New generation of peptide antibiotics.

The increasing antibiotic resistance of pathogenic bacteria calls for the development of alternative antimicrobial strategies. Possible approaches include the development of novel, broad-spectrum antibiotics as well as specific targeting of individual bacterial virulence factors. It is impossible to decide currently which strategy will prove more successful in the future since they both promise different advantages, but also introduce diverse problems. Considering both approaches, our laboratory's research focuses on the evaluation of hemocidins, broad-spectrum antibacterial peptides derived from hemoglobin and myoglobin, and staphostatins, specific inhibitors of staphopains -- Staphylococcus aureus secreted proteases that are virulence factors regarded as possible targets for therapy. The article summarizes recent advances in both fields of study and presents perspectives for further development and possible applications.

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Effect of Thiophenone Compound on Motility and Caseinase Production of Aeromonas hydrophila

Advances in Tropical Biodiversity and Environmental Sciences ◽

10.24843/atbes.2021.v05.i02.p01 ◽

2021 ◽

Vol 5 (2) ◽

pp. 40

Author(s):

Ayu Ashari Margareth Sinaga ◽

Pande Gde Sasmita Julyantotro ◽

Dewa Ayu Angga Pebriani

Keyword(s):

Enzyme Activity ◽

Virulence Factors ◽

Intercellular Communication ◽

Communication System ◽

Aeromonas Hydrophila ◽

Enzyme Production ◽

Pathogenic Bacteria ◽

Average Diameter ◽

Bacterial Virulence ◽

Fisheries Science

Motility and caseinase production are part of bacterial virulence factors which are regulated by a bacterial intercellular communication system, often called quorum sensing (QS). This study aims to determine the effect of the QS inhibitor compound thiophenone in reducing those virulence factors. This research was conducted at the Laboratory of Fisheries Science, Faculty of Marine Science and Fisheries, Udayana University, from December 2019 to March 2020. This study tested 3 different treatments with 3 repetitions for each treatment. Treatment A as control (without the addition of thiophenone), treatment B (addition of 5 ?M thiophenone), and C treatment (addition of 10 ?M thiophenone). The results showed that thiophenone compounds can inhibit the QS system of Aeromonas hydrophila. It can be seen from the significantly reduced (P<0.05) motility and caseinase enzyme activity of A. hydrophila compared to without addition of thiophenone compounds. The average diameter of the caseinase enzyme production produced in treatment A at 22 hours was 21.40±0.36 mm, in treatment B was 19.70±0.2 mm and in treatment, C was 17.87±0.05 mm. Whereas in motility, the resulting average diameter in treatment A at 22 hours was 6.57±0.61 mm, in treatment B was 5.67±0.35 mm and in treatment, C was 5.10±0.6 mm. These results indicate that the QS thiophenone inhibitor compound can reduce virulence factors, namely motility and caseinase production from pathogenic bacteria A. hydrophila. Treatment C can decrease virulence factors compared to treatment A and B.

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A Structural Approach to Anti-Virulence: A Discovery Pipeline

Microorganisms ◽

10.3390/microorganisms9122514 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2514

Author(s):

Michael McCarthy ◽

Monica Goncalves ◽

Hannah Powell ◽

Blake Morey ◽

Madison Turner ◽

...

Keyword(s):

Host Cell ◽

Virulence Factors ◽

Pathogenic Bacteria ◽

Bacterial Virulence ◽

Structural Approach ◽

Multi Drug Resistance ◽

Enzyme Active Site ◽

Catalytic Function ◽

Molecule Inhibitor ◽

High Resolution Structure

The anti-virulence strategy is designed to prevent bacterial virulence factors produced by pathogenic bacteria from initiating and sustaining an infection. One family of bacterial virulence factors is the mono-ADP-ribosyltransferase toxins, which are produced by pathogens as tools to compromise the target host cell. These toxins are bacterial enzymes that exploit host cellular NAD+ as the donor substrate to modify an essential macromolecule acceptor target in the host cell. This biochemical reaction modifies the target macromolecule (often protein or DNA) and functions in a binary fashion to turn the target activity on or off by blocking or impairing a critical process or pathway in the host. A structural biology approach to the anti-virulence method to neutralize the cytotoxic effect of these factors requires the search and design of small molecules that bind tightly to the enzyme active site and prevent catalytic function essentially disarming the pathogen. This method requires a high-resolution structure to serve as the model for small molecule inhibitor development, which illuminates the path to drug development. This alternative strategy to antibiotic therapy represents a paradigm shift that may circumvent multi-drug resistance in the offending microbe through anti-virulence therapy. In this report, the rationale for the anti-virulence structural approach will be discussed along with recent efforts to apply this method to treat honey bee diseases using natural products.

