Linear plasmids in Klebsiella and other Enterobacteriaceae

2021 ◽  
Author(s):  
Jane Hawkey ◽  
Hugh Cottingham ◽  
Alex Tokolyi ◽  
Ryan R Wick ◽  
Louise M Judd ◽  
...  
Keyword(s):  
Plasmid Stability ◽  
Bacterial Species ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Linear Plasmid ◽  
Extrachromosomal Dna ◽  
Linear Plasmids ◽  
Future Studies ◽  
And Function

Linear plasmids are extrachromosomal DNA that have been found in a small number of bacterial species. To date, the only linear plasmids described in the Enterobacteriaceae family belong to Salmonella, first found in Salmonella Typhi. Here, we describe a collection of 12 isolates of the Klebsiella pneumoniae species complex in which we identified linear plasmids. We used this collection to search public sequence databases and discovered an additional 74 linear plasmid sequences in a variety of Enterobacteriaceae species. Gene content analysis divided these plasmids into five distinct phylogroups, with very few genes shared across more than two phylogroups. The majority of linear plasmid-encoded genes are of unknown function, however each phylogroup carried its own unique toxin-antitoxin system and genes with homology to those encoding the ParAB plasmid stability system. Passage in vitro of the 12 linear plasmid-carrying Klebsiella isolates in our collection (which include representatives of all five phylogroups) indicated that these linear plasmids can be stably maintained, and our data suggest they can transmit between K. pneumoniae strains (including members of globally disseminated multidrug resistant clones) and also between diverse Enterobacteriaceae species. The linear plasmid sequences, and representative isolates harbouring them, are made available as a resource to facilitate future studies on the evolution and function of these novel plasmids.

scholarly journals Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

2000 ◽  
Vol 44 (10) ◽  
pp. 2645-2652 ◽  
Author(s):  
Mark E. Jones ◽  
Angela M. Staples ◽  
Ian Critchley ◽  
Clyde Thornsberry ◽  
Paul Heinze ◽  
...  
Keyword(s):  
Moraxella Catarrhalis ◽  
The United States ◽  
Multidrug Resistant ◽  
Pulsed Field Gel Electrophoresis ◽  
In Vitro Activity ◽  
Resistant Clone ◽  
Future Studies ◽  
Medical Centers ◽  
Drug Classes

ABSTRACT To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of Streptococcus pneumoniae (5,640), Haemophilus influenzae (6,583), and Moraxella catarrhalis (3,648) referred from 377 institutions during 1998 is described. For S. pneumoniae the modal MIC and MIC at which 90% of the isolates were inhibited (MIC90) for moxifloxacin were 0.12 and 0.25 μg/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations ingyrA and/or parC known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs ≥3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC90 for M. catarrhalis (both 0.06 μg/ml) and for H. influenzae(both 0.03 μg/ml) were independent of β-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies.

scholarly journals Curcumin Analogues as a Potential Drug against Antibiotic Resistant Protein, β-Lactamases and L, D-Transpeptidases Involved in Toxin Secretion in Salmonella typhi: A Computational Approach

2021 ◽  
Vol 2 (1) ◽  
pp. 77-100
Author(s):  
Tanzina Akter ◽  
Mahim Chakma ◽  
Afsana Yeasmin Tanzina ◽  
Meheadi Hasan Rumi ◽  
Mst. Sharmin Sultana Shimu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Typhoid Fever ◽  
Homology Modeling ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Drug Candidate ◽  
In Vivo Experiments ◽  
Curcumin Analogs

