Emerging Resistance to Antimicrobial Agents in Gram-Positive Bacteria

ABSTRACTLeguminous plants establish symbiosis with nitrogen-fixing alpha- and betaproteobacteria, collectively called rhizobia, which provide combined nitrogen to support plant growth. Members of the inverted repeat-lacking clade of legumes impose terminal differentiation on their endosymbiotic bacterium partners with the help of the nodule-specific cysteine-rich (NCR) peptide family composed of close to 600 members. Among the few tested NCR peptides, cationic ones had antirhizobial activity measured by reduction or elimination of the CFU and uptake of the membrane-impermeable dye propidium iodide. Here, the antimicrobial spectrum of two of these peptides, NCR247 and NCR335, was investigated, and their effect on the transcriptome of the natural targetSinorhizobium melilotiwas characterized. Both peptides were able to kill quickly a wide range of Gram-negative and Gram-positive bacteria; however, their spectra were only partially overlapping, and differences were found also in their efficacy on given strains, indicating that the actions of NCR247 and NCR335 might be similar though not identical. Treatment ofS. meliloticultures with either peptide resulted in a quick downregulation of genes involved in basic cellular functions, such as transcription-translation and energy production, as well as upregulation of genes involved in stress and oxidative stress responses and membrane transport. Similar changes provoked mainly in Gram-positive bacteria by antimicrobial agents were coupled with the destruction of membrane potential, indicating that it might also be a common step in the bactericidal actions of NCR247 and NCR335.

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Construction of Leaderless-Bacteriocin-Producing Bacteriophage Targeting E. coli and Neighboring Gram-Positive Pathogens

Microbiology Spectrum ◽

10.1128/spectrum.00141-21 ◽

2021 ◽

Author(s):

Yoshimitsu Masuda ◽

Shun Kawabata ◽

Tatsuya Uedoi ◽

Ken-ichi Honjoh ◽

Takahisa Miyamoto

Keyword(s):

Antimicrobial Agents ◽

Host Strain ◽

Phage Resistance ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria ◽

T7 Phage

We demonstrated that we could combine LLB and phage to construct promising novel antimicrobial agents, LLB-phage. The first LLB-phage, lnqQ -T7 phage, can control the growth of both the Gram-negative host strain and neighboring Gram-positive bacteria while preventing the emergence of phage resistance in the host strain.

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Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

Microorganisms ◽

10.3390/microorganisms8020191 ◽

2020 ◽

Vol 8 (2) ◽

pp. 191 ◽

Cited By ~ 4

Author(s):

Despoina Koulenti ◽

Elena Xu ◽

Andrew Song ◽

Isaac Yin Sum Mok ◽

Drosos E. Karageorgopoulos ◽

...

Keyword(s):

Safety Profile ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

Current Treatment ◽

Multi Drug Resistance ◽

Gram Positive ◽

Treatment Regimens ◽

Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

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In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01715-19 ◽

2019 ◽

Vol 64 (3) ◽

Cited By ~ 1

Author(s):

Ian Morrissey ◽

Stephen Hawser ◽

Sibylle H. Lob ◽

James A. Karlowsky ◽

Matteo Bassetti ◽

...

Keyword(s):

Antimicrobial Agents ◽

Clinical Isolates ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria ◽

Microdilution Method ◽

Clinical Laboratories ◽

Broth Microdilution Method ◽

Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

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Resistance of anaerobic Gram-positive bacteria to antimicrobial agents

Reviews in Medical Microbiology ◽

10.1097/00013542-199712001-00043 ◽

1997 ◽

Vol 8 ◽

pp. S81

Author(s):

Ludmila Boyanova

Keyword(s):

Antimicrobial Agents ◽

Gram Positive ◽

Gram Positive Bacteria

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Combination of Pantothenamides with Vanin Inhibitors as a Novel Antibiotic Strategy against Gram-Positive Bacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00603-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 4794-4800 ◽

Cited By ~ 20

Author(s):

Patrick A. M. Jansen ◽

Pedro H. H. Hermkens ◽

Patrick L. J. M. Zeeuwen ◽

Peter N. M. Botman ◽

Richard H. Blaauw ◽

...

Keyword(s):

Antimicrobial Agents ◽

Acid Synthesis ◽

Spectrometric Analysis ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria ◽

New Compounds ◽

Emergence Of Resistance ◽

Hydrolysis Of

ABSTRACTThe emergence of resistance against current antibiotics calls for the development of new compounds to treat infectious diseases. Synthetic pantothenamides are pantothenate analogs that possess broad-spectrum antibacterial activityin vitroin minimal media. Pantothenamides were shown to be substrates of the bacterial coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and interference with fatty acid synthesis. In spite of their potential use and selectivity for bacterial metabolic routes, these compounds have never made it to the clinic. In the present study, we show that pantothenamides are not active as antibiotics in the presence of serum, and we found that they were hydrolyzed by ubiquitous pantetheinases of the vanin family. To address this further, we synthesized a series of pantetheinase inhibitors based on a pantothenate scaffold that inhibited serum pantetheinase activity in the nanomolar range. Mass spectrometric analysis showed that addition of these pantetheinase inhibitors prevented hydrolysis of pantothenamides by serum. We found that combinations of these novel pantetheinase inhibitors and prototypic pantothenamides like N5-Pan and N7-Pan exerted antimicrobial activityin vitro, particularly against Gram-positive bacteria (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae, andStreptococcus pyogenes) even in the presence of serum. These results indicate that pantothenamides, when protected against degradation by host pantetheinases, are potentially useful antimicrobial agents.

