novobiocin and Escherichia-coli-Infections

Topics: Anti-Bacterial Agents; Enterohemorrhagic Escherichia coli; Escherichia coli Infections; Fermented Foods; Food Microbiology; Humans; Novobiocin; RNA, Ribosomal, 16S

Due to increasing emergence of bacterial resistance, compounds with new mechanisms of action are of paramount importance. One of modestly researched therapeutic targets in the field of antibacterial discovery is DNA gyrase B. In the present work we synthesized a focused library of potential DNA gyrase B inhibitors composed of two key pharmacophoric moieties linked by three types of sp

Topics: Adenosine Triphosphate; Anti-Bacterial Agents; Binding Sites; DNA Gyrase; Drug Design; Escherichia coli; Escherichia coli Infections; Humans; Models, Molecular; Topoisomerase II Inhibitors

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and are validated targets for antibacterial drug discovery. Starting from our recently reported 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-based DNA gyrase B inhibitors, we replaced their central core with benzothiazole-2,6-diamine scaffold and interchanged substituents in positions 2 and 6. This resulted in equipotent nanomolar inhibitors of DNA gyrase from Escherichia coli displaying improved inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV from both bacteria. Compound 27 was the most balanced inhibitor of DNA gyrase and topoisomerase IV from both E. coli and S. aureus. The crystal structure of the 2-((2-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzothiazol-6-yl)amino)-2-oxoacetic acid (24) in complex with E. coli DNA gyrase B revealed the binding mode of the inhibitor in the ATP-binding pocket. Only some compounds possessed weak antibacterial activity against Gram-positive bacteria. These results provide a basis for structure-based optimization toward dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

Topics: Anti-Bacterial Agents; Benzothiazoles; Crystallography, X-Ray; DNA Gyrase; DNA Topoisomerase IV; Drug Design; Escherichia coli; Escherichia coli Infections; Humans; Models, Molecular; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship; Topoisomerase II Inhibitors

Toxigenic Escherichia coli (E. coli) are an important cause of gastroenteritis in developing countries. In Ethiopia, gastroenteritis due to food-borne disease is a leading cause of death. Yet, there is no surveillance for E. coli O157 and little is known about the carriage of this pathogen in Ethiopia's livestock. This study aimed to assess the prevalence and levels of antimicrobial resistance of E. coli O157 in goat meat, feces, and environmental samples collected at a large abattoir in the Somali region of Ethiopia. The samples were enriched in modified tryptone broth containing novobiocin, and plated onto sorbitol MacConkey agar. Isolates were confirmed using indole test and latex agglutination. Antimicrobial susceptibility testing was conducted using the disk diffusion method. A total of 235 samples, including 93 goat carcass swabs, 93 cecal contents, 14 water, 20 hand, and 15 knife swabs were collected. Overall, six (2.5%) samples were contaminated with E. coli O157 of which two (2.1%) were isolated from cecal contents, three (3.2%) from carcass swabs, and one (7.1%) from water. All isolates were resistant to at least two of the 18 antimicrobials tested. Two isolates (33.3%) were resistant to more than five antimicrobials. Abattoir facilities and slaughter techniques were conducive to carcass contamination. This study highlights how poor hygiene and slaughter practice can result in contaminated meat, which is especially risky in Ethiopia because of the common practice of eating raw meat. We detect multi-resistance to drugs not used in goats, suggesting that drugs used to treat human infections may be the originators of antimicrobial resistance in livestock in this ecosystem. The isolation of multidrug-resistant E. coli O157 from goats from a remote pastoralist system highlights the need for global action on regulating and monitoring antimicrobial use in both human and animal populations.

Topics: Abattoirs; Animals; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Escherichia coli O157; Ethiopia; Feces; Food Contamination; Food Microbiology; Foodborne Diseases; Goats; Indoles; Livestock; Meat; Microbial Sensitivity Tests; Novobiocin

Plasmid-mediated qnr genes provide only a modest decrease in quinolone susceptibility but facilitate the selection of higher-level resistance. In Escherichia coli strain J53 without qnr, ciprofloxacin resistance often involves mutations in the GyrA subunit of DNA gyrase. Mutations in gyrA were absent, however, when 43 mutants with decreased ciprofloxacin susceptibility were selected from J53(pMG252) with qnrA1. Instead, in 13 mutants, individual and whole-genome sequencing identified mutations in marR and soxR associated with increased expression of marA and soxS and, through them, increased expression of the AcrAB pump, which effluxes quinolones. Nine mutants had increased expression of the MdtE efflux pump, and six demonstrated increased expression of the ydhE pump gene. Many efflux mutants also had increased resistance to novobiocin, another pump substrate, but other mutants were novobiocin hypersusceptible. Mutations in rfaD and rfaE in the pathway for inner core lipopolysaccharide (LPS) biosynthesis were identified in five such strains. Many of the pump and LPS mutants had decreased expression of OmpF, the major porin channel for ciprofloxacin entry. Three mutants had increased expression of qnrA that persisted when pMG252 from these strains was outcrossed. gyrA mutations were also rare when mutants with decreased ciprofloxacin susceptibility were selected from E. coli J53 with aac(6')-Ib-cr or qepA. We suggest that multiple genes conferring low-level resistance contribute to enhanced ciprofloxacin resistance selected from an E. coli strain carrying qnrA1, aac(6')-Ib-cr, or qepA because these determinants decrease the effective ciprofloxacin concentration and allow more common but lower-resistance mutations than those in gyrA to predominate.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Ciprofloxacin; DNA Gyrase; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Lipopolysaccharides; Lipoproteins; Membrane Proteins; Membrane Transport Proteins; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins; Novobiocin; Porins; Repressor Proteins; Trans-Activators; Transcription Factors

