scholarly journals Heterologous Expression of the Marine-Derived Quorum Quenching Enzyme MomL Can Expand the Antibacterial Spectrum of Bacillus brevis

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 128 ◽  
Author(s):  
Jingjing Zhang ◽  
Jiayi Wang ◽  
Tao Feng ◽  
Rui Du ◽  
Xiaorong Tian ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Bacterial Pathogens ◽  
Quorum Quenching ◽  
Plant Diseases ◽  
Signal Molecules ◽  
Bacterial Disease ◽  
Gram Positive ◽  
Bacillus Brevis ◽  
Gram Negative ◽  
Antibacterial Spectrum

Quorum sensing (QS) is closely associated with the production of multiple virulence factors in bacterial pathogens. N-acyl homoserine lactones (AHLs) are important QS signal molecules that modulate the virulence of gram-negative pathogenic bacteria. Enzymatic degradation of AHLs to interrupt QS, termed quorum quenching (QQ), has been considered a novel strategy for reduction of pathogenicity and prevention of bacterial disease. However, the low expression levels of QQ proteins in the original host bacteria has affected the applications of these proteins. Previously, we identified a novel marine QQ enzyme, named MomL, with high activity and promising biocontrol function. In this study, we linked the target fragment momL to pNCMO2, which provided a basis for the first heterologous expression of MomL in the antifungal and anti-gram-positive-bacteria biocontrol strain Bacillus brevis, and obtaining the recombinant strain named BbMomL. The QQ activity of BbMomL was confirmed using a series of bioassays. BbMomL could not only degrade the exogenous signal molecule C6-HSL, but also the AHL signal molecules produced by the gram-negative pathogens Pectobacterium carotovorum subsp. carotovorum (Pcc) and Pseudomonas aeruginosa PAO1. In addition, BbMomL significantly reduced the secretion of pathogenic factors and the pathogenicity of Pcc and P. aeruginosa PAO1. We tested the biocontrol function of BbMomL for prevention of plant diseases in vitro. The result indicates that BbMomL has a broad antibacterial spectrum. Compared with wild-type B. brevis, BbMomL not only inhibited fungi and gram-positive bacterial pathogens but also considerably inhibited gram-negative bacterial pathogens. Moreover, the Bacillus brevis expression system has good application prospects and is an ideal host for expression and secretion of foreign proteins.

Silica Supported Synthesis and Quorum Quenching Ability of Isoxazolones Against Both Gram Positive and Gram Negative Bacterial Pathogens

2021 ◽  
Vol 6 (42) ◽  
pp. 11718-11728
Author(s):  
Hari K. Kadam ◽  
Komal Salkar ◽  
Akshata P. Naik ◽  
Milind M. Naik ◽  
Lalitprabha N. Salgaonkar ◽  
...  
Keyword(s):  
Bacterial Pathogens ◽  
Quorum Quenching ◽  
Gram Positive ◽  
Gram Negative

scholarly journals A Quorum Quenching Bacterial Isolate Contains Multiple Substrate-Inducible Genes Conferring Degradation of Diffusible Signal Factor

2020 ◽  
Vol 86 (7) ◽  
Author(s):  
Huishan Wang ◽  
Lisheng Liao ◽  
Shaohua Chen ◽  
Lian-Hui Zhang
Keyword(s):  
Molecular Basis ◽  
Bacterial Isolate ◽  
Bacterial Pathogens ◽  
Quorum Quenching ◽  
Gram Negative ◽  
Content Type ◽  
Signal Degradation ◽  
Highly Active ◽  
Diffusible Signal Factor ◽  
Degradation Activity

ABSTRACT Quorum quenching, which disrupts quorum sensing (QS) by either degradation of QS signals or interference of signal generation or perception, is a promising strategy for the prevention and control of QS-mediated bacterial infections. Diffusible signal factor (DSF) is widely conserved in many Gram-negative bacterial pathogens. In this study, we developed an efficient method for screening of highly active DSF degradation microorganisms. Among them, Pseudomonas sp. strain HS-18 showed a superior DSF degradation activity. Bioinformatics and genetic analyses showed that at least 4 genes, designated digA to digD, encoding fatty acyl coenzyme A ligase homologues, are responsible for DSF signal degradation. Interestingly, all 4 dig genes were induced by exogenous DSF, with digA being the most significantly induced. Expression of the dig genes in Xanthomonas campestris pv. campestris markedly reduced the accumulation of endogenous DSF, decreased production of virulence factors, and attenuated bacterial virulence on host plants. Similarly, application of strain HS-18 as a biocontrol agent could substantially reduce the disease severity caused by X. campestris pv. campestris. These results unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful genes and biocontrol agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens. IMPORTANCE Diffusible signal factor (DSF) represents a family of widely conserved quorum sensing signals involved in the regulation of virulence factor production in many Gram-negative bacterial pathogens. In this study, we developed a novel and efficient method for screening highly active DSF degradation microorganisms. With this method, we identified a bacterial isolate, Pseudomonas sp. strain HS-18, with a superb DSF degradation activity. We further found that strain HS-18 contains 4 genes responsible for DSF signal degradation, and significantly, these were induced by exogenous DSF molecules. These findings unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful methods, genes, and agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens.

scholarly journals Bacterial Cellulose Containing Combinations of Antimicrobial Peptides with Various QQ Enzymes as a Prototype of an “Enhanced Antibacterial” Dressing: In Silico and In Vitro Data

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1155
Author(s):  
Aysel Aslanli ◽  
Ilya Lyagin ◽  
Nikolay Stepanov ◽  
Denis Presnov ◽  
Elena Efremenko
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Cellulose ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Penicillin Acylase ◽  
Signal Molecules ◽  
Bacterial Cells ◽  
Gram Positive ◽  
Gram Negative

To improve the action of already in use antibiotics or new antimicrobial agents against different bacteria, the development of effective combinations of antimicrobial peptides (AMPs) with enzymes that can quench the quorum (QQ) sensing of bacterial cells was undertaken. Enzymes hydrolyzing N-acyl homoserine lactones (AHLs) and peptides that are signal molecules of Gram-negative and Gram-positive bacterial cells, respectively, were estimated as “partners” for antibiotics and antimicrobial peptides in newly designed antimicrobial–enzymatic combinations. The molecular docking of six antimicrobial agents to the surface of 10 different QQ enzyme molecules was simulated in silico. This made it possible to choose the best variants among the target combinations. Further, bacterial cellulose (BC) was applied as a carrier for uploading such combinations to generally compose prototypes of effective dressing materials with morphology, providing good absorbance. The in vitro analysis of antibacterial activity of prepared BC samples confirmed the significantly enhanced efficiency of the action of AMPs (including polymyxin B and colistin, which are antibiotics of last resort) in combination with AHL-hydrolyzing enzymes (penicillin acylase and His6-tagged organophosphorus hydrolase) against both Gram-negative and Gram-positive cells.

scholarly journals Different Modes of Action of Naphthyridones in Gram-Positive and Gram-Negative Bacteria

2006 ◽  
Vol 50 (1) ◽  
pp. 385-387 ◽  
Author(s):  
Ed T. Buurman ◽  
Kenneth D. Johnson ◽  
Roxanne K. Kelly ◽  
Kathy MacCormack
Keyword(s):  
Escherichia Coli ◽  
Haemophilus Influenzae ◽  
Mode Of Action ◽  
Bacterial Pathogens ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Modes Of Action

ABSTRACT Naphthyridones that were recently described as a class of translation inhibitors in gram-positive bacteria mediate their mode of action via GyrA in Haemophilus influenzae and Escherichia coli. These are the first examples of compounds in which modes of action in different bacterial pathogens are mediated through widely different targets.

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.

Combination Therapy for Bacterial Pathogens: Naturally Derived Antimicrobial Drugs Augmented with Ulva lactuca Extract

2021 ◽  
Vol 21 ◽  
Author(s):  
Nilushi Indika Bamunuarachchi ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Bacterial Pathogens ◽  
Dilution Method ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Hexane Extracts ◽  
Conventional Antibiotics

Background: With the growing incidence of microbial pathogenesis, several alternative strategies have been developed. The number of treatments using naturally (e.g., plants, algae, fungi, bacteria, and animals) derived compounds has increased. Importantly, marine-derived products have become a promising and effective approach to combat the antibiotic resistance properties developed by bacterial pathogens. Furthermore, augmenting the sub-inhibitory concentration of the naturally-derived antimicrobial compounds (e.g., hydroxycinnamic acids, terpenes, marine-derived polysaccharides, phenolic compounds) into the naturally derived extracts as a combination therapy to treat the bacterial infection has not been well studied. Objective: The present study was aimed to prepare green algae Ulva lactuca extract and evaluate its antibacterial activity towards Gram-positive and Gram-negative human pathogenic bacteria. Also, revitalize the antibacterial efficiency of the naturally-derived antimicrobial drugs and conventional antibiotics by augmenting their sub-MIC to the U. lactuca extracts. Methods: Extraction was done using a different organic solvent, and its antibacterial activity was tested towards Gram-positive and Gram-negative pathogens. The minimum inhibitory concentration (MIC) of U. lactuca extracts has been determined towards pathogenic bacteria using the micro broth dilution method. The viable cell counting method was used to determine the minimum bactericidal concentration (MBC). The fractional inhibitory concentration (FIC) assay was utilized to examine the combinatorial impact of sub-MIC of two antibacterial drugs using the micro broth dilution method. The chemical components of the extract were analyzed by GC-MS analysis. Results: Among all the extracts, n-hexane extract was found to show effective antibacterial activity towards tested pathogens with the lowest MIC and MBC value. Furthermore, the n-hexane extracts have also been used to enhance the efficacy of the naturally-derived (derived from plants and marine organisms) compounds and conventional antibiotics at their sub-inhibitory concentrations. Most of the tested antibiotics and natural drugs at their sub-MIC were found to exhibit synergistic and additive antibacterial activity towards the tested bacterial pathogens. Conclusions: The augmenting of U. lactuca n-hexane extracts resulted in synergistic and additive bactericidal effects on Gram-positive and Gram-negative human pathogenic bacteria. The present study shows a new alternative strategy to revitalize the antimicrobial activity of naturally derived compounds for treating human bacterial pathogens.

scholarly journals In VitroActivity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Andrew Walkty ◽  
James A. Karlowsky ◽  
Melanie R. Baxter ◽  
Heather J. Adam ◽  
George G. Zhanel
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTThe Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate thein vitroactivities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potentin vitroactivity againstEnterobacteriaceae(MIC90≤ 1 µg/ml for all species tested exceptProteus mirabilisandMorganella morganii), including aminoglycoside-nonsusceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates ofStaphylococcus aureus.

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