Typhoid fever caused by the bacteria Salmonella typhi gained resistance through multidrug-resistant S. typhi strains. One of the reasons behind β-lactam antibiotic resistance is -lactamase. L, D-Transpeptidases is responsible for typhoid fever as it is involved in toxin release that results in typhoid fever in humans. A molecular modeling study of these targeted proteins was carried out by various methods, such as homology modeling, active site prediction, prediction of disease-causing regions, and by analyzing the potential inhibitory activities of curcumin analogs by targeting these proteins to overcome the antibiotic resistance. The five potent drug candidate compounds were identified to be natural ligands that can inhibit those enzymes compared to controls in our research. The binding affinity of both the Go-Y032 and NSC-43319 were found against β-lactamase was −7.8 Kcal/mol in AutoDock, whereas, in SwissDock, the binding energy was −8.15 and −8.04 Kcal/mol, respectively. On the other hand, the Cyclovalone and NSC-43319 had an equal energy of −7.60 Kcal/mol in AutoDock, whereas −7.90 and −8.01 Kcal/mol in SwissDock against L, D-Transpeptidases. After the identification of proteins, the determination of primary and secondary structures, as well as the gene producing area and homology modeling, was accomplished. The screened drug candidates were further evaluated in ADMET, and pharmacological properties along with positive drug-likeness properties were observed for these ligand molecules. However, further in vitro and in vivo experiments are required to validate these in silico data to develop novel therapeutics against antibiotic resistance.

scholarly journals Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) complexes with biacetyl-derived Schiff bases

2010 ◽  
Vol 75 (8) ◽  
pp. 1075-1084 ◽  
Author(s):  
Muhammad Imran ◽  
Mitu Liviu ◽  
Shoomaila Latif ◽  
Zaid Mahmood ◽  
Imtiaz Naimat ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Schiff Base ◽  
Metal Complexes ◽  
Schiff Bases ◽  
Bacterial Species ◽  
Electronic Spectroscopy ◽  
Salmonella Typhi ◽  
Schiff Base Ligands ◽  
No Donor

The condensation reactions of biacetyl with orthohydroxyaniline and 2-aminobenzoic acid to form bidendate NO donor Schiff bases were studied. The prepared Schiff base ligands were further utilized for the formation of metal chelates having the general formula [ML2.2H2O] where M = Co(II), Ni(II), Cu(II) and Zn(II) and L = HL1 and HL2. These new compounds were characterized by conductance measurements, magnetic susceptibility measurements, elemental analysis, and IR, 1H-NMR and electronic spectroscopy. Both Schiff base ligands were found to have a mono-anionic bidentate nature and octahedral geometry was assigned to all metal complexes. All the complexes contained coordinated water which was lost at 141-160 ?C. These compounds were also screened for their in-vitro antibacterial activity against four bacterial species, namely; Escherichia coli, Staphylococcus aureus, Salmonella typhi and Bacillus subtillis. The metal complexes were found to have greater antibacterial activity than the uncomplexed Schiff base ligands.

scholarly journals In Vitro and In Vivo Activities of PD 0305970 and PD 0326448, New Bacterial Gyrase/Topoisomerase Inhibitors with Potent Antibacterial Activities versus Multidrug-Resistant Gram-Positive and Fastidious Organism Groups

2007 ◽  
Vol 51 (4) ◽  
pp. 1191-1201 ◽  
Author(s):  
Michael D. Huband ◽  
Michael A. Cohen ◽  
Margaret Zurack ◽  
Debra L. Hanna ◽  
Laura A. Skerlos ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Topoisomerase Inhibitors ◽  
Gram Positive ◽  
Resistant Mutants

