scholarly journals Gene expression in Lucilia sericata (Diptera: Calliphoridae) larvae exposed to Pseudomonas aeruginosa and Acinetobacter baumanii identifies shared and microbe-specific induction of immune genes

2021 ◽  
Author(s):  
Claire H McKenna ◽  
Danial Asgari ◽  
Tawni C Crippen ◽  
Le Zheng ◽  
Ronald A Sherman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Molecular Level ◽  
Lucilia Sericata ◽  
Acinetobacter Baumanii ◽  
Wound Debridement ◽  
Immune Genes ◽  
Specific Induction ◽  
Deficiency Gene

Antibiotic resistance is a continuing challenge in medicine. There are various strategies for expanding antibiotic therapeutic repertoires, including the use of blow flies. Their larvae exhibit strong antibiotic and antibiofilm properties that alter microbiome communities. One species, Lucilia sericata, is used to treat problematic wounds due to its debridement capabilities and its excretions and secretions that kill some pathogenic bacteria. There is much to be learned about how L. sericata interacts with microbiomes at the molecular level. To address this deficiency, gene expression was assessed after feeding exposure (1 hour or 4 hours) to two clinically problematic pathogens: Pseudomonas aeruginosa and Acinetobacter baumanii. The results identified immunity related genes that were differentially expressed when exposed to these pathogens, as well as non-immune genes possibly involved in gut responses to bacterial infection. There was a greater response to P. aeruginosa that increased over time, while few genes responded to A. baumanii exposure and expression was not time-dependent. The response to feeding on pathogens indicates a few common responses and features distinct to each pathogen, which is useful in improving wound debridement therapy and helps develop biomimetic alternatives.

Immunomodulatory Effect of “Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy” to Cure or Prevent Hospital Acquired (Nosocomial) Infections due to Clostridium difficile (C. diff), other Pathogenic Bacteria, and Autoimmune Diseases

2018 ◽  
Vol 11 (1) ◽  
pp. 3937-3949
Author(s):  
Malireddy S Reddy
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Pathogenic Bacteria ◽  
Molecular Level ◽  
Host Immune System ◽  
Hospital Acquired Infections ◽  
The World ◽  
Probiotic Strains ◽  
The Individual ◽  
Hospital Acquired

The worldwide popularity of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to treat or prevent the hospital acquired infections (nosocomial infections) arose a great interest in the medical community around the world (Reddy and Reddy, 2016; 2017). The following questions were raised on this subject: Does Multiple Mixed Strain Probiotics directly inhibit the pathogenic bacteria (C. diff) in the gastrointestinal tract or indirectly through modulation of the host immune system or both? To be more specific, what is the exact and/or hypothetical mechanism at molecular level behind the breakthrough discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy?  To answer these questions, the specific immunomodulation regulatory functions of the individual Probiotic strains (on host) have beenresearched, investigated andoutlined in this article.  A detailed explanation(s) and hypotheses have been proposed outlining the possible cumulativedirect bacteriological and indirect immunomodulatory effects (at the molecular level) of the Multiple Mixed Strain Probiotics used in Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to successfully treat C. diff infection.  A detailed scientific and research attempts were made to correlate the Probiotic induced immune activities in relation to the reduction of the symptoms associated with the hospital acquired Clostridium difficile infection during and after the Multiple Mixed Strain Probioitc Therapy.  Results of the clinical trials, microbiological tests on feces, and the clinical blood tests significantly revealed that the reasons for the success of Dr. Reddy’s Multiple Mixed Strain Probiotic Therapy are multifold. Presumably, it is predominantly due to the immunomodulatory effect they have exerted on the host immune system along with the direct inhibition of C. diff bacteria by multiple Probiotics, due to the production of bacteriocins, lactic acid and nutritional competency.In addition, the size of the individual cells of the Probiotic strains in the Multiple Mixed Strain Probiotics and their significant effect on immunomodulation has been thoroughly discussed. Results clearly proved that if Probiotics are absent in the GI tract during C. diff infection, the chances of patient survival is zero.  This is because of the excess immune stimulation and incurable damage to the epithelial cell barrier of the gastrointestinal tract caused by C. diff bacteria.  The results also revealed, without any doubt, as of to-datethe latest discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy is the best way to cure the deadly hospital acquired infections affecting millions of people around the world, with high degree of mortality.  This has been attested by several practicng medical professionals and scientists around the world (Reddy and Reddy, 2017).