We compared the efficiency of universal pre-enrichment broth (UPB), modified Escherichia coli broth containing novobiocin (mEC + n), modified Tryptic Soy Broth (mTSB) and mTSB with novobiocin (mTSB + n) for the enrichment of non-O157 Shiga-toxin-producing E. coli (STEC).. Freeze-injured and control non-O157 STEC (O91, O103, O111, O119, O121, O145 and O165) strains were used to artificially contaminate beef and radish sprout samples, which were then cultivated in each of the four enrichment media. After incubation, STEC strains were detected by loop-mediated isothermal amplification (LAMP) and plating assays. Enrichment in mEC + n was least effective for facilitating the detection of uninjured STEC strains in radish sprouts, while mTSB + n was least effective for enriching freeze-injured non-O157 STEC strains from beef samples for detection by LAMP assay. UPB and mTSB were superior to mEC + n and mTSB + n for the enrichment of non-O157 STEC from food samples.. The enrichment of non-O157 STEC was negatively affected by the addition of novobiocin to enrichment broths.. Novobiocin should not be added to media used for the enrichment of non-O157 STEC in food when cell injury is anticipated.

Topics: Animals; Anti-Bacterial Agents; Bacterial Typing Techniques; Cattle; Culture Media; Escherichia coli Infections; Food Microbiology; Humans; Meat; Novobiocin; Shiga-Toxigenic Escherichia coli; Swine

Fifty-seven Shiga toxin-producing Escherichia coli (STEC) strains isolated from pigs with edema disease (ED) from 1997 to 2001 in Japan were examined for antimicrobial susceptibilities. The susceptibilities were compared with those of E. coli ATCC 23546 isolated from pig with ED in the 1950's. Consequently, the isolated STECs showed high susceptibility to peptides and bicozamycin in a way similar to the reference strain. On the other hand, the STECs showed low susceptibility to beta-lactams, tetracyclines, novobiocin, fosfomycin, trimethoprim, and old quinolones. It became clear that the susceptibilities of the isolated STECs had diminished in regard to antimicrobials.

Topics: 4-Quinolones; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bridged Bicyclo Compounds, Heterocyclic; Edema Disease of Swine; Escherichia coli; Escherichia coli Infections; Fosfomycin; Japan; Lactams; Microbial Sensitivity Tests; Novobiocin; Peptides; Swine; Tetracyclines; Trimethoprim

Several enterohemorrhagic Escherichia coli (EHEC) strains of serotype O157:H7 isolated from patients with hemorrhagic colitis, ischemic colitis, or hemolytic uremic syndrome were all found to be able to invade certain human epithelial cell lines in vitro. Their ability to gain entry into epithelial cells was compared with those of known invasive Shigella flexneri and Salmonella typhi strains and the noninvasive E. coli strain HB101 in invasion assays utilizing gentamicin to kill extracellular bacteria. All EHEC strains under investigation were efficiently internalized into T24 bladder and HCT-8 ileocecal cells. In striking contrast to shigellae, the same EHEC strains were not taken up into human embryonic intestinal INT407 cells or HEp-2 cells any more than the noninvasive E. coli strain HB101. The mechanism(s) of EHEC internalization was characterized by comparing the invasion efficiencies in the absence and presence of a variety of inhibitors acting on structures and processes of prokaryotic or eukaryotic cells. Also, wild-type, plasmid-containing EHEC strains were compared with their plasmid-cured isogenic derivative strains to determine if plasmid genes affect invasion ability. Plasmid-cured EHEC invaded as well as wild-type EHEC, indicating that invasion ability is chromosomally encoded. Inhibition of bacterial protein synthesis by simultaneous addition of bacteria and chloramphenicol to the monolayer blocked EHEC uptake dramatically, suggesting the presence of an invasion protein(s) with a short half-life. Studies utilizing inhibitors which act on eukaryotic cells demonstrated a strong dependence on microfilaments in the process of uptake of all EHEC strains into both T24 and HCT-8 cells. In general, depolymerization of microtubules as well as inhibition of receptor-mediated endocytosis reduced the efficiency of EHEC invasion of T24 cells, whereas interference with endosome acidification reduced EHEC entry into only HCT-8 cells. Taxol-induced stabilization of microtubules did not inhibit internalization into T24 cells or into the HCT-8 cell line. In marked contrast, the ability of S. typhi Ty2 to invade either cell line was inhibited only by depolymerization of microfilaments. In addition to the cell line specificity of EHEC invasion, not all EHEC strains displayed uniform behavior in the presence of inhibitors, suggesting the existence of variant uptake pathways in different strains. Most importantly, previous reports of the inability of EHEC to in

