Phenotypic and genotypic characterization of colistin-resistant Escherichia Coli with mcr-4, mcr-5, mcr-6, and mcr-9 genes from broiler chicken and farm environment.

BACKGROUND: Colistin is an antibiotic used as a last-resort to treat multidrug-resistant Gram-negative bacterial infections. Colistin had been used for a long time in veterinary medicine for disease control and as a growth promoter in food-producing animals. This excessive use of colistin in food animals causes an increase in colistin resistance. This study aimed to determine molecular characteristics of colistin-resistant Escherichia coli in broiler chicken and chicken farm environments. RESULTS: Four hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia. E. coli was isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detect mcr genes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize the E. coli isolates. Out of the 425 (94%; 425/453) E. coli isolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of the mcr positive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 µg/ml. The most prominent mcr gene detected was mcr-1 (47.9%; 23/48), followed by mcr-8 (18.8%; 9/48), mcr-7 (14.5%; 7/48), mcr-6 (12.5%; 6/48), mcr-4 (2.1%; 1/48), mcr-5 (2.1%; 1/48), and mcr-9 (2.1%; 1/48) genes. One E. coli isolate originating from the fecal sample was found to harbor both mcr-4 and mcr-6 genes and another isolate from the drinking water sample was carrying mcr-1 and mcr-8 genes. The majority of the mcr positive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of the mcr positive E. coli isolates were multidrug resistant. The most frequently detected virulence genes among mcr positive E. coli isolates were ast (38%; 18/48) followed by iss (23%; 11/48). This is the first research to report the prevalence of mcr-4, mcr-5, mcr-6, mcr-7, and mcr-8 genes in E. coli from broiler chickens and farm environments in Malaysia. CONCLUSION: Our findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistant E. coli, posing a risk to public health and food safety.

Dietary supplementation of Salvinia cucullata in white shrimp Litopenaeus vannamei to enhance the growth, nonspecific immune responses, and disease resistance to Vibrio parahaemolyticus.

The current study investigates the effect of ethanolic extract of Salvinia cucullata (EESC) on growth, non-specific immune parameters, and disease resistance to Vibrio parahaemolyticus in Litopenaeus vannamei. The in-vitro cytotoxicity investigation was performed on shrimp hemolymph hemocytes to assess the toxicity and immunological responses with various concentrations of EESC, and no significant difference in cell viability was seen across dosages, but substantial changes in Phenol Oxidase (PO) and phagocytosis were reported. The in-vivo investigation was conducted on white shrimp for 56 days using varied amounts of 0 (control), 5 (EESC5), 10 (EESC10), and 20 (EESC20) g kg-1 containing feeds and challenged against Vibrio parahaemolyticus. The shrimp fed the EESC10 diet gained the most weight, had the highest specific growth rate (SGR) and had a better feed conversion ratio (FCR). The highest cumulative survival percentage was noted on the EESC10 diet-fed shrimps followed by EESC20 and EESC5 groups after the bacterial challenge with V. parahaemolyticus. The results of immune parameters such as total protein, total carbohydrate, coagulation time, total hemocytes count (THC), superoxide dismutase (SOD), ProPO, and phagocytosis levels were better in the EESC10 group. EESC5 and EESC20 groups were also shown better immunomodulatory effects than the control group. In conclusion, the oral administration of EESC was found to be an effective functional feed additive to improve the growth, immune parameters, and disease resistance against V. parahaemolyticus in L.vannamei.

Insights of CRISPR-Cas systems in stem cells: progress in regenerative medicine.

Regenerative medicine, a therapeutic approach using stem cells, aims to rejuvenate and restore the normalized function of the cells, tissues, and organs that are injured, malfunctioning, and afflicted. This influential technology reaches its zenith when it is integrated with the CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) technology of genome editing. This tool acts as a programmable restriction enzyme system, which targets DNA as well as RNA and gets redeployed for the customization of DNA/RNA sequences. The dynamic behaviour of nuclear manipulation and transcriptional regulation by CRISPR-Cas technology renders it with numerous employment in the field of biologics and research. Here, the possible impact of the commonly practiced CRISPR-Cas systems in regenerative medicines is being reviewed. Primarily, the discussion of the working mechanism of this system and the fate of stem cells will be scrutinized. A detailed description of the CRISPR based regenerative therapeutic approaches for a horde of diseases like genetic disorders, neural diseases, and blood-related diseases is elucidated.

AMF and PSB applications modulated the biochemical and mineral content of the eggplants.

This study was conducted to investigate the beneficial role of phosphate solubilizing bacteria (PSB) and arbuscular mycorrhizal fungi (AMF) in improving eggplant fruits' biochemical composition and mineral content. The plants were treated with AMF Acaulospora laevis, and bacteria Pseudomonas fluorescens, and the corresponding variations were measured for mineral content (Ca, Fe, Mg, K, and P), biochemical parameters (dry matter, total soluble solid [TSS], phenolics, chlorogenic acid, vitamin C) along with arbuscular mycorrhiza spore number, and percentage of root colonization. The AMF and PSB-mediated soil and root-associated nutrients become available for uptake via mineralization, solubilization, and mobilization, primarily through the generation of organic acids and P-hydrolysing enzymes by the microbes. All the treatments showed a significant increase in the concentrations of different biochemical components. However, the combination of both A. laevis and P. fluorescens was found to be the most efficient. These results indicated the possibility of A. laevis and P. fluorescens being used as biofertilizers.

Exploring the Bioactive Potentials of C60-AgNPs Nano-Composites against Malignancies and Microbial Infections.

At present, the potential role of the AgNPs/endo-fullerene molecule metal nano-composite has been evaluated over the biosystems in-vitro. The intra-atomic configuration of the fullerene molecule (C60) has been studied in-vitro for the anti-proliferative activity of human breast adenocarcinoma (MDA-MB-231) cell lines and antimicrobial activity against a few human pathogens that have been augmented with the pristine surface plasmonic electrons and antibiotic activity of AgNPs. Furthermore, FTIR revealed the basic vibrational signatures at ~3300 cm-1, 1023 cm-1, 1400 cm-1 for O-H, C-O, and C-H groups, respectively, for the carbon and oxygen atoms of the C60 molecule. NMR studies exhibited the different footprints and magnetic moments at ~7.285 ppm, explaining the unique underlying electrochemical attributes of the fullerene molecule. Such unique electronic and physico-chemical properties of the caged carbon structure raise hope for applications into the drug delivery domain. The in-vitro dose-dependent application of C60 elicits a toxic response against both the breast adenocarcinoma cell lines and pathogenic microbes. That enables the use of AgNPs decorated C60 endo fullerene molecules to design an effective anti-cancerous drug delivery and antimicrobial agent in the future, bringing a revolutionary change in the perspective of a treatment regime.

Thiazolidin-2,4-Dione Scaffold: An Insight into Recent Advances as Antimicrobial, Antioxidant, and Hypoglycemic Agents.

Heterocyclic compounds containing nitrogen and sulfur, especially those in the thiazole family, have generated special interest in terms of their synthetic chemistry, which is attributable to their ubiquitous existence in pharmacologically dynamic natural products and also as overwhelmingly powerful agrochemicals and pharmaceuticals. The thiazolidin-2,4-dione (TZD) moiety plays a central role in the biological functioning of several essential molecules. The availability of substitutions at the third and fifth positions of the Thiazolidin-2,4-dione (TZD) scaffold makes it a highly utilized and versatile moiety that exhibits a wide range of biological activities. TZD analogues exhibit their hypoglycemic activity by improving insulin resistance through PPAR-γ receptor activation, their antimicrobial action by inhibiting cytoplasmic Mur ligases, and their antioxidant action by scavenging reactive oxygen species (ROS). In this manuscript, an effort has been made to review the research on TZD derivatives as potential antimicrobial, antioxidant, and antihyperglycemic agents from the period from 2010 to the present date, along with their molecular mechanisms and the information on patents granted to TZD analogues.

Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19.