ABSTRACT PD 0305970 and PD 0326448 are new bacterial gyrase and topoisomerase inhibitors (quinazoline-2,4-diones) that possess outstanding in vitro and in vivo activities against a wide spectrum of bacterial species including quinolone- and multidrug-resistant gram-positive and fastidious organism groups. The respective MICs (μg/ml) for PD 0305970 capable of inhibiting ≥90% of bacterial strains tested ranged from 0.125 to 0.5 versus staphylococci, 0.03 to 0.06 versus streptococci, 0.25 to 2 versus enterococci, and 0.25 to 0.5 versus Moraxella catarrhalis, Haemophilus influenzae, Listeria monocytogenes, Legionella pneumophila, and Neisseria spp. PD 0326448 MIC90s were generally twofold higher versus these same organism groups. Comparative quinolone MIC90 values were 4- to 512-fold higher than those of PD 0305970. In testing for frequency of resistance, PD 0305970 and levofloxacin showed low levels of development of spontaneous resistant mutants versus both Staphylococcus aureus and Streptococcus pneumoniae. Unlike quinolones, which target primarily gyrA and parC, analysis of resistant mutants in S. pneumoniae indicates that the likely targets of PD 0305970 are gyrB and parE. PD 0305970 demonstrated rapid bactericidal activity by in vitro time-kill testing versus streptococci. This bactericidal activity carried over to in vivo testing, where PD 0305970 and PD 0326448 displayed outstanding Streptococcus pyogenes 50% protective doses (PD50s) (oral dosing) of 0.7 and 3.6 mg/kg, respectively (ciprofloxacin and levofloxacin PD50s were >100 and 17.7 mg/kg, respectively). PD 0305970 was also potent in a pneumococcal pneumonia mouse infection model (PD50 = 3.2 mg/kg) and was 22-fold more potent than levofloxacin.

scholarly journals The Role of Iron and Siderophores in Infection, and the Development of Siderophore Antibiotics

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S529-S537 ◽  
Author(s):  
Malcom G P Page
Keyword(s):  
Outer Membrane ◽  
Pathogenic Bacteria ◽  
Phase 1 ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Membrane Receptors ◽  
Transport Systems ◽  
Resistant Bacteria

Abstract Iron is an essential nutrient for bacterial growth, replication, and metabolism. Humans store iron bound to various proteins such as hemoglobin, haptoglobin, transferrin, ferritin, and lactoferrin, limiting the availability of free iron for pathogenic bacteria. However, bacteria have developed various mechanisms to sequester or scavenge iron from the host environment. Iron can be taken up by means of active transport systems that consist of bacterial small molecule siderophores, outer membrane siderophore receptors, the TonB-ExbBD energy-transducing proteins coupling the outer and the inner membranes, and inner membrane transporters. Some bacteria also express outer membrane receptors for iron-binding proteins of the host and extract iron directly from these for uptake. Ultimately, iron is acquired and transported into the bacterial cytoplasm. The siderophores are small molecules produced and released by nearly all bacterial species and are classified according to the chemical nature of their iron-chelating group (ie, catechol, hydroxamate, α-hydroxyl-carboxylate, or mixed types). Siderophore-conjugated antibiotics that exploit such iron-transport systems are under development for the treatment of infections caused by gram-negative bacteria. Despite demonstrating high in vitro potency against pathogenic multidrug-resistant bacteria, further development of several candidates had stopped due to apparent adaptive resistance during exposure, lack of consistent in vivo efficacy, or emergence of side effects in the host. However, cefiderocol, with an optimized structure, has advanced and has been investigated in phase 1 to 3 clinical trials. This article discusses the mechanisms implicated in iron uptake and the challenges associated with the design and utilization of siderophore-mimicking antibiotics.

scholarly journals Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914

2015 ◽  
Vol 290 (34) ◽  
pp. 20984-20994 ◽  
Author(s):  
Gunther Kern ◽  
Tiffany Palmer ◽  
David E. Ehmann ◽  
Adam B. Shapiro ◽  
Beth Andrews ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Type Ii ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Gram Negative