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Mixtures of Scutellaria baicalensis and Glycyrrhiza L. Extracts as Antibacterial and Antiviral Agents in Active Coatings

Coatings ◽

10.3390/coatings11121438 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1438

Author(s):

Magdalena Ordon ◽

Paweł Nawrotek ◽

Xymena Stachurska ◽

Anna Schmidt ◽

Małgorzata Mizielińska

Keyword(s):

Synergistic Effect ◽

Pseudomonas Syringae ◽

Plant Extracts ◽

Antimicrobial Agents ◽

Antiviral Agents ◽

Scutellaria Baicalensis ◽

Bacterial Strains ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Highly Active

The aim of this study was to develop active packaging materials covered in active coatings (offering antibacterial and antiviral properties) that contain selected plant extracts. In addition, the synergistic effect of the active substances in these extracts was also analysed. The results of the study demonstrated that Scutellaria baicalensis and Glycyrrhiza L. extracts (two of six analysed plant extracts) were the most active agents against selected Gram-positive and Gram-negative bacterial strains. Additionally, the synergistic effect of S. baicalensis and Glycyrrhiza L. extracts was noted, meaning that the effect of these two plant extract mixtures on Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas syringae growth was higher than the activity of individual pure extracts. Mixtures of the extracts were introduced into the coating carrier. A polyethylene (PE) foil was then coated with active layers containing mixtures of S. baicalensis and Glycyrrhiza L. extracts as antimicrobial agents. The results of this research showed that all of the active coatings had a bacteriolytic effect on B. subtilis and a bacteriostatic effect on S. aureus cells. The coatings were found to be inactive against E. coli and P. syringae cells. This means that the coatings could be used as internal coatings to preserve food products against Gram-positive bacteria that may be responsible for food spoilage. The results of this study also demonstrated that the coatings were highly active against phage phi 6 phage particles, used as SARS-CoV-2 surrogate. This means that the coatings could be used as external coatings to limit the spread of SARS-CoV-2 and pathogenic Gram-positive bacteria via human hands.

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Synthesis, Antibacterial and Antifungal Properties of Cyclohexane Tosyloxyimine Derivative

Open Access Journal of Microbiology & Biotechnology ◽

10.23880/oajmb-16000150 ◽

2019 ◽

Vol 4 (3) ◽

pp. 1-4

Author(s):

Shoaib M

Keyword(s):

Antimicrobial Agents ◽

Sulfonyl Chloride ◽

Antimicrobial Properties ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Bacteria And Fungi ◽

Agar Well Diffusion Assay ◽

Antibacterial And Antifungal ◽

Candida Pseudotropicalis

Due to increasing antimicrobial resistance, functionally substituted cyclohexane derivatives are being explored as potential antimicrobial agents. Reaction of diethyl 4 - hydroxy - 6 - (hyd - roxyimino) - 4 - methyl - 2 - phenylcyclohexane - 1,3 - dicarboxylate with 4 - toluene sulfonyl chloride in boiling acetone in the presence of equimolar triethylamine resulted in formation of diethyl - 4 - hydroxy - 4 - methyl - 2 - phenyl - 6 - ((tosyloxy)imino) cyclohexane - 1,3 - dicarboxylate. The structure of novel compound was characterized by 1 H and 13 C NMR spectra and elemental analysis was performed. Agar well diffusion assay was used to screen novel compound against Gram - positive bacteria, Gram - negative bacteria and fungi. Test compound showed better antimicrobial properties against Gram - negative bac teria as compared to Gram - positive bacteria and fungi. Acinetobacter baumannii BDU - 32 was found to be most sensitive bacteria while Candida pseudotropicalis BDU MA88 was found to be most sensitive yeast.

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Redox-active cationic organoiron complex: a promising lead structure for developing antimicrobial agents with activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium

RSC Advances ◽

10.1039/c5ra16613f ◽

2015 ◽

Vol 5 (105) ◽

pp. 86421-86427 ◽

Cited By ~ 9

Author(s):

Alaa S. Abd-El-Aziz ◽

Christian Agatemor ◽

Nola Etkin ◽

David P. Overy ◽

Russell G. Kerr

Keyword(s):

Antimicrobial Agents ◽

Methicillin Resistant Staphylococcus Aureus ◽

Multidrug Resistant ◽

Gram Positive ◽

Lead Structure ◽

Gram Positive Bacteria ◽

Redox Active ◽

Vancomycin Resistant ◽

Organoiron Complexes ◽

Multidrug Resistant Strain

A redox-active, cationic organoiron complexes active against multidrug-resistant strain of Gram-positive bacteria is presented as a potential new lead structure for the design of antimicrobial agents.

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