In recent decades, the major concern of emerging and re-emerging viral diseases has become an increasingly important area of public health concern, and it is of significance to anticipate future pandemic that would inevitably threaten human lives. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged virus that causes mild to severe pneumonia. Coronavirus disease (COVID-19) became a very much concerned issue worldwide after its super-spread across the globe and emerging viral diseases have not got specific and reliable diagnostic and treatments. As the COVID-19 pandemic brings about a massive life-loss across the globe, there is an unmet need to discover a promising and typically effective diagnosis and treatment to prevent super-spreading and mortality from being decreased or even eliminated. This study was carried out to overview nanotechnology-based diagnostic and treatment approaches for emerging and re-emerging viruses with the current treatment of the disease and shed light on nanotechnology's remarkable potential to provide more effective treatment and prevention to a special focus on recently emerged coronavirus.

HIV prevalence and risk factors in infants born to HIV positive mothers, measured by dried blood spot real-time PCR assay in Tigray, Northern Ethiopia.

BACKGROUND: Infants infected during pregnancy or while breastfeeding requires early HIV diagnosis at 6 weeks after birth to identify HIV infection and timely treatment. The objective of this work was to determine the prevalence and associated risk factors of HIV among HIV exposed infants in the Tigray regional state, Northern Ethiopia. METHODS: A cross-sectional study was conducted on 350 exposed infants born to HIV seropositive mothers from September 01 to December 30, 2016. Convenient consecutive sampling technique was employed to enroll HIV exposed infants from age 6 weeks to 18 months attending prevention of mother to child transmission (PMCT) clinic at Anti Retroviral Therapy (ART) site facility in Tigray, Ethiopia. Sociodemographic data and associated risk factors were collected using a structured questionnaire. Dried Blood Spot (DBS) samples were collected from each infant and transported by post to Tigray Health Research Institute to detect HIV infection using real-time Polymerase Chain Reaction (PCR). Data were entered into EPI Info version 7, exported and analyzed using Statistical Package for Social Sciences (SPSS) version 22. p-value less than 0.05 was deemed to be statistically significant by Fisher's exact test. RESULTS: Three hundred forty infants (175 males, 165 females) met the criteria for selection during the completion of the study and the overall HIV prevalence was found to be 2.1% (n = 7). The majority of infants were from urban areas (n = 246, 72.4%). 45.5% (5/11, p = 0.001) infants were without ARV prophylaxis, 60% (3/5, p = 0.001) infants born to mothers who did not take maternal PMTCT intervention, 43% (3/7, p = 0.001) infants born to mothers who were not enrolled to ART care, and 6.1% (4/66, p = 0.029) infants of unmarried mothers showed statistically significant difference. CONCLUSIONS: The overall prevalence of HIV among exposed infants was high but lower than the Millennium Development Goal targets. In order to eliminate the mother to child HIV transmission (MTCT) ARV prophylaxis in infants must be strengthened, and enrollment of HIV positive pregnant women to PMTCT and ART care and treatment is needed.

Prevalence and Factors Associated with Multidrug-Resistant Tuberculosis (MDR-TB) among Presumptive MDR-TB Patients in Tigray Region, Northern Ethiopia.

BACKGROUND: Tuberculosis (TB) is one of the major public health problems. There are alarming reports of increasing multidrug-resistant tuberculosis (MTR-TB) from various parts of the globe, including Ethiopia. This study was designed to determine the prevalence and factors associated with MDR-TB among presumptive MDR-TB cases in Tigray Regional State, Ethiopia. METHODS: A cross-sectional study was conducted in Tigray Regional State from 2015 to 2016. Two hundred sputum samples were collected, transported, processed using 2% N-acetyl-L-cysteine-sodium hydroxide, and cultured in LJ medium. Besides, the microscopic examination was performed after ZN staining. Moreover, drug susceptibility test was done using molecular line probe assay. Descriptive statistics and binary and multivariable logistic regression were done. A statistical test was regarded as significant when the P value was <0.05. RESULTS: The prevalence of MDR-TB was found to be 18.5%. About one-fourth (26.5%) of the study participants had sputum smear positive for acid-fast bacilli (AFB). TB culture was positive in 37% of the samples, and rifampicin mono-resistant cases accounted for 3.5% of the presumptive MDR-TB cases. Three (1.5%) were new MDR-TB cases, while the rest had been treated previously for TB. Most (63.5%) of the MDR-TB cases were from 15 to 44 years of age. Age was associated with MDR-TB with a crude odds ratio of 1.06 (CI: 1.02-1.10) and adjusted odds ratio of 1.06 (CI: 1.00-1.11). CONCLUSIONS: The prevalence of MDR-TB was found to be high. Preventive measures should be taken to prevent the transmission of MDR-TB in the community.

