Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria

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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Probiotic mechanisms of action

Early Human Development ◽

10.1016/j.earlhumdev.2019.05.010 ◽

2019 ◽

Vol 135 ◽

pp. 58-65 ◽

Cited By ~ 12

Author(s):

Katrina Halloran ◽

Mark A. Underwood

Keyword(s):

Mechanisms Of Action ◽

Probiotic Mechanisms

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Probiotic Mechanisms of Action

Annals of Nutrition and Metabolism ◽

10.1159/000342079 ◽

2012 ◽

Vol 61 (2) ◽

pp. 160-174 ◽

Cited By ~ 357

Author(s):

Miriam Bermudez-Brito ◽

Julio Plaza-Díaz ◽

Sergio Muñoz-Quezada ◽

Carolina Gómez-Llorente ◽

Angel Gil

Keyword(s):

Mechanisms Of Action ◽

Probiotic Mechanisms

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Antibiotics are Passe: Take a Look at Probiotics

World Journal of Dentistry ◽

10.5005/jp-journals-10015-1022 ◽

2010 ◽

Vol 1 (2) ◽

pp. 109-111

Author(s):

M Manjunath ◽

TA Deepak ◽

Shubha Pewa

Keyword(s):

Immune System ◽

Pathogenic Bacteria ◽

Mark Twain ◽

Mechanisms Of Action ◽

Attachment Sites ◽

Good For ◽

Metabolic Activities ◽

Digestive Health

ABSTRACT “Part of the secret of success in life is to eat, what you like and let the food fight it out inside.” —Mark Twain This age—old quote was probably the first reference to a relatively novel group of organisms fondly known as ‘probiotics’. Probiotics are live organisms that alter the composition or metabolic activities of the microbiota, or to modulate immune system reactivity in a way that benefits our health. In other words, they are microorganisms good for our health. To achieve this, probiotics actively ‘compete’ with pathogenic bacteria for attachment sites, nutrition, etc. Probiotics are also beneficial by eliminating the toxins produced by pathogens, hereby rendering them invalid. Research surrounding probiotics has historically focused on digestive health. Over recent years, scientists have been investigating the potential immune benefits of probiotics, as well as other benefits beyond the recognized area of gut. This article attempts to summarize the mechanisms of action of probiotics with a brief overview of some of the oral benefits of certain probiotics organisms.

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Targeted Therapeutic Strategies in the Battle Against Pathogenic Bacteria

Frontiers in Pharmacology ◽

10.3389/fphar.2021.673239 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bingqing Yang ◽

Dan Fang ◽

Qingyan Lv ◽

Zhiqiang Wang ◽

Yuan Liu

Keyword(s):

Public Health ◽

Pathogenic Bacteria ◽

Phage Therapy ◽

Critical Role ◽

Therapeutic Strategies ◽

Mechanisms Of Action ◽

Modern Technology ◽

Rapid Spread ◽

Target Therapies ◽

Global Threat

The emergence and rapid spread of antibiotic resistance in pathogenic bacteria constitute a global threat for public health. Despite ongoing efforts to confront this crisis, the pace of finding new potent antimicrobials is far slower than the evolution of drug resistance. The abuse of broad-spectrum antibiotics not only accelerates the formation of resistance but also imposes a burden on the intestinal microbiota, which acts a critical role in human homeostasis. As such, innovative therapeutic strategies with precision are pressingly warranted and highly anticipated. Recently, target therapies have achieved some breakthroughs by the aid of modern technology. In this review, we provide an insightful illustration of current and future medical targeted strategies, including narrow-spectrum agents, engineered probiotics, nanotechnology, phage therapy, and CRISPR-Cas9 technology. We discuss the recent advances and potential hurdles of these strategies. Meanwhile, the possibilities to mitigate the spread of resistance in these approaches are also mentioned. Altogether, a better understanding of the advantages, disadvantages, and mechanisms of action of these targeted therapies will be conducive to broadening our horizons and optimizing the existing antibacterial approaches.

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Multi-omic characterisation of Streptomyces hygroscopicus NRRL 30439: detailed assessment of its secondary metabolic potential

Molecular Omics ◽

10.1039/d1mo00150g ◽

2022 ◽

Author(s):

Craig Patrick Barry ◽

Rosemary Gillane ◽

Gert Hoy Talbo ◽

Manuel Plan ◽

Robin Palfreyman ◽

...

Keyword(s):

Genome Sequencing ◽

Paradigm Shift ◽

Pathogenic Bacteria ◽

Multidrug Resistant ◽

Mechanisms Of Action ◽

Streptomyces Hygroscopicus ◽

Next Generation ◽

Metabolic Potential ◽

Detailed Assessment ◽

Novel Antibiotics

The emergence of multidrug-resistant pathogenic bacteria creates a demand for novel antibiotics with distinct mechanisms of action. Advances in next-generation genome sequencing promised a paradigm shift in the quest to...

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Potential use of silver nanoparticles on pathogenic bacteria, their toxicity and possible mechanisms of action

Journal of the Brazilian Chemical Society ◽

10.1590/s0103-50532010000600002 ◽

2010 ◽

Vol 21 (6) ◽

pp. 949-959 ◽

Cited By ~ 244

Author(s):

Nelson Durán ◽

Priscyla D. Marcato ◽

Roseli De Conti ◽

Oswaldo L. Alves ◽

Fabio T. M. Costa ◽

...

