Antibiotic Alternatives: Virulence Factors Produced by Pathogenic Bacteria

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 21390

Special Issue Editor


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Guest Editor
Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015, USA
Interests: anti-virulence strategies; bacterial toxins; aggregatibacter actinomycetemcomitans; repeats-in-toxin

Special Issue Information

Dear Colleagues,

The World Health Organization recently named antimicrobial resistance to be one of the ten largest global health issues. In the United States alone, more than 35,000 people die each year because of antibiotic resistant infections. As the number of antibiotic infections continues to increase, once easily treated infections have become medical emergencies. A promising alternative approach is to focus on mitigating the effect of bacterial virulence factors. A number of studies exist demonstrating the effectiveness of these anti-virulence approaches in vitro, but in vivo translation has been difficult for a number of reasons. This Special Issue seeks manuscript submissions that advance our understanding of the potential and limitations of antivirulence strategies in infectious disease. Submissions dealing with any aspect of antivirulence are welcome.

Prof. Angela Brown
Guest Editor

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Keywords

  • antibiotic resistance
  • antivirulence
  • virulence factor
  • pathogenic bacteria

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Published Papers (4 papers)

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Research

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14 pages, 1792 KiB  
Article
β-Lytic Protease of Lysobacter capsici VKM B-2533T
by Alexey S. Afoshin, Mihail A. Konstantinov, Ilya Yu. Toropygin, Irina V. Kudryakova and Natalia V. Vasilyeva
Antibiotics 2020, 9(11), 744; https://doi.org/10.3390/antibiotics9110744 - 28 Oct 2020
Cited by 6 | Viewed by 2603
Abstract
Bacteriolytic enzymes are promising antimicrobial agents for developing new-generation drugs. Recently, we have isolated a β-lytic protease (BlpLc) from the culture liquid of Lysobacter capsici VKM B-2533T. This BlpLc possesses a valuable property, not described for β-lytic proteases (Blps) earlier, of [...] Read more.
Bacteriolytic enzymes are promising antimicrobial agents for developing new-generation drugs. Recently, we have isolated a β-lytic protease (BlpLc) from the culture liquid of Lysobacter capsici VKM B-2533T. This BlpLc possesses a valuable property, not described for β-lytic proteases (Blps) earlier, of hydrolyzing living cells of Staphylococcus aureus 55 MRSA clinical isolate. This work phylogenetically characterized the BlpLc and investigated its properties. Analysis revealed a variability of pre-/pro-parts of Blp precursors. The mature BlpLc is the closest to the earlier annotated but not isolated Blp from Lysobacter sp. Root690. The biochemical characterization found conditions for the BlpLc general bacteriolytic activity relative to autoclaved S. aureus 209P cells to differ from that of earlier isolated Blp. Unexpected was the effect of serine (phenylmethylsulfonyl fluoride (PMSF)) and cysteine (p-chloromercuribenzoate (p-CMB)) protease inhibitors on BlpLc bacteriolytic and proteolytic activities. The specificity of BlpLc proteolytic action relative to hemoglobin, elastin, gelatin, collagen, azofibrin, myoglobin, ovalbumin, and ovamucoid was found. New types of peptide bonds—Gly-X, Ser-X, Lys-X, Ala-X, Val-X, Glu-X, and Phe-X—hydrolyzed by the enzyme in protein substrates were first revealed using MALDI-TOF. Turbidimetrically, the BlpLc was found to lyze living cells of S. aureus 209P, Micrococcus luteus B1819, and M. roseus B1236, which is important for expanding the enzyme’s applied properties. Full article
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Review

