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Microorganisms
Special Issues
Exploration of Intrinsic Resistance in Bacteria
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Exploration of Intrinsic Resistance in Bacteria

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 7739

Special Issue Editor

Dr. Lia Danelishvili

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA
Interests: Mycobacterium tuberculous; non-tuberculous mycobacteria (NTM); virulence; host–pathogen interaction; innