scholarly journals Burkholderia Bacteria Produce Multiple Potentially Novel Molecules that Inhibit Carbapenem-Resistant Gram-Negative Bacterial Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 147
Author(s):  
Eliza Depoorter ◽  
Evelien De Canck ◽  
Tom Coenye ◽  
Peter Vandamme
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Pathogens ◽  
Sensu Stricto ◽  
Bioactive Molecules ◽  
Molecular Formula ◽  
The Novel ◽  
Uv Spectrum ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Global Threat

Antimicrobial resistance in Gram-negative pathogens represents a global threat to human health. This study determines the antimicrobial potential of a taxonomically and geographically diverse collection of 263 Burkholderia (sensu lato) isolates and applies natural product dereplication strategies to identify potentially novel molecules. Antimicrobial activity is almost exclusively present in Burkholderia sensu stricto bacteria and rarely observed in the novel genera Paraburkholderia, Caballeronia, Robbsia, Trinickia, and Mycetohabitans. Fourteen isolates show a unique spectrum of antimicrobial activity and inhibited carbapenem-resistant Gram-negative bacterial pathogens. Dereplication of the molecules present in crude spent agar extracts identifies 42 specialized metabolites, 19 of which represented potentially novel molecules. The known identified Burkholderia metabolites include toxoflavin, reumycin, pyrrolnitrin, enacyloxin, bactobolin, cepacidin, ditropolonyl sulfide, and antibiotics BN-227-F and SF 2420B, as well as the siderophores ornibactin, pyochelin, and cepabactin. Following semipreparative fractionation and activity testing, a total of five potentially novel molecules are detected in active fractions. Given the molecular formula and UV spectrum, two of those putative novel molecules are likely related to bactobolins, and another is likely related to enacyloxins. The results from this study confirm and extend the observation that Burkholderia bacteria present exciting opportunities for the discovery of potentially novel bioactive molecules.

scholarly journals Genome-Wide Identification of Carbapenem-Resistant Gram- Negative Bacterial (CR-GNB) Isolates Retrieved From Hospitalized Patients in Bihar, India

2021 ◽  
Author(s):  
Namrata Kumari ◽  
Mukesh Kumar ◽  
Amit Katiyar ◽  
Abhay Kumar ◽  
Pallavi Priya ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Carbapenem Resistance ◽  
Cross Sectional Study ◽  
Clinical Isolates ◽  
Cross Sectional ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Genome Wide ◽  
Synergy Test ◽  
Global Threat

Abstract Carbapenemase-producing clinical isolates are becoming more common over the world, posing a severe public health danger, particularly in developing nations like India. Carbapenem-resistant Gram-negative bacterial (CR-GNB) infection has become a fast-expending global threat with limited antibiotic choice and significant mortality. The aim of this study was to highlight the carbapenem-resistance among clinical isolates of hospital admitted patients in Bihar, India. A cross-sectional study was conducted with 101 clinical isolates of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. All GNB isolates were tested for their antimicrobial susceptibility using double disc synergy test / modified hodge test (DDST/MHT) and subsequently confirmed carbapenemase-producing isolates were evaluated for carbapenem-resistance genes using whole-genome sequencing (genotypically) method. The overall percentage of carbapenem-resistance among GNB was (17/101) 16.83%. The AMR analysis demonstrates a significantly high prevalence of blaCTX−M followed by blaSHV, blaTEM, blaOXA and blaNDM β-lactams carbapenem-resistance genes among clinical isolates of GNB. Co-occurrence of carbapenemase-encoding genes with blaNDM was found in 70.6% of carbapenemase-producing isolates. Our study highlights the mechanism of carbapenem-resistance to curb the overwhelming threat posed by emergence of drug-resistance in India.

scholarly journals Using Molecular Diagnostics to Develop Therapeutic Strategies for Carbapenem-Resistant Gram-Negative Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Fred C. Tenover
Keyword(s):  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Therapeutic Strategies ◽  
Beta Lactam ◽  
Gram Negative ◽  
Molecular Tests ◽  
Negative Results ◽  
Carbapenem Resistant ◽  
Class B ◽  
Global Threat

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly is critical. Using molecular tests to detect and differentiate carbapenem-resistance genes (CRG) in bacterial isolates provides fast and actionable results, but utilization of these tests globally appears to be low. Detecting CRG directly in positive blood culture bottles or in syndromic panels coupled with bacterial identification are helpful when results are positive, however, even negative results can provide guidance for anti-infective therapy for key organism-drug combinations when linked to local epidemiology. This perspective will focus on the reluctance of laboratories to use molecular tests as aids to developing therapeutic strategies for infections caused by carbapenem-resistant organisms and how to overcome that reluctance.