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30 pages, 2562 KiB  
Review
Anti-Virulence Therapeutic Approaches for Neisseria gonorrhoeae
by Katherine Y. L. Lim, Christopher A. Mullally, Ethan C. Haese, Emily A. Kibble, Nicolie R. McCluskey, Edward C. Mikucki, Van C. Thai, Keith A. Stubbs, Mitali Sarkar-Tyson and Charlene M. Kahler
Antibiotics 2021, 10(2), 103; https://doi.org/10.3390/antibiotics10020103 - 21 Jan 2021
Cited by 14 | Viewed by 7327
Abstract
While antimicrobial resistance (AMR) is seen in both Neisseria gonorrhoeae and Neisseria meningitidis, the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways [...] Read more.
While antimicrobial resistance (AMR) is seen in both Neisseria gonorrhoeae and Neisseria meningitidis, the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways leading to the development of AMR. This review highlights the growing research interest in developing anti-virulence therapies (AVTs) which are directed towards inhibiting virulence factors to prevent infection. By targeting virulence factors that are not essential for gonococcal survival, it is hypothesized that this will impart a smaller selective pressure for the emergence of resistance in the pathogen and in the microbiome, thus avoiding AMR development to the anti-infective. This review summates the current basis of numerous anti-virulence strategies being explored for N. gonorrhoeae. Full article
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11 pages, 253 KiB  
Review
Relationship between Virulence and Resistance among Gram-Negative Bacteria
by Virginio Cepas and Sara M. Soto
Antibiotics 2020, 9(10), 719; https://doi.org/10.3390/antibiotics9100719 - 20 Oct 2020
Cited by 63 | Viewed by 6099
Abstract
Bacteria present in the human body are innocuous, providing beneficial functions, some of which are necessary for correct body function. However, other bacteria are able to colonize, invade, and cause damage to different tissues, and these are categorised as pathogens. These pathogenic bacteria [...] Read more.
Bacteria present in the human body are innocuous, providing beneficial functions, some of which are necessary for correct body function. However, other bacteria are able to colonize, invade, and cause damage to different tissues, and these are categorised as pathogens. These pathogenic bacteria possess several factors that enable them to be more virulent and cause infection. Bacteria have a great capacity to adapt to different niches and environmental conditions (presence of antibiotics, iron depletion, etc.). Antibiotic pressure has favoured the emergence and spread of antibiotic-resistant bacteria worldwide. Several studies have reported the presence of a relationship (both positive and negative, and both direct and indirect) between antimicrobial resistance and virulence among bacterial pathogens. This review studies the relationship among the most important Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) taking into account two points of view: (i) the effect the acquisition of resistance has on virulence, and (ii) co-selection of resistance and virulence. The relationship between resistance and virulence among bacteria depends on the bacterial species, the specific mechanisms of resistance and virulence, the ecological niche, and the host. Full article

Other

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11 pages, 250 KiB  
Perspective
The Not-So-Strange Case of Dr. Jekyll and Mr. Hyde in Antibiotic Research: An Interdisciplinary Opportunity
by Lorenzo Servitje
Antibiotics 2021, 10(1), 19; https://doi.org/10.3390/antibiotics10010019 - 28 Dec 2020
Viewed by 4670
Abstract
Literary-rhetorical devices like figurative language and analogy can help explain concepts that exceed our capacity to grasp intuitively. It is not surprising these devices are used to discuss virulence, pathogenesis, and antibiotics. Allusions to Robert Louis Stevenson’s Strange Case of Dr. Jekyll and [...] Read more.
Literary-rhetorical devices like figurative language and analogy can help explain concepts that exceed our capacity to grasp intuitively. It is not surprising these devices are used to discuss virulence, pathogenesis, and antibiotics. Allusions to Robert Louis Stevenson’s Strange Case of Dr. Jekyll and Mr. Hyde seem to be used with particular frequency in research pertaining to pathogens, especially in studies contemporary with our evolving understanding of antibiotic resistance. More recent references to the text have appeared in research parsing definitions of virulence and acknowledging the role of anti-virulence in future therapeutics. While it is obvious that scientists invoke Stevenson’s story for stylistic purposes, its use could go beyond the stylistic—and might even generate rhetorical and imaginative possibilities for framing research. This perspective discusses the first published allusion to Jekyll and Hyde in reference to virulence and pathogenesis; comments on a select number of specific instances of Jekyll and Hyde in contemporary scientific literature; briefly contextualizes the novel; and concludes with the implications of a more productive engagement with humanistic disciplines in the face of antibiotic resistance. Full article
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