Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria.

Thermorubin (THB) is a long-known broad-spectrum ribosome-targeting antibiotic, but the molecular mechanism of its action was unclear. Here, our precise fast-kinetics assays in a reconstituted Escherichia coli translation system and 1.96 Å resolution cryo-EM structure of THB-bound 70S ribosome with mRNA and initiator tRNA, independently suggest that THB binding at the intersubunit bridge B2a near decoding center of the ribosome interferes with the binding of A-site substrates aminoacyl-tRNAs and class-I release factors, thereby inhibiting elongation and termination steps of bacterial translation.

Mechanistic insights into translation inhibition by aminoglycoside antibiotic arbekacin.

How aminoglycoside antibiotics limit bacterial growth and viability is not clearly understood. Here we employ fast kinetics to reveal the molecular mechanism of action of a clinically used, new-generation, semisynthetic aminoglycoside Arbekacin (ABK), which is designed to avoid enzyme-mediated deactivation common to other aminoglycosides. Our results portray complete picture of ABK inhibition of bacterial translation with precise quantitative characterizations.

Kinetic Analysis Suggests Evolution of Ribosome Specificity in Modern Elongation Factor-Tus from "Generalist" Ancestors.

It has been hypothesized that early enzymes are more promiscuous than their extant orthologs. Whether or not this hypothesis applies to the translation machinery, the oldest molecular machine of life, is not known. Efficient protein synthesis relies on a cascade of specific interactions between the ribosome and the translation factors.

Ugly bugs in healthy guts! Carriage of multidrug-resistant and ESBL-producing commensal Enterobacteriaceae in the intestine of healthy Nepalese adults.

Background: Fecal carriage of multidrug-resistant and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is one of the important risk factors for infection with antibiotic-resistant bacteria. In this report, we examined the prevalence of multidrug-resistant and ESBL-producing common enterobacterial strains colonizing the intestinal tract of apparently healthy adults in Kathmandu, Nepal.

Methods: During a 6-month period (February-July 2016), a total of 510 stool specimens were obtained from apparently healthy students of Manmohan Memorial Institute of Health Sciences, Kathmandu, Nepal.

Isolation of Potential Phages against Multidrug-Resistant Bacterial Isolates: Promising Agents in the Rivers of Kathmandu, Nepal.

Bacteriophages are being the subject of interest for alternative antimicrobial therapy for infectious diseases in recent years. Therapeutic effectiveness regarding phage therapy is a matter of concern since it is the most promising biological treatment of this era. Hence, the present study was aimed to isolate the potential bacteriophages present in river water samples and to analyze their host range among clinical strains of bacteria.

Enteric Fever Caused by Serovars with Reduced Susceptibility of Fluoroquinolones at a Community Based Teaching Hospital of Nepal.

Enteric fever continues to be an important public health problem especially in developing countries of the tropical region including Nepal. In this study, we aimed to investigate the incidence of enteric fever associated with and determine its antimicrobial susceptibilities to therapeutic antimicrobials in a community based teaching hospital of Nepal. A total of 2,304 blood samples from suspected enteric fever patients attending Manmohan Memorial Teaching Hospital were processed with standard microbiological methods for the isolation and identification of bacterial pathogens.

Renaissance of Conventional First-Line Antibiotics in Clinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal.

Enteric fever caused by is a life-threatening systemic illness of gastrointestinal tract especially in tropical countries. Antimicrobial therapy is generally indicated but resistance towards commonly used antibiotics has limited their therapeutic usefulness. Therefore, we aimed to determine the antimicrobial susceptibility pattern by minimum inhibitory concentration method of common therapeutic regimens against from enteric fever clinical cases.

High Burden of Antimicrobial Resistance among Bacteria Causing Pyogenic Wound Infections at a Tertiary Care Hospital in Kathmandu, Nepal.

Pyogenic wound infections are one of the most common clinical entities caused and aggravated by the invasion of pathogenic organisms. Prompt and aggressive antimicrobial therapy is needed to reduce the burden and complications associated with these infections. In this study, we intended to investigate the common pathogens and their antimicrobial susceptibility patterns from the pyogenic wound infections at a tertiary care hospital in Kathmandu, Nepal.

High burden of antimicrobial resistance among gram negative bacteria causing healthcare associated infections in a critical care unit of Nepal.

Background: Healthcare associated infections (HCAI) and antimicrobial resistance are principal threats to the patients of intensive care units and are the major determining factors for patient outcome. They are associated with increased morbidity, mortality, excess hospitalization and financial costs. The present study is an attempt to investigate the spectrum and antimicrobial resistance of bacterial isolates involved in healthcare associated infections (HCAI) in the patients of a critical care unit at a tertiary care university hospital in Kathmandu, Nepal.

Elevated Cardiovascular Risks among Postmenopausal Women: A Community Based Case Control Study from Nepal.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide which is more prevalent in women after menopause. Hormonal changes associated with menopause are accountable for dyslipidemic pattern that causes CVD and associated complications. Therefore, the present study was commenced to compare the lipid profile in pre- and postmenopausal women.

Evaluating the Trends of Bloodstream Infections among Pediatric and Adult Patients at a Teaching Hospital of Kathmandu, Nepal: Role of Drug Resistant Pathogens.

Bloodstream infections (BSIs) are among the significant causes of morbidity and mortality for patients of all age groups. However, very little is known about the trends of bacterial bloodstream infections and antimicrobial susceptibilities among pediatric and adult population from Nepal. In this study, we have investigated the different etiological agents responsible for bloodstream infections among pediatric and adult patients and the role of drug resistant organisms in these infections at a tertiary care teaching hospital of Kathmandu, Nepal.

Shigellosis Caused by CTX-M Type ESBL Producing in Two Siblings of Rural Nepal: First Case Report from the Country.

Shigellosis is an acute infectious disease characterized as severe bloody diarrhea (dysentery) and is accountable for a significant burden of morbidity and mortality especially in children under the age of 5 years. Antimicrobial therapy is required in the cases of severe dysentery associated with . However, emergence of multidrug resistant (MDR) strains of spp.

Emerging Perils of Extended Spectrum -Lactamase Producing Enterobacteriaceae Clinical Isolates in a Teaching Hospital of Nepal.

. Infections due to extended spectrum -lactamase producing Enterobacteriaceae are on the rise. They pose serious public health problems due to their resistance to large number of antibiotics.

High rates of multidrug resistance among uropathogenic in children and analyses of ESBL producers from Nepal.

Background: Emergence of Extended-spectrum beta-lactamase producing causing urinary tract infections (UTI) among pediatric patients is an increasing problem worldwide. However, very little is known about pediatric urinary tract infections and antimicrobial resistance trend from Nepal. This study was conducted to assess the current antibiotic resistance rate and ESBL production among uropathogenic in pediatric patients of a tertiary care teaching hospital of Nepal.

Bacteremia caused by a rare pathogen - : a case report from Nepal.

is a gram negative saprophytic bacterium, prevalent in tropical and subtropical climates. Infections caused by are very uncommon, yet it can cause severe systemic infections with higher mortality when entered into the bloodstream through open wound. A case of symptomatic bacteremia in a woman caused by was identified recently at a tertiary care teaching hospital in Nepal.