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Microbial Resistance Mechanisms
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Microbial Resistance Mechanisms

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 10753

Special Issue Editor

Dr. Michał Arabski

E-Mail Website
Guest Editor
Division of Medical Biology, Jan Kochanowski University, 25-406 Kielce, Poland
Interests: clinical biochemistry; anticancer drugs; cytotoxicity; gene expression; drugs diffusion; new antibacterial agents; host–pathogen interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the dramatic increase in antibiotic resistance in microbes, new knowledge regarding the mechanisms of this drug resistance is important for the development of novel therapies. These microbial resistance mechanisms focus on the modification of a drug target, its uptake limiting, and active efflux from microbial cells. Moreover, in many clinical settings, a biofilm represents a hazardous problem concerning many chronic infections involving these consortia of microbial cells enclosed by a polysaccharide matrix. A biofilm structure protects against antimicrobial agents and can stimulate their resistance mechanisms. The need for new knowledge regarding microbial resistance mechanisms seems crucial and is required for novel antibacterial agent design and applications. In an attempt to gather recent advances in this field, I aim to edit a Special Issue in the International Journal of Molecular Sciences (IF: 5.924) concerning “Microbial Resistance Mechanisms”. This Special Issue focuses on the molecular studies of microbial resistance mechanisms of planktonic or biofilm-forming cells, which might be considered as targets for new drugs action. These two topics of study are welcomed.

Dr. Michał Arabski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic resistance
  • virulence factors
  • biofilm
  • antimicrobial agents
  • peptides
  • bacteriophages
  • lytic proteins
  • metal complexes

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Published Papers (4 papers)

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Research

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16 pages, 3561 KiB  
Article
Heterologous Expression Reveals Ancient Properties of Tei3—A VanS Ortholog from the Teicoplanin Producer Actinoplanes teichomyceticus
by Oleksandr Yushchuk, Kseniia Zhukrovska, Bohdan Ostash, Victor Fedorenko and Flavia Marinelli
Int. J. Mol. Sci. 2022, 23(24), 15713; https://doi.org/10.3390/ijms232415713 - 11 Dec 2022
Cited by 1 | Viewed by 2130
Abstract
Glycopeptide antibiotics (GPAs) are among the most clinically successful antimicrobials. GPAs inhibit cell-wall biosynthesis in Gram-positive bacteria via binding to lipid II. Natural GPAs are produced by various actinobacteria. Being themselves Gram-positives, the GPA producers evolved sophisticated mechanisms of self-resistance to avoid suicide [...] Read more.
Glycopeptide antibiotics (GPAs) are among the most clinically successful antimicrobials. GPAs inhibit cell-wall biosynthesis in Gram-positive bacteria via binding to lipid II. Natural GPAs are produced by various actinobacteria. Being themselves Gram-positives, the GPA producers evolved sophisticated mechanisms of self-resistance to avoid suicide during antibiotic production. These self-resistance genes are considered the primary source of GPA resistance genes actually spreading among pathogenic enterococci and staphylococci. The GPA-resistance mechanism in Actinoplanes teichomyceticus—the producer of the last-resort-drug teicoplanin—has been intensively studied in recent years, posing relevant questions about the role of Tei3 sensor histidine kinase. In the current work, the molecular properties of Tei3 were investigated. The setup of a GPA-responsive assay system in the model Streptomyces coelicolor allowed us to demonstrate that Tei3 functions as a non-inducible kinase, conferring high levels of GPA resistance in A. teichomyceticus. The expression of different truncated versions of tei3 in S. coelicolor indicated that both the transmembrane helices of Tei3 are crucial for proper functioning. Finally, a hybrid gene was constructed, coding for a chimera protein combining the Tei3 sensor domain with the kinase domain of VanS, with the latter being the inducible Tei3 ortholog from S. coelicolor. Surprisingly, such a chimera did not respond to teicoplanin, but indeed to the related GPA A40926. Coupling these experimental results with a further in silico analysis, a novel scenario on GPA-resistance and biosynthetic genes co-evolution in A. teichomyceticus was hereby proposed. Full article
(This article belongs to the Special Issue Microbial Resistance Mechanisms)
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12 pages, 1516 KiB  
Article
Expression and Characterization of Monomeric Recombinant Isocitrate Dehydrogenases from Corynebacterium glutamicum and Azotobacter vinelandii for NADPH Regeneration
by Hun-Dong Lee, Su-Kyoung Yoo, Ho-Seok Yoo, Chul-Ho Yun and Geun-Joong Kim
Int. J. Mol. Sci. 2022, 23(23), 15318; https://doi.org/10.3390/ijms232315318 - 5 Dec 2022
Cited by 3 | Viewed by 2423
Abstract
The enzymatic transformation of various chemicals, especially using NADPH-dependent hydroxylase, into more soluble and/or high value-added products has steadily garnered increasing attention. However, the industrial application of these NADPH-dependent hydroxylases has been limited due to the high cost of the cofactor NADPH. As [...] Read more.
The enzymatic transformation of various chemicals, especially using NADPH-dependent hydroxylase, into more soluble and/or high value-added products has steadily garnered increasing attention. However, the industrial application of these NADPH-dependent hydroxylases has been limited due to the high cost of the cofactor NADPH. As an alternative, enzymatic NADPH-regeneration systems have been developed and are frequently used in various fields. Here, we expressed and compared two recombinant isocitrate dehydrogenases (IDHs) from Corynebacterium glutamicum and Azotobacter vinelandii in Escherichia coli. Both enzymes were hyper-expressed in the soluble fraction of E. coli and were single-step purified to apparent homogeneity with yields of more than 850 mg/L. These enzymes also functioned well when paired with NADPH consumption systems. Specifically, NADPH was regenerated from NADP+ when an NADPH-consuming cytochrome P450 BM3 from Bacillus megaterium was incorporated. Therefore, both enzymes could be used as alternatives to the commonly used regeneration system for NADPH. These enzymes also have promising potential as genetic fusion partners with NADPH-dependent enzymes due to the monomeric nature of their quaternary structure, thereby resulting in self-sufficient biocatalysts via NADPH regeneration in a single polypeptide with NADPH-dependent activity. Full article
(This article belongs to the Special Issue Microbial Resistance Mechanisms)
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Review