We characterized the inhibition of Neisseria gonorrhoeae type II topoisomerases gyrase and topoisomerase IV by AZD0914 (AZD0914 will be henceforth known as ETX0914 (Entasis Therapeutics)), a novel spiropyrimidinetrione antibacterial compound that is currently in clinical trials for treatment of drug-resistant gonorrhea. AZD0914 has potent bactericidal activity against N. gonorrhoeae, including multidrug-resistant strains and key Gram-positive, fastidious Gram-negative, atypical, and anaerobic bacterial species (Huband, M. D., Bradford, P. A., Otterson, L. G., Basrab, G. S., Giacobe, R. A., Patey, S. A., Kutschke, A. C., Johnstone, M. R., Potter, M. E., Miller, P. F., and Mueller, J. P. (2014) In Vitro Antibacterial Activity of AZD0914: A New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-positive, Fastidious Gram-negative, and Atypical Bacteria. Antimicrob. Agents Chemother. 59, 467–474). AZD0914 inhibited DNA biosynthesis preferentially to other macromolecules in Escherichia coli and induced the SOS response to DNA damage in E. coli. AZD0914 stabilized the enzyme-DNA cleaved complex for N. gonorrhoeae gyrase and topoisomerase IV. The potency of AZD0914 for inhibition of supercoiling and the stabilization of cleaved complex by N. gonorrhoeae gyrase increased in a fluoroquinolone-resistant mutant enzyme. When a mutation, conferring mild resistance to AZD0914, was present in the fluoroquinolone-resistant mutant, the potency of ciprofloxacin for inhibition of supercoiling and stabilization of cleaved complex was increased greater than 20-fold. In contrast to ciprofloxacin, religation of the cleaved DNA did not occur in the presence of AZD0914 upon removal of magnesium from the DNA-gyrase-inhibitor complex. AZD0914 had relatively low potency for inhibition of human type II topoisomerases α and β.

scholarly journals In Vitro Activities of a Novel Nanoemulsion against Burkholderia and Other Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species

2008 ◽  
Vol 53 (1) ◽  
pp. 249-255 ◽  
Author(s):  
John J. LiPuma ◽  
Sivaprakash Rathinavelu ◽  
Bridget K. Foster ◽  
Jordan C. Keoleian ◽  
Paul E. Makidon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Burkholderia Cepacia ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Opportunistic Pathogens ◽  
Oil In Water ◽  
Distinct Strain ◽  
Treatment Of Infection

ABSTRACT Respiratory tract infection, most often involving opportunistic bacterial species with broad-spectrum antibiotic resistance, is the primary cause of death in persons with cystic fibrosis (CF). Species within the Burkholderia cepacia complex are especially problematic in this patient population. We investigated a novel surfactant-stabilized oil-in-water nanoemulsion (NB-401) for activity against 150 bacterial isolates recovered primarily from CF respiratory tract specimens. These specimens included 75 Burkholderia isolates and 75 isolates belonging to other CF-relevant species including Pseudomonas, Achromobacter, Pandoraea, Ralstonia, Stenotrophomonas, and Acinetobacter. Nearly one-third of the isolates were multidrug resistant, and 20 (13%) were panresistant based on standard antibiotic testing. All isolates belonging to the same species were genotyped to ensure that each isolate was a distinct strain. The MIC90 of NB-401 was 125 μg/ml. We found no decrease in activity against multidrug-resistant or panresistant strains. MBC testing showed no evidence of tolerance to NB-401. We investigated the activity of NB-401 against a subset of strains grown as a biofilm and against planktonic strains in the presence of CF sputum. Although the activity of NB-401 was decreased under both conditions, the nanoemulsion remained bactericidal for all strains tested. These results support NB-401's potential role as a novel antimicrobial agent for the treatment of infection due to CF-related opportunistic pathogens.

scholarly journals Bacteriophage Structure, Classification, Assembly and Phage Therapy

2021 ◽  
Vol 18 (2) ◽  
pp. 239-250
Author(s):  
Nabanita Giri
Keyword(s):  
Bacterial Infections ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
The Other ◽  
Basic Knowledge ◽  
New Antibiotics ◽  
Associated Proteins ◽  
Conventional Antibiotics ◽  
And Function ◽  
Structure Configuration