Microbiological quality of residues from drinking water preparation

1995 ◽  
Vol 31 (5-6) ◽  
pp. 75-79 ◽  
Author(s):  
M. Würzer ◽  
A. Wiedenmann ◽  
K. Botzenhart
Keyword(s):  
Waste Water ◽  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Drinking Water ◽  
Water Treatment ◽  
Pathogenic Bacteria ◽  
Waste Water Treatment ◽  
Microbiological Quality ◽  
Detection Limits

In Germany the application of procedures such as flocculation and filtration in the preparation of drinking water results in the annual production of an estimated 500,000 t of sediments and sludges. Some of these residues have a potential for being reused, for example in agriculture, forestry, brickworks or waste water treatment. To assess the microbiological quality of residues from waterworks methods for the detection of enterobacteria, Escherichia coli, Salmonella, Pseudomonas aeruginosa, Legionella, poliovirus, Ascaris suis eggs and Cryptosporidium have been evaluated regarding their detection limits and were applied to various residues from German waterworks. Results show that sediments and sludges may contain pathogenic bacteria, viruses and protista. When residues from waterworks are intended to be reused in agriculture or forestry the microbiological quality should therefore be considered.

scholarly journals Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 414
Author(s):  
Didem Kart ◽  
Tuba Reçber ◽  
Emirhan Nemutlu ◽  
Meral Sagiroglu
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Inhibitory Concentration ◽  
Molecular Level ◽  
Metabolomic Profile ◽  
Gene Expressions ◽  
New Agents ◽  
Qrt Pcr ◽  
Metabolomic Approach

Introduction: Alternative anti-biofilm agents are needed to combat Pseudomonas aeruginosa infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on P. aeruginosa biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on P. aeruginosa in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively. Results: The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on P. aeruginosa in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and lasI expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated P. aeruginosa growth inhibition. Conclusions: The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against P. aeruginosa biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of P. aeruginosa biofilms through metabolomic pathways.

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

scholarly journals Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 745
Author(s):  
Melaine González-García ◽  
Fidel Morales-Vicente ◽  
Erbio Díaz Pico ◽  
Hilda Garay ◽  
Daniel G. Rivera ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Multidrug Resistant ◽  
Moderate Activity ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Acinetobacter Baumanii ◽  
Concentration Dependent Manner ◽  
Conventional Antibiotics

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.

scholarly journals Strain-Dependent Adsorption of Pseudomonas aeruginosa-Derived Adhesin-like Peptides at Abiotic Surfaces

Micro ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 129-139
Author(s):  
Yu Yang ◽  
Sabrina Schwiderek ◽  
Guido Grundmeier ◽  
Adrian Keller
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Level ◽  
Microbial Colonization ◽  
Peptide Sequence ◽  
Type Iv ◽  
Research Activities ◽  
Abiotic Surfaces ◽  
Peptide Adsorption ◽  
Pilin Protein ◽  
Strain Dependent

Implant-associated infections are an increasingly severe burden on healthcare systems worldwide and many research activities currently focus on inhibiting microbial colonization of biomedically relevant surfaces. To obtain molecular-level understanding of the involved processes and interactions, we investigate the adsorption of synthetic adhesin-like peptide sequences derived from the type IV pili of the Pseudomonas aeruginosa strains PAK and PAO at abiotic model surfaces, i.e., Au, SiO2, and oxidized Ti. These peptides correspond to the sequences of the receptor-binding domain 128–144 of the major pilin protein, which is known to facilitate P. aeruginosa adhesion at biotic and abiotic surfaces. Using quartz crystal microbalance with dissipation monitoring (QCM-D), we find that peptide adsorption is material- as well as strain-dependent. At the Au surface, PAO(128–144) shows drastically stronger adsorption than PAK(128–144), whereas adsorption of both peptides is markedly reduced at the oxide surfaces with less drastic differences between the two sequences. These observations suggest that peptide adsorption is influenced by not only the peptide sequence, but also peptide conformation. Our results furthermore highlight the importance of molecular-level investigations to understand and ultimately control microbial colonization of surfaces.

scholarly journals High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials

2020 ◽  
Vol 367 (22) ◽  
Author(s):  
Chris Coward ◽  
Gopujara Dharmalingham ◽  
Omar Abdulle ◽  
Tim Avis ◽  
Stephan Beisken ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Selective Advantage ◽  
Mechanisms Of Action ◽  
Over Expression ◽  
E Coli ◽  
Synthase Inhibitor ◽  
Established Technique ◽  
Bacterial Transposon

ABSTRACT The use of bacterial transposon mutant libraries in phenotypic screens is a well-established technique for determining which genes are essential or advantageous for growth in conditions of interest. Standard, inactivating, transposon libraries cannot give direct information about genes whose over-expression gives a selective advantage. We report the development of a system wherein outward-oriented promoters are included in mini-transposons, generation of transposon mutant libraries in Escherichia coli and Pseudomonas aeruginosa and their use to probe genes important for growth under selection with the antimicrobial fosfomycin, and a recently-developed leucyl-tRNA synthase inhibitor. In addition to the identification of known mechanisms of action and resistance, we identify the carbon–phosphorous lyase complex as a potential resistance liability for fosfomycin in E. coli and P. aeruginosa. The use of this technology can facilitate the development of novel mechanism-of-action antimicrobials that are urgently required to combat the increasing threat worldwide from antimicrobial-resistant pathogenic bacteria.

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