The prevalence and drug resistance pattern of extended spectrum ß-lactamases (ESBLs) producing Enterobacteriaceae in Africa.

Extended spectrum ß-lactamases (ESBLs) are a group of enzymes that can hydrolyze a variety of ß-lactams including fourth generation cephalosporins and compromise the efficacy of all ß-lactams, except cephamycins and carbapenems. In the worldwide, the ESBL group of enzymes are found widely and causes a severe infection on human health which leads to various diseases. This review primarily focusses on analyzing the prevalence and drug resistance patterns in the African continent. From the earlier reported data shown only the minimal amount of surveillance information's has been summarized with respect to antimicrobial resistance on ESBLs producing Enterobacteriaceae both in hospital and community settings. To bring the present scenario in limelight, the present study explores the prevalence of ESBL-producing Enterobacteriaceae in various countries in Africa and specifically, to identify most common ESBL genes in hospital and community. The observation was initiated with the exhaustive literature search using PubMed and other databases to broaden the study from the earlier investigations in the African countries concerned about the prevalence rate of ESBL producing Enterobacteriaceae. Further, this study was extended to review various hypothesis of the hydrolytic mechanism, which was detailed by several authors performed earlier through computational approaches. Interestingly, the ESBLs class A and D were found to be common classes in Africa, with the gene CTX-M-15 being most prevalent. Notably, the present review highlights the prevalence on individual countries in Africa and it is extremely significant to prevent the dissemination of ESBL-producing Enterobacteriaceaea. Hence, this review on surveillance will be the benchmark to enhance the research on antimicrobial resistance patterns for all classes and genes. Furthermore, explored in-sights in this paper will be helpful for the further investigations to develop quicker, cost effective, and reliable diagnostic strategies and new effective therapies.

Synthesis of silver nanoparticles from Phenerochaete chrysosporium (MTCC-787) and their antibacterial activity against human pathogenic bacteria.

The present study elucidates an eco-friendly method for synthesizing silver nanoparticles using Phenerochaete chrysosporium (MTCC-787), its bactericidal and cytotoxic effect were studied. The formation of nanoparticles was evidenced by color change and UV-Vis spectroscopy. Atomic Force Microscope and Transmission electron microscope, showed spherical and oval shapes particles in the sizes ranging between 34 and 90 nm. The biosynthesised silver nanoparticles showed significant antibacterial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Staphylococcus epidermidis at a high dose. Further, the nanoparticles observed to be non-toxic at 12.5 µg/ml towards fibroblast cells.

Synthesis of silver nanoparticles from Bacillus brevis (NCIM 2533) and their antibacterial activity against pathogenic bacteria.

The present study is focused on the biological synthesis of silver nanoparticles (AgNPs) from the Bacillus brevis (NCIM 2533) was investigated. The synthesized AgNPs were characterized by various spectroscopic and microscopic techniques and confirmed the AgNPs having the surface Plasmon resonance peak at 420 nm and in the size range of 41-68 nm with spherical in shape by AFM and SEM analysis. It was confirmed and ascertained the presence of bioactive compounds in the AgNPs using TLC and FTIR. The In-vitro antibacterial activity of AgNPs showaed potential antibacterial property against multi-drug resistant pathogens such as Salmonella typhi and Staphylococcus aureus. The biosynthesized AgNPs could be utilized as antimicrobial agents for effective disease management.

Photocatalytic properties and antimicrobial efficacy of Fe doped CuO nanoparticles against the pathogenic bacteria and fungi.

Pathogenic microbes are becoming a potential threat to human beings and environment. Owing to the biofilm forming ability, multidrug resistant pathogens have emerged, which has led to increased death and mortality rate. CuO is a transition metal oxide with high captivating property used for various technological applications such as superconductors, gas sensors, photocatalytic applications etc. CuO in the form of nanoparticles (NPs) is a potential candidate against microbial pathogens. Recently, the antimicrobial and antibiofilm properties of CuO have been tested against various pathogenic bacteria and fungi. In the present study, Fe doped CuO synthesized using sol-gel method was tested against pathogenic bacteria and fungus. The synthesized NPs were characterized using XRD, FTIR, SEM and EDAX analysis. The photocatalytic activity of the Fe doped CuO NPs was analysed using UV-Vis and fluorescent light spectroscopic analysis (FL). In vitro analysis was performed to analyze the antimicrobial and antibiofilm potentials of Fe doped CuO NPs against the pathogenic bacteria (Staphylococcus aureus and Staphylococcus epidermidis) and fungus (Candida albicans). Therefore, the present study is the first report showing both antibiofilm and antibacterial activities of Fe doped CuO NPs against bacterial and fungal pathogens.

