moreover, it was observed that the bactericidal and fungicidal effects act in a dose- and time-dependent manner and they depend on the culture condition. Finally, the EO had a strong antioxidant effect with IC50 equaling 2.3 mg. Cinnamon essential oil has a great potential as a useful agent help in combating resistant microorganisms coupled with healing of wounds according to its antioxidant activity.

Attenuation of Vibrio parahaemolyticus Virulence Factors by a Mixture of Natural Antimicrobials.

Reducing acute mortality in aquatic crustaceans using natural alternatives to antibiotics has become a necessity, firstly for its positive impact on the aquaculture industry and, secondly, because the extensive use of antibiotics may lead to increased levels of drug resistance in pathogenic microorganisms. This study aimed to investigate the effect of a mixture of natural antimicrobials on the in vitro and in vivo virulence abilities of Type VI secretion system (T6SS)-positive Vibrio parahaemolyticus (A3 and D4), strains known as having potentially harmful health consequences for aquatic crustaceans and consumers. Herein, we report that a natural antimicrobial mixture (A3009) was capable of significantly reducing the virulence of V. parahaemolyticus strains A3 and D4 in an in vitro infection model, using the fish cell line CHSE-214, an effect which correlates with the bacterial downregulation of hcp1 and hcp2 gene expression and with the ability of the antimicrobial to efficiently retain low cytotoxic levels (p < 0.001). We show for the first time that a natural antimicrobial is able to significantly reduce the mortality of shrimps in a challenge experiment and is able to significantly attenuate H2O2 release during infection (p < 0.001), indicating that it could harbor positive intestinal redox balance effects.

Biotechnological Production of the Cell Penetrating Antifungal PAF102 Peptide in Pichia pastoris.

Antimicrobial peptides (AMPs) have potent and durable antimicrobial activity to a wide range of fungi and bacteria. The growing problem of drug-resistant pathogenic microorganisms, together with the lack of new effective compounds, has stimulated interest in developing AMPs as anti-infective molecules. PAF102 is an AMP that was rationally designed for improved antifungal properties. This cell penetrating peptide has potent and specific activity against major fungal pathogens. Cecropin A is a natural AMP with strong and fast lytic activity against bacterial and fungal pathogens, including multidrug resistant pathogens. Both peptides, PAF102 and Cecropin A, are alternative antibiotic compounds. However, their exploitation requires fast, cost-efficient production systems. Here, we developed an innovative system to produce AMPs in Pichia pastoris using the oleosin fusion technology. Oleosins are plant-specific proteins with a structural role in lipid droplet formation and stabilization, which are used as carriers for recombinant proteins to lipid droplets in plant-based production systems. This study reports the efficient production of PAF102 in P. pastoris when fused to the rice plant Oleosin 18, whereas no accumulation of Cecropin A was detected. The Ole18-PAF102 fusion protein targets the lipid droplets of the heterologous system where it accumulates to high levels. Interestingly, the production of this fusion protein induces the formation of lipid droplets in yeast cells, which can be additionally enhanced by the coexpression of a diacylglycerol transferase gene that allows a three-fold increase in the production of the fusion protein. Using this high producer strain, PAF102 reaches commercially relevant yields of up to 180 mg/l of yeast culture. Moreover, the accumulation of PAF102 in the yeast lipid droplets facilitates its downstream extraction and recovery by flotation on density gradients, with the recovered PAF102 being biologically active against pathogenic fungi. Our results demonstrate that plant oleosin fusion technology can be transferred to the well-established P. pastoris cell factory to produce the PAF102 antifungal peptide, and potentially other AMPs, for multiple applications in crop protection, food preservation and animal and human therapies.

Cave Actinobacteria as Producers of Bioactive Metabolites.

Recently, there is an urgent need for new drugs due to the emergence of drug resistant pathogenic microorganisms and new infectious diseases. Members of phylum Actinobacteria are promising source of bioactive compounds notably antibiotics. The search for such new compounds has shifted to extreme or underexplored environments to increase the possibility of discovery. Cave ecosystems have attracted interest of the research community because of their unique characteristics and the microbiome residing inside including actinobacteria. At the time of writing, 47 species in 30 genera of actinobacteria were reported from cave and cave related habitats. Novel and promising bioactive compounds have been isolated and characterized. This mini-review focuses on the diversity of cultivable actinobacteria in cave and cave-related environments, and their bioactive metabolites from 1999 to 2018.