Topics: Actin Cytoskeleton; Bacterial Proteins; Cadaverine; Cell Line; Chloramphenicol; Clathrin; Colitis; Cytoplasm; DNA, Bacterial; Endocytosis; Epithelium; Escherichia coli; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Hemorrhage; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Microtubules; Novobiocin; Receptors, Cell Surface; Rifamycins; RNA, Bacterial; Salmonella typhi; Shigella flexneri

In a prospective study in young women, novobiocin-resistant subgroup-3 micrococci were the second commonest cause, after Escherichia coli; of acute urinary infections. Proteus mirabilis was the only other causative organism. Symptoms, pyuria, or possible aetiological factors were the same in micrococcal and coliform infections. The infecting micrococcus "biotype" was only rarely found among the normal flora of the genitourinary tract of young women, though other micrococci and staphylococci were commonly present. Evidently, the infecting micrococci are selectively pathogenic in the urinary tract. Micrococcal infections, like coliform infections; commonly followed sexual intercourse, but there was no evidence that the micrococci were sexually transmitted. The infecting biotype was rarely found in the male urethra or prepuce.

Topics: Drug Resistance, Microbial; Escherichia coli Infections; Feces; Female; Humans; Male; Micrococcaceae; Novobiocin; Proteus Infections; Proteus mirabilis; Staphylococcal Infections; Sulfamethazine; Urease; Urinary Tract Infections; Urogenital System

Topics: Cephalothin; Colistin; Enterococcus faecalis; Escherichia coli Infections; Gentamicins; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Male; Novobiocin; Postoperative Complications; Prostatectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Streptococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteria; Cephalothin; Chloramphenicol; Cross Infection; Erythromycin; Escherichia coli Infections; Female; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Lincomycin; Male; Microbial Sensitivity Tests; Novobiocin; Oxacillin; Penicillin G; Penicillin Resistance; Proteus Infections; Streptomycin; Sulfates; Tetracycline

Topics: Adult; Chloramphenicol; Diabetes Complications; Escherichia coli Infections; Gangrene; Humans; Leg; Liver Cirrhosis; Male; Novobiocin; Pseudomonas Infections; Skin Transplantation; Sulfacetamide; Tetracycline; Transplantation, Autologous

Topics: Adolescent; Adult; Animals; Escherichia coli; Escherichia coli Infections; Female; Genital Diseases, Female; Humans; Injections, Intramuscular; Kanamycin; Middle Aged; Milk; Novobiocin; Penicillins; Rats; Staphylococcus; Tetracycline

Topics: Anti-Bacterial Agents; Bacitracin; Child; Chloramphenicol; Chlortetracycline; Drainage; Empyema; Erythromycin; Escherichia coli Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Kanamycin; Novobiocin; Oleandomycin; Pediatrics; Penicillins; Pneumococcal Infections; Pneumothorax; Staphylococcal Infections; Streptococcal Infections; Sulfonamides; Surgical Procedures, Operative; Tetracycline; Vancomycin

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Burns; Child; Chloramphenicol; Colistin; Erythromycin; Escherichia coli Infections; gamma-Globulins; Humans; Immune Sera; Infant; Infant, Newborn; Kanamycin; Novobiocin; Polymyxins; Proteus Infections; Pseudomonas Infections; Salmonella Infections; Sepsis; Serum Albumin; Shigella; Sodium Chloride; Solutions; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Vancomycin

Topics: Aeromonas; Alcoholism; Ascites; Bacteremia; Escherichia coli Infections; Geriatrics; Humans; Intestines; Liver Cirrhosis; Liver Function Tests; Neomycin; Novobiocin; Penicillins; Peritonitis; Sepsis; Streptococcal Infections; Streptomycin; Tetracycline

Topics: Alcaligenes; Anti-Bacterial Agents; Chloramphenicol; Colistin; Diabetes Mellitus; Enterobacteriaceae; Escherichia coli Infections; Female; Humans; Kanamycin; Klebsiella; Neomycin; Nitrofurantoin; Novobiocin; Penicillins; Polymyxins; Proteus Infections; Staphylococcal Infections; Streptomycin; Sulfonamides; Tetracycline; Urinary Tract Infections

Topics: Child; Epidemics; Escherichia coli; Escherichia coli Infections; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Nose; Novobiocin; Nurseries, Infant

Topics: Anti-Bacterial Agents; Child; Enteritis; Escherichia coli Infections; Humans; Infant; Novobiocin