Activity of free fatty acids-rich non-polar fractions from fruits of Capsicum chinense var. Criolla and Jaguar

2019 ◽  
Vol 66 (3-4) ◽  
pp. 220-226
Author(s):  
J. Efrain Ramirez-Benitez ◽  
Ibis Vargas Paredes ◽  
Luis F. Cuevas Glory ◽  
Enrique Sauri Duch ◽  
Victor M. Moo Huchin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Staphylococcus Epidermidis ◽  
Bioactive Molecules ◽  
Biological Functions ◽  
Capsicum Chinense ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Plant Essential Oils ◽  
Unripe Fruits

Plant-essential oils have been considered as an important source of bioactive molecules like antimicrobials, analgesics, anti-inflammatory and anti-carcinogen agents. Biological functions of plant extracts from the genus Capsicum are unknown. In the present work, non-polar fractions of ripe and unripe fruits of Capsicum chinense Jacq. Cultivar (cv.) Jaguar and Criollo were obtained by hexane-batch extraction and tested for antimicrobial activity against Gram-negative bacterial strain Escherichia coli (ATCC 25922), Gram-positive bacterial strains Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 12228), and yeast Candida albicans (ATCC 90028). Non-polar fractions from ripe fruits for both cv. exhibited greater antimicrobial activity compared to unripe fruits. Implication of numbered FFA’s on observed antimicrobial activity are discussed.

scholarly journals Investigation of the Antimicrobial Activity of Some Streptomyces spp. Isolated from Nineveh Province

2010 ◽  
Vol 4 (2) ◽  
pp. 24-32
Author(s):  
M. B. I. Kassim ◽  
S. S. Eleya
Keyword(s):  
Antimicrobial Activity ◽  
Active Compound ◽  
Bioactive Compound ◽  
Gram Negative Bacteria ◽  
High Antimicrobial Activity ◽  
Biochemical Tests ◽  
Uv Spectrum ◽  
Gram Negative ◽  
Streptomyces Spp ◽  
Streptomyces Lavendulae

Atotal of 62 different Streptomyces isolates were recovered from 17 samples of soil collected from different sites of Nineveh Province. Only 23 isolates showed activity against test Gram-positive and Gram-negative bacteria. One isolate showed high antimicrobial activity against Staphylococcus aureus, was selected and identified as Streptomyces lavendulae on the bases of microscopic, morphologic, biochemical tests and its sensitivity to some antibiotics. The bioactive compound produced by S. lavendulae was isolated on TLC plate (Rf 0.85). The UV spectrum of the active compound in methanol showed one peak at 280 nm. From these data it could be concluded that the active compound probably belongs to macrolide antibiotics group.

scholarly journals Mutasynthetic Production and Antimicrobial Characterization of Darobactin Analogs

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Nils Böhringer ◽  
Robert Green ◽  
Yang Liu ◽  
Ute Mettal ◽  
Michael Marner ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Heterologous Expression ◽  
Bacterial Pathogens ◽  
Therapeutic Options ◽  
The Novel ◽  
Proof Of Concept ◽  
Gram Negative ◽  
Pharmacokinetic Properties

Therapeutic options to combat Gram-negative bacterial pathogens are dwindling with increasing antibiotic resistance. This study presents a proof of concept for the heterologous-expression approach to expand on the novel antibiotic class of darobactins and to generate analogs with different activities and pharmacokinetic properties.

scholarly journals Therapeutic Effect and Mechanisms of the Novel Monosulfactam 0073

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Ying Sun ◽  
Xueyuan Liao ◽  
Zhigang Huang ◽  
Yaliu Xie ◽  
Yanbin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Serial Passage ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Infection Model ◽  
The Novel ◽  
Gram Negative ◽  
Content Type

ABSTRACT This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria in vitro and in vivo and to characterize the mechanisms underlying 0073 activity. The in vitro activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acute toxicity assays. Murine thigh infection and pneumonia models were employed to define in vivo efficacy. A penicillin-binding protein (PBP) competition assay and confocal microscopy were conducted. The inhibitory action of 0073 against β-lactamases was evaluated by the half-maximal inhibitory concentration (IC50), and resistance development was evaluated via serial passage. The monosulfactam 0073 showed promising antimicrobial activity against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates producing metallo-β-lactamases (MBLs) and serine β-lactamases. In preliminary experiments, compound 0073 exhibited safety both in vitro and in vivo. In the murine thigh infection model and the pneumonia models in which infection was induced by P. aeruginosa and Klebsiella pneumoniae, 0073 significantly reduced the bacterial burden. Compound 0073 targeted several PBPs and exerted inhibitory effects against some serine β-lactamases. Finally, 0073 showed a reduced propensity for resistance selection compared with that of aztreonam. The novel monosulfactam 0073 exhibited increased activity against β-lactamase-producing Gram-negative organisms compared with the activity of aztreonam and showed good safety profiles both in vitro and in vivo. The underlying mechanisms may be attributed to the affinity of 0073 for several PBPs and its inhibitory activity against some serine β-lactamases. These data indicate that 0073 represents a potential treatment for infections caused by β-lactamase-producing multidrug-resistant bacteria.

scholarly journals Antimicrobial activity of the novel polymyxin derivative NAB739 tested against Gram-negative pathogens

2012 ◽  
Vol 68 (3) ◽  
pp. 636-639 ◽  
Author(s):  
M. Vaara ◽  
H. S. Sader ◽  
P. R. Rhomberg ◽  
R. N. Jones ◽  
T. Vaara
Keyword(s):  
Antimicrobial Activity ◽  
The Novel ◽  
Gram Negative

scholarly journals Draft Genome Sequence of a Multidrug-Resistant Klebsiella pneumoniae Strain Isolated from King Abdullah Medical City, Makkah, Saudi Arabia

2016 ◽  
Vol 4 (3) ◽  
Author(s):  
Rayd Algowaihi ◽  
Sami Ashgar ◽  
Bashir Sirag ◽  
Sheerin Shalam ◽  
Anmar Nassir ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Draft Genome Sequence ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Medical City ◽  
Global Threat

Multidrug-resistant (MDR) Gram-negative infections represent a growing problem and a serious global threat. Carbapenem-resistant Klebsiella pneumoniae is perhaps cause the most difficult infection to treat and is associated with increased morbidity and mortality. Here, we report the draft genome sequence of an MDR K. pneumoniae strain isolated from Makkah, Saudi Arabia.

scholarly journals Nisin- and ripcin-derived hybrid lanthipeptides display selective antimicrobial activity against Staphylococcus aureus

2021 ◽  
Author(s):  
Xinghong Zhao ◽  
Oscar P. Kuipers
Keyword(s):  
Antimicrobial Activity ◽  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Disulfide Bond ◽  
Bacterial Pathogens ◽  
Cell Wall Synthesis ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Lipid Ii ◽  
Selective Antimicrobial Activity

Lanthipeptides are (methyl)lanthionine ring-containing ribosomally synthesized and post-translationally modified peptides (RiPPs). Many lanthipeptides show strong antimicrobial activity against bacterial pathogens, including antibiotic-resistant bacterial pathogens. The group of disulfide bond-containing antimicrobial peptides (AMPs) is well known in nature and forms a rich source of templates for the production of novel peptides with corresponding (methyl)lanthionine analogues instead of disulfides. Here, we show that novel macrocyclic lanthipeptides (termed thanacin and ripcin) can be synthesized using the known antimicrobials thanatin and rip-thanatin as templates. Notably, the synthesized nisin(1-20)-ripcin hybrid lanthipeptides (ripcin B-G) showed selective antimicrobial activity against S. aureus, including an antibiotic-resistant MRSA strain. Interestingly, ripcin B-G, which are hybrid peptides of nisin(1-20) and ripcin, respectively, that are each inactive against Gram-negative pathogens, showed substantial antimicrobial activity against the tested Gram-negative pathogens. Moreover, ripcin B-G was highly resistant against the nisin resistance protein (NSR; a protease could cleave nisin and strongly reduce its activity ), opposed to nisin itself. Mode of action studies show that ripcin C exerts its antimicrobial activity against Gram-positive pathogens by binding to the cell wall synthesis precursor lipid II and thereafter arrests cell growth. In addition, ripcin C exerts its antimicrobial activity against Gram-negative pathogens by binding to LPS and the cell wall synthesis precursor lipid II. This study provides an example of converting disulfide bond-based AMPs into (methyl)lanthionine-based macrocyclic hybrid lanthipeptides and can yield antimicrobial peptides with selective antimicrobial activity against S. aureus.

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF 3-FORMYL INDOLE BASED SCHIFF BASES

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Singh Gurvinder ◽  
Singh Prabhsimran ◽  
Dhawan R. K.
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Analysis ◽  
Schiff Bases ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Fungal Strain ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Gram Negative ◽  
E Coli

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The  standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.

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