Cross-cultural Comparison of Medicinal Plants Used to Treat Infections in Northern Thailand

Drug resistance in pathogenic microorganisms threatens both human and animal health. This has prompted the search for new antimicrobial drugs, including the ones from plant-derived medicines. Some researchers have suggested that medicinal plants used by multiple cultures are more likely to be pharmacologically active. We interviewed 808 informants across seven ethnic groups in northern Thailand about their traditional knowledge of medicinal plants. Plants used to treat infections were compared and agreement about a particular use of a plant was evaluated using the “frequency of citation.” When agreements were found between two or more informants, we searched for confirmation in other studies for medicinal uses and biological activities reported for that particular plant species. Of the 808 informants, 103 mentioned 199 distinct plant uses of 143 plant species to treat 21 different “infection” disorders. Of the 199 plant uses, 114 were mentioned by two or more informants; 15 plant uses were shared between different ethnic groups and 55 plant uses were shared within the same ethnic group and had identical or similar uses mentioned in other studies, sometimes in distantly located cultures. The convergent information suggests the bioactivity of a certain plant that may have been discovered independently. However, the remaining 44 plant uses that were shared within the same ethnic group are here reported for the first time with considerable agreement among informants. These new plant uses should be given high priority in bioscreening for new antimicrobial drugs.

Determination of antibacterial activity of essential oils from mint (Mentha spicata) leaves on selected pathogenic bacteria

Drug resistant pathogenic microorganisms account for the highest proportion of death today. This study was aimed at extracting essential oils (EOS) from mint. Sensitivity tests of selected pathogenic microorganism were also carried out. EOS were extracted using distillation method. Phytochemical screening of the essential oils for the presence of tannins, alkaloids, glycosides, flavonoids, resins, phenols and steroids was carried out using standard procedures. Sensitivity test of Staphylococcus aureus (ATCC 25923), Klebsiella pneumoniae (clinical isolate), Escherichia coli ((ATCC 25922), Erwinia carotovora (ATCC 33244), Xanthomonas campestris (ATCC 33913) and Bacillus subtilis (ATCC 6633) to the EOS was carried out using agar well diffusion technique. The minimum inhibitory concentration of the test pathogens by the essential oils was carried out using two-fold serial dilution. The yield of essential oils varied from 1.0±0.01% in first replicate to 3.0±0.03% in the fourth replicate. All the tested phytochemical compounds were present in the EOS of mint. There was no significant difference between the zones of inhibition of the three replicates (F=0.34 P=0.74). In addition, there was no significant difference between the MIC’s of the three replicates (F=0.33 P=0.72). Mint from Egerton University has EOS that can be extracted using distillation method. The EOS were bioactive against the selected bacterial pathogens which creates a need for their mass production.

Tryptophan-Rich and Proline-Rich Antimicrobial Peptides.

Due to the increasing emergence of drug-resistant pathogenic microorganisms, there is a world-wide quest to develop new-generation antibiotics. Antimicrobial peptides (AMPs) are small peptides with a broad spectrum of antibiotic activities against bacteria, fungi, protozoa, viruses and sometimes exhibit cytotoxic activity toward cancer cells. As a part of the native host defense system, most AMPs target the membrane integrity of the microorganism, leading to cell death by lysis. These membrane lytic effects are often toxic to mammalian cells and restrict their systemic application. However, AMPs containing predominantly either tryptophan or proline can kill microorganisms by targeting intracellular pathways and are therefore a promising source of next-generation antibiotics. A minimum length of six amino acids is required for high antimicrobial activity in tryptophan-rich AMPs and the position of these residues also affects their antimicrobial activity. The aromatic side chain of tryptophan is able to rapidly form hydrogen bonds with membrane bilayer components. Proline-rich AMPs interact with the 70S ribosome and disrupt protein synthesis. In addition, they can also target the heat shock protein in target pathogens, and consequently lead to protein misfolding. In this review, we will focus on describing the structures, sources, and mechanisms of action of the aforementioned AMPs.

Drug Resistance in Pathogenic Micro-organisms Isolated from Oral Herbal Medicinal Products and a Survey on the Usage of Herbal Medicine in Bangladesh

Drug Resistance in Pathogenic Micro-organisms Isolated from Oral Herbal Medicinal Products and a Survey on the Usage of Herbal Medicine in Bangladesh

Microbiological quality assessment for drug resistant pathogenic microorganisms from the fresh vended fruit juices

Fruit juices are very popular due to their freshness and taste. These juices contain all the nutritive values those were present in whole fruits. Fresh juices are healthful drink for people of all ages. But the condition is quite opposite if they become contaminated with pathogenic bacteria during the juice processing. Because of the nutritive properties juice can give enough opportunities to the microorganisms to survive and multiply. In our current study we included eight types of fresh juices to study the microbial load. All the samples were heavily contaminated. Total bacterial and fungal count was found to be up to 3.0×107 cfu/ml and 2.6×106 cfu/ml, respectively. Salmonella spp. and Shigella spp. was present only in one sample. Staphylococcus aureus and Pseudomonas spp. were the most prominent in all of the eight samples. Vibrio spp. was found in six samples ranging from 2.0×102 cfu/ml to 2.9×104 cfu/ml. All the pathogenic isolates showed drug resistance towards the most commonly prescribed antibiotics indicating the risk of difficulty in eradicating diseases.Stamford Journal of Microbiology, Vol.6(1) 2016: 7-10