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Prodigiosin inhibits bacterial growth and virulence factors as a potential physiological response to interspecies competition

PLoS ONE ◽

10.1371/journal.pone.0253445 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253445

Author(s):

Chee-Hoo Yip ◽

Sobina Mahalingam ◽

Kiew-Lian Wan ◽

Sheila Nathan

Keyword(s):

Staphylococcus Aureus ◽

Liquid Chromatography ◽

Virulence Factors ◽

Bacterial Growth ◽

Biofilm Formation ◽

Pathogenic Bacteria ◽

Bacterial Virulence ◽

Protease Production ◽

Natural Soil ◽

Microbial Competition

Prodigiosin, a red linear tripyrrole pigment, has long been recognised for its antimicrobial property. However, the physiological contribution of prodigiosin to the survival of its producing hosts still remains undefined. Hence, the aim of this study was to investigate the biological role of prodigiosin from Serratia marcescens, particularly in microbial competition through its antimicrobial activity, towards the growth and secreted virulence factors of four clinical pathogenic bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa) as well as Staphylococcus aureus and Escherichia coli. Prodigiosin was first extracted from S. marcescens and its purity confirmed by absorption spectrum, high performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). The extracted prodigiosin was antagonistic towards all the tested bacteria. A disc-diffusion assay showed that prodigiosin is more selective towards Gram-positive bacteria and inhibited the growth of MRSA, S. aureus and E. faecalis and Gram-negative E. coli. A minimum inhibitory concentration of 10 μg/μL of prodigiosin was required to inhibit the growth of S. aureus, E. coli and E. faecalis whereas > 10 μg/μL was required to inhibit MRSA growth. We further assessed the effect of prodigiosin towards bacterial virulence factors such as haemolysin and production of protease as well as on biofilm formation. Prodigiosin did not inhibit haemolysis activity of clinically associated bacteria but was able to reduce protease activity for MRSA, E. coli and E. faecalis as well as decrease E. faecalis, Salmonella Typhimurium and E. coli biofilm formation. Results of this study show that in addition to its role in inhibiting bacterial growth, prodigiosin also inhibits the bacterial virulence factor protease production and biofilm formation, two strategies employed by bacteria in response to microbial competition. As clinical pathogens were more resistant to prodigiosin, we propose that prodigiosin is physiologically important for S. marcescens to compete against other bacteria in its natural soil and surface water environments.

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mRNA Regulatory elements and bacterial virulence.

Acta Biochimica Polonica ◽

10.18388/abp.2014_1924 ◽

2014 ◽

Vol 61 (1) ◽

Author(s):

Małgorzata Pawlikowska-Warych ◽

Wiesław Deptuła

Keyword(s):

Virulence Factors ◽

Pathogenic Bacteria ◽

Regulatory Elements ◽

Bacterial Virulence ◽

Non Coding Rna

Pathogenic bacteria cause many diseases, some of which are fatal. For researchers, it is a challenge to understand bacterial mechanisms of pathogenicity, including their virulence pathways regulated by RNA. This work presents data on the mechanisms of regulation and expression of several virulence factors coded by RNA, namely 5' UTR fragments, riboswitches and small non-coding RNA (sRNA).

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Preliminary in Vitro Investigations on The Inhibitory Activity of The Original Dietary Supplement Oxidal® on Pathogenic Bacterial Strains

JOURNAL OF ADVANCES IN AGRICULTURE ◽

10.24297/jaa.v11i.8693 ◽

2020 ◽

Vol 11 ◽

pp. 37-43

Author(s):

Prof. Teodora P. Popova ◽

Toshka Petrova ◽

Ignat Ignatov ◽

Stoil Karadzhov

Keyword(s):

Dietary Supplement ◽

Broad Spectrum ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Clinical Effectiveness ◽

Inhibitory Effect ◽

Diffusion Method ◽

Bacterial Strains ◽

Microbial Strains

The antimicrobial action of the dietary supplement Oxidal® was tested using the classic Bauer and Kirby agar-gel diffusion method. Clinical and reference strains of Staphylococcus aureus and Escherichia coli were used in the studies. The tested dietary supplement showed a well-pronounced inhibitory effect against the microbial strains commensurable with that of the broad-spectrum chemotherapeutic agent Enrofloxacin and showed even higher activity than the broad spectrum antibiotic Thiamphenicol. The proven inhibitory effect of the tested dietary supplement against the examined pathogenic bacteria is in accordance with the established clinical effectiveness standards for antimicrobial agents.

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Faculty Opinions recommendation of Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160071.623233 ◽

2009 ◽

Author(s):

Fergal O'Gara

Keyword(s):

Pseudomonas Aeruginosa ◽

Outer Membrane ◽

Virulence Factors ◽

Membrane Vesicles ◽

Outer Membrane Vesicles ◽

Bacterial Virulence ◽

Long Distance ◽

Distance Delivery

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Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190121105851 ◽

2019 ◽

Vol 18 (31) ◽

pp. 2731-2740 ◽

Cited By ~ 3

Author(s):

Sandeep Tiwari ◽

Debmalya Barh ◽

M. Imchen ◽

Eswar Rao ◽

Ranjith K. Kumavath ◽

...

Keyword(s):

Broad Spectrum ◽

In Silico ◽

Pathogenic Bacteria ◽

In Vitro Study ◽

Docking Studies ◽

Acetate Kinase ◽

E Coli ◽

Pathogenic Escherichia Coli ◽

Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

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