Review on emergence of drug-resistant tuberculosis (MDR & XDR-TB) and its molecular diagnosis in Ethiopia.

Tuberculosis (TB) remains a major global health problem and ranks as the second leading cause of death among deaths caused by infectious diseases worldwide. Although the availability of short-course regimens as first-line anti-tuberculosis drugs, the emergence of drug-resistant Mycobacterium tuberculosis strains pose a major challenge to the prevention and control efforts of national tuberculosis programs (NTPs). M. tuberculosis changes its cellular environment with the mechanisms that have been evolved since prehistoric times. The interactions between the bacteria and the host environment have been studied well. However, the studies at molecular level began to emerge recently including expression profiling of micro RNA (miRNA) and literature survey revealed that researchers find more information about their regulatory role in biological processes including immune response to infectious agents like mycobacteria. In developing countries, including Ethiopia, the burden of tuberculosis and or drug resistance profile of M. tuberculosis remains largely unexplored, mainly due to lack of quality controlled second-line laboratory tests and also lack of knowledge on molecular diagnostics. This review describes the disease etiology, pathogenesis, epidemiology, molecular mechanism and advanced molecular diagnostics for precision MDR-TB diagnosis.

Role of plant phytochemicals and microbial enzymes in biosynthesis of metallic nanoparticles.

Metal-based nanoparticles have gained tremendous popularity because of their interesting physical, biological, optical, and magnetic properties. These nanoparticles can be synthesized using a variety of different physical, chemical, and biological techniques. The biological means are largely preferred as it provides an environmentally benign, green, and cost-effective route for the biosynthesis of nanoparticles. These bioresources can act as a scaffold, thereby playing the role of reducing as well as capping agents in the biosynthesis of nanoparticles. Medicinal plants tend to have a complex phytochemical constituent such as alcohols, phenols, terpenes, alkaloids, saponins, and proteins, while microbes have key enzymes which can act as reducing as well as stabilizing agent for NP synthesis. However, the mechanism of biosynthesis is still highly debatable. Herein, the present review is directed to give an updated comprehensive overview towards the mechanistic aspects in the biosynthesis of nanoparticles via plants and microbes. Various biosynthetic pathways of secondary metabolites in plants and key enzyme production in microbes have been discussed in detail, along with the underlying mechanisms for biogenic NP synthesis.

Multifunctional theranostic applications of biocompatible green-synthesized colloidal nanoparticles.

Phytochemicals offer immense promise for sustainable development and production of nanotechnology-enabled products. In the present study, Olax nana Wall. ex Benth. (family: Olacaceae) aqueous extract was used as an effective stabilizing agent to produce biogenic silver (ON-AgNPs) and gold nanoparticles (ON-AuNPs), which were investigated for biocompatibility and prospective biomedical applications (antibacterial, anticancer, antileishmanial, enzyme inhibition, antinociceptive, and anti-inflammatory activities). Various characterization techniques (XRD, FTIR, SEM, TEM, DLS, EDX, and SAED) revealed efficient biosynthesis of ON-AgNPs (26 nm) and ON-AuNPs (47 nm). In the toxicological assessment, ON-AgNPs and ON-AuNPs were found biocompatible towards human RBCs and macrophages (IC50 > 200 µg/mL). In a concentration range of 62.5-2000 µg/mL, a strong antibacterial effect was produced by ON-AgNPs against Staphylococcus epidermidis (MIC = 7.14 µg/mL) and Escherichia coli (8.25 µg/mL), while ON-AuNPs was only active against Staphylococcus aureus (9.14 µg/mL). At a concentration of 3.9-500 µg/mL, a dose-dependant inhibition of HepG2 cancer cells was produced by ON-AgNPs (IC50 = 14.93 µg/mL) and ON-AuNPs (2.97 µg/mL). Both ON-AgNPs and ON-AuNPs were found active against Leishmania tropica (KMH23) promastigotes (IC50 = 12.56 and 21.52 µg/mL) and amastigotes (17.44 and 42.20 µg/mL), respectively, after exposure to a concentration range of 1-200 µg/mL for 72 h. Preferential enzyme inhibition against urease and carbonic anhydrase II were noted for ON-AgNPs (39.23 and 8.89%) and ON-AuNPs (31.34 and 6.34%), respectively; however, these were found inactive against xanthine oxidase at 0.2 mg/mL. In the in vivo antinociceptive (acetic acid-induced abdominal constrictions) and anti-inflammatory (carrageenan-induced paw edema) activities, ON-AgNPs and ON-AuNPs at doses of 40 and 80 mg/kg, significantly attenuated the tonic nociception (P < 0.001) and ameliorated the carrageenan-induced inflammation (P < 0.01, P < 0.001). The results of in vitro and in vivo activities indicated that the biogenic nanoparticles can be used as valuable theranostic agents for further exploration of diverse biomedical applications.

Antimicrobial efficacy of drug blended biosynthesized colloidal gold nanoparticles from Justicia glauca against oral pathogens: A nanoantibiotic approach.

Antimicrobial resistance is a challenging task for researchers to develop new strategies. Green synthesis of AuNPs is an eco-friendly approach, which can be utilized in the microbistatic and microbicidal activities. The current study is focused on Justicia glauca (aqueous leaf extract) mediated AuNPs synthesis at room temperature by treating chloroaurate ions, that shows an antagonistic effect with Azithromycin (AZM) and Clarithromycin (CLR) antibiotics against oral pathogenic bacteria and fungi (Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus, Streptococcus mutans, Lactobacillus acidophilus, Escherichia coli, Pseudomonas aeruginosa, Saccharomyces cerevisiae and Candida albicans). Characterization of green synthesized AuNPs was done by using Ultraviolet-visible (UV-vis) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, Transmission Electron Microscopy (TEM), X-Ray Diffraction (XRD) analysis and Energy Dispersive X-ray analysis (EDAX). Biosynthesized AuNPs were stable, hexagonal and spherical shaped with a size ∼32.5 ± 0.25 nm. The AuNPs and drug conjugated AuNPs showed potential antibacterial and antifungal activity against the oral pathogens. Minimum Inhibitory Concentration (MIC) values of biogenic AuNPs were observed in the range of 6.25-25 µg/mL against selected oral pathogens. Overall, we conclude that biogenic drug delivery system for AZM and CLR can be exploited as potential antimicrobial therapy in future, subject to detailed in-vitro and in-vivo cytotoxicity.

Ocular bacterial infections at Quiha Ophthalmic Hospital, Northern Ethiopia: an evaluation according to the risk factors and the antimicrobial susceptibility of bacterial isolates.

BACKGROUND: External and intraocular infections can lead to visual impairments, which is a major public health problem. Bacteria are the most frequent pathogens affecting ocular structures; the increasing rate of antimicrobial drug resistance is a worldwide concern. The aim of this study was to determine the occurrence of bacteria in ocular infections, their antimicrobial susceptibility patterns, and risk factors in bacterial ocular infection. METHODS: A hospital based cross-sectional study was conducted from September 2015 to December 2015 at Quiha Ophthalmic Hospital, Tigray, northern Ethiopia. Ocular specimens from blepharitis, blepharoconjunctivitis, conjunctivitis, keratitis, endophthalmitis, periorbital cellulitis and dacrocystitis were collected from 270 individuals with suspected ocular infection. Data on sociodemographic and risk factors were also collected using a structured questionnaire. Data analysis was performed using SPSS version 21 and 0.05 with a corresponding 95% confidence interval (CI) was considered statistically significant. RESULTS: Among 270 study subjects, 180 (66.7%) were culture positive for different bacterial isolates. The predominant bacterial isolates were Staphylococcus aureus (40, 22.2%), coagulase negative staphylococci (31, 17.2%) and Pseudomonas aeruginosa (21, 11.7%). Ocular surface disease, ocular trauma, hospitalization and cosmetic application practices were significantly associated with the occurrence of bacterial infection. Concerning antimicrobial susceptibility, most isolates were susceptible to amikacin (137, 93.2%), gentamicin (131, 89.1%) and ciprofloxacin (141, 89.2%). Overall, 40 (22.5%), 34 (19.1%) and 62 (34.8%) isolates were resistant to one, two, and three or more antimicrobials, respectively. CONCLUSION: Bacteria were isolated from the majority of the study subjects. More than half of the bacterial isolates were resistant at least to one drug and a significant rate of multidrug resistance was detected. Therefore, identification of the etiologic agent and antimicrobial susceptibility testing should be practiced to select the appropriate antimicrobial agent to treat eye infections and prevent the emergence of drug resistant bacteria.

Bacterial profile of ocular infections: a systematic review.

BACKGROUND: Bacteria are the major contributor of ocular infections worldwide. Ocular infections, if left untreated, can damage the structures of the eye with possible blindness and visual impairments. This work was aimed to review the bacterial profile of ocular infections. METHODS: Literature search was made in different electronic databases; the review was systematically made to get concrete findings. RESULTS: As far as this review, Staphylococcus aureus, Coagulase negative Staphylococci, Streptococcus pneumoniae and Pseudomonas aeruginosa are the leading isolates in ocular infections. Frequent pathogens of the respective clinical diagnose include Staphylococci, Streptococcus pyogenes and Pseudomonas aeruginosa in blepharitis; Staphylococci, Streptococus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli in Conjunctivitis; Staphylococci, P. aeruginosa and E. coli in dacryocystitis; Coagulase negative Staphylococci, Pseudomonas aeruginosa and Staphylococcus aureus in keratitis; Streptococcus viridians, Streptococcus pneumoniae and Coagulase negative Staphylococci in endophthalmitis diagnoses. Endogenous endophthalmitis is associated with Klebsiella pneumoniae whereas Coagulase negative Staphylococci and Bacillus spp. are common causes of post-operative and post-traumatic endophthalmitis. However, the predominant pathogens may not be exactly same in all areas of the world, in the United States for instance, Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae are the major causes of conjunctivitis. CONCLUSION: Gram positive bacteria are the major contributor of bacterial ocular infections. The distribution and proportion of bacterial isolates among clinical diagnoses varied but without exclusive anatomical restriction. To mitigate the burden of bacterial ocular infections, physicians should regard on risk reduction and comply with etiologic approach of diagnosis.

Prediction of deleterious non-synonymous SNPs of TMPRSS2 protein combined with Molecular Dynamics Simulations and free energy analysis to identify the potential peptide substrates against SARS-CoV-2.

Globally the SARS-CoV-2 viral infection demands for the new drugs, the TMPRSS2 target plays a vital role in facilitating the virus entry. The aim of the present study is to identify the potential peptide substrate from the Anti-viral database against TMPRSS2 of SARS-CoV-2. The compound screening and variation analysis were performed using molecular docking analysis and online tools such as PROVEAN and SNAP2 server, respectively. The re-docked crystal structure peptide substrate exhibits -128.151 kcal/mol whereas the RRKK peptide substrate shows -134.158 kcal/mol. Further, the selected compounds were proceeded with Molecular Dynamics Simulation, it explores the stability of the complex by revealing the hotspot residues (His296 and Ser441) were active for nucleophilic attack against TMPRSS2. The average Binding Free Energy values computed through MM/GBSA for RRKK, Camostat, and Crystal Structure were shown -69.9278 kcal/mol, -64.5983 kcal/mol, and -63.9755 kcal/mol, respectively against TMPRSS2. The 'rate of acylation' emerges as an indicator for RRKK's efficacy, it maintains the distance of 3.2 Å with Ser441 resembles, whilst its -NH backbone stabilizes at 2.5 Å 'Michaelis Complex' which leads to prevent the entry of SARS-CoV-2 to human cells. The sequence variation analysis explores that the V160 and G6 substitutions are essential to emphasize the uncover possibilities for the ongoing drug discovery research. Therefore, the identified peptide substrate found to be potent against SARS-CoV-2 and these results will be valuable for ongoing drug discovery research.Communicated by Ramaswamy H. Sarma.