Current emergence of multidrug resistance and limitations in the development of the new antibiotics has proposed the problem of treating bacterial infections more challenging. This scenario may lead to the fear of failure in treating the multidrug resistant (MDR) bacterial infections and fuelled the uses of bacteriophages as an alternative of the conventional antibiotics in the post antibiotic era.So it is very much essential to know about the details of phage life cycle, assembly of phage complete structure, configuration and function of phage associated proteins etc. Although phages have been discovered a century ego, detailed study about lytic phages are gaining more interest in global fight against MDR bacterial species. This review has highlighted the basic knowledge of bacteriophage with the past and present scenario of several clinical studies targeting the MDR bacterial species. On the other hand it also discussed about the other uses of phages except human clinical trials.

scholarly journals Antimicrobial screening of selected flora of Pakistan

2011 ◽  
Vol 63 (3) ◽  
pp. 691-695 ◽  
Author(s):  
M. Zia-Ul-Haq ◽  
Mansoor Ahmad ◽  
M Mehjabeen ◽  
Noor Jehan ◽  
Shakeel Ahmad ◽  
...  
Keyword(s):  
Nigella Sativa ◽  
Micrococcus Luteus ◽  
Bacterial Species ◽  
Macrophomina Phaseolina ◽  
Salmonella Typhi ◽  
Lepidium Sativum ◽  
Significant Activity ◽  
Fungal Strains ◽  
Antibacterial And Antifungal Activities

Ethanolic extracts of Ferula assafoetida resin, Grewia asiatica leaves, Ipomoea hederacea seeds, Lepidium sativum seeds, Nigella sativa seeds and Terminalia chebula fruits were tested in vitro for their antibacterial and antifungal activities. The antibacterial study performed against eight bacterial species viz., Escherichia coli, Citrobacter, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Micrococcus luteus, Proteus mirabilis and Bacillus subtilis indicated that the investigated plants have potent activity against all the tested microorganisms. The antifungal activity of these extracts was performed against nine fungal strains, viz., Aspergillus parasiticus, Aspergillus niger, Yersinia aldovae, Candida albicans, Aspergillus effusus, Fusarium solani, Macrophomina phaseolina, Saccharomyces cerevisiae and Trichophyton rubrum. The extracts showed moderate as well as significant activity against the different fungal strains.

scholarly journals Antibacterial Activities of Five Medicinal Plants in Ethiopia against Some Human and Animal Pathogens

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Gebremedhin Romha ◽  
Birhanu Admasu ◽  
Tsegaye Hiwot Gebrekidan ◽  
Hailelule Aleme ◽  
Gebreyohans Gebru
Keyword(s):  
Medicinal Plants ◽  
Bacterial Species ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Resistant Bacteria ◽  
Traditional Medicines ◽  
Animal Pathogens ◽  
Significant Difference

Objective. To evaluate thein vitroantibacterial activities of five plant extracts which have been used as traditional medicines by local healers against three multidrug resistant bacteria, namely,Staphylococcus aureus,Escherichia coli, andPseudomonas aeruginosa.Results. The highest mean zone of inhibition (4.66 mm) was recorded from methanol extract ofCalpurnia aurea(Ait.) Benth. at a concentration of 200 mg/ml againstS. aureus, followed byCroton macrostachyusDel. (4.43 mm) at the same dose and solvent for the same bacterial species, while methanol and chloroform extracts ofE. bruceiSchwein. did not inhibit growth of any bacterial species. The lowest value (100 μg/ml) of minimum inhibitory concentration (MIC) was observed from both methanol and chloroform extracts ofC. aurea(Ait.) Benth. against all the three bacteria. The results of the positive control had no statistically significant difference (P>0.05) when compared with crude extracts ofC. aurea(Ait.) Benth. at concentration of 200 mg/ml againstS. aureus.Conclusion. The results of the present study support the traditional uses of these medicinal plants by the local healers. ExceptErythrina bruceiSchwein., all the plants investigated in this study exhibited antibacterial activities against the test bacterial species. Further researches are needed to be conducted to evaluate efficacy of these medicinal plant species on other microbes in different agroecological settings and their safety levels as well as their phytochemical compositions.

Sign in / Sign up

Export Citation Format

Share Document