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12 pages, 645 KiB  
Review
Gated Calcium Ion Channel and Mutation Mechanisms in Multidrug-Resistant Tuberculosis
by John A. D’Elia and Larry A. Weinrauch
Int. J. Mol. Sci. 2023, 24(11), 9670; https://doi.org/10.3390/ijms24119670 - 2 Jun 2023
Cited by 1 | Viewed by 2050
Abstract
A wide spectrum of Gram-positive/Gram-negative bacteria has been found resistant to a wide spectrum of antibiotics in the United States of America during the past decade. Drug-resistant tuberculosis is not yet a major threat in North/South America, Europe, and the Middle East. However, [...] Read more.
A wide spectrum of Gram-positive/Gram-negative bacteria has been found resistant to a wide spectrum of antibiotics in the United States of America during the past decade. Drug-resistant tuberculosis is not yet a major threat in North/South America, Europe, and the Middle East. However, the migration of populations in times of drought, famine, and hostilities may increase the global reach of this ancient pathogen. Given an increased spread from China and India to African countries, drug-resistant Mycobacterium tuberculosis has become an emerging topic of concern for Europe and North America. Due to the dangers associated with the spread of pathogens among different populations, the World Health Organization continues to expand healthcare advisories for therapeutic approaches for both stationary and migrating populations. As much of the literature focuses on endemic to pandemic viruses, we remain concerned that other treatable communicable diseases may be ignored. One such disease is multidrug-resistant tuberculosis. We focus on molecular mechanisms that this pathogen relies upon for the development of multidrug resistance via gene mutation and the evolutionary development of new enzyme and calcium channels. Full article
(This article belongs to the Special Issue Microbial Resistance Mechanisms)
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19 pages, 2001 KiB  
Review
Peptide Designs for Use in Caries Management: A Systematic Review
by Olivia Lili Zhang, John Yun Niu, Ollie Yiru Yu, May Lei Mei, Nicholas Stephen Jakubovics and Chun Hung Chu
Int. J. Mol. Sci. 2023, 24(4), 4247; https://doi.org/10.3390/ijms24044247 - 20 Feb 2023
Cited by 8 | Viewed by 3055
Abstract
The objective of this study was to review the design methods that have been used to create peptides for use in caries management. Two independent researchers systematically reviewed many in vitro studies in which peptides were designed for use in caries management. They [...] Read more.
The objective of this study was to review the design methods that have been used to create peptides for use in caries management. Two independent researchers systematically reviewed many in vitro studies in which peptides were designed for use in caries management. They assessed the risk of bias in the included studies. This review identified 3592 publications, of which 62 were selected. Forty-seven studies reported 57 antimicrobial peptides. Among them, 31 studies (66%, 31/47) used the template-based design method; 9 studies (19%, 9/47) used the conjugation method; and 7 studies (15%, 7/47) used other methods, such as the synthetic combinatorial technology method, the de novo design method and cyclisation. Ten studies reported mineralising peptides. Seven of these (70%, 7/10) used the template-based design method, two (20%, 2/10) used the de novo design method, and one study (10%, 1/10) used the conjugation method. In addition, five studies developed their own peptides with antimicrobial and mineralising properties. These studies used the conjugation method. Our assessment for the risk of bias in the 62 reviewed studies showed that 44 publications (71%, 44/62) had a medium risk and that 3 publications had a low risk (5%, 3/62). The two most common methods for developing peptides for use in caries management that were used in these studies were the template-based design method and the conjugation method. Full article
(This article belongs to the Special Issue Microbial Resistance Mechanisms)
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