Keyword(s):

Silver Nanoparticles ◽

Pathogenic Bacteria ◽

Mechanisms Of Action ◽

Potential Use

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Amplified Detection of Transcriptional and Translational Inhibitors in Bioluminescent Escherichia Coli K-12

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057103008003012 ◽

2003 ◽

Vol 8 (3) ◽

pp. 340-346 ◽

Cited By ~ 7

Author(s):

Lorenzo Galluzzi ◽

Matti Karp

Keyword(s):

Escherichia Coli ◽

High Throughput Screening ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Mechanisms Of Action ◽

Genetically Engineered ◽

Molecular Structures ◽

Fast Method ◽

Freeze Dried ◽

K 12

The excessive prescription of antimicrobial agents and their use as animal growth promoters lead to the spread of resistance among pathogenic bacteria. Consequently, unnecessary use should be minimized, and new chemicals with novel mechanisms of action are needed. The authors have developed a fast method to measure the activity of antibiotics by means of a genetically engineered strain of Escherichia coli K-12. The system is based on the full-length bacterial luciferase operon coupled to the tetracycline-inducible tetA promoter in the reporter plasmid pTetLux1. Sublethal doses of tetracycline are used to start the luciferase synthesis in cultures that were previously incubated with the antibiotic under investigation. After a variable time frame—from 1 to 4 h, depending on the antimicrobial mode of action—the level of light emission from treated cultures is compared to the level obtained in control cultures. The gap in bioluminescence outlines the antibiotic interference in bacterial metabolism. Throughout this study, freeze-dried sensor cells were used to avoid repeated cultures from day to day. The authors show the results of 10 model antibiotics, representing different molecular structures and mechanisms of action. The results show that no actively dividing cells are needed for sensitive responses, especially when transcriptional and translational inhibitors, directly interfering with the luciferase production, are tested. The assay can be easily automated for high-throughput screening purposes of pharmaceutical industry. ( Journal of Biomolecular Screening 2003:340-346)

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Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS)

Molecules ◽

10.3390/molecules24081638 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1638 ◽

Cited By ~ 1

Author(s):

Cecilia Pozzi ◽

Ludovica Lopresti ◽

Giusy Tassone ◽

Stefano Mangani

Keyword(s):

Thymidylate Synthase ◽

Pathogenic Bacteria ◽

De Novo ◽

Functional Characterization ◽

Mechanisms Of Action ◽

Human Pathogenic Bacteria ◽

Thymidylate Synthases ◽

Open Debate ◽

Definition Of

In cells, thymidylate synthases provide the only de novo source of 2′-deoxythymidine-5′-monophosphate (dTMP), required for DNA synthesis. The activity of these enzymes is pivotal for cell survival and proliferation. Two main families of thymidylate synthases have been identified in bacteria, folate-dependent thymidylate synthase (TS) and flavin-dependent TS (FDTS). TS and FDTS are highly divergent enzymes, characterized by exclusive catalytic mechanisms, involving different sets of cofactors. TS and FDTS mechanisms of action have been recently revised, providing new perspectives for the development of antibacterial drugs targeting these enzymes. Nonetheless, some catalytic details still remain elusive. For bacterial TSs, half-site reactivity is still an open debate and the recent evidences are somehow controversial. Furthermore, different behaviors have been identified among bacterial TSs, compromising the definition of common mechanisms. Moreover, the redox reaction responsible for the regeneration of reduced flavin in FDTSs is not completely clarified. This review describes the recent advances in the structural and functional characterization of bacterial TSs and FDTSs and the current understanding of their mechanisms of action. Furthermore, the recent progresses in the development of inhibitors targeting TS and FDTS in human pathogenic bacteria are summarized.

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Antibacterial Peptides from Plants: What They Are and How They Probably Work

Biochemistry Research International ◽

10.1155/2011/250349 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 62

Author(s):

Patrícia Barbosa Pelegrini ◽

Rafael Perseghini del Sarto ◽

Osmar Nascimento Silva ◽

Octávio Luiz Franco ◽

Maria Fátima Grossi-de-Sa

Keyword(s):

Cell Wall ◽

Mechanism Of Action ◽

Pathogenic Bacteria ◽

Membrane Surface ◽

Three Dimensional ◽

Mechanisms Of Action ◽

Bacterial Membrane ◽

Antibacterial Peptides ◽

Disulphide Bonds ◽

Plant Peptides

Plant antibacterial peptides have been isolated from a wide variety of species. They consist of several protein groups with different features, such as the overall charge of the molecule, the content of disulphide bonds, and structural stability under environmental stress. Although the three-dimensional structures of several classes of plant peptides are well determined, the mechanism of action of some of these molecules is still not well defined. However, further studies may provide new evidences for their function on bacterial cell wall. Therefore, this paper focuses on plant peptides that show activity against plant-pathogenic and human-pathogenic bacteria. Furthermore, we describe the folding of several peptides and similarities among their three-dimensional structures. Some hypotheses for their mechanisms of action and attack on the bacterial membrane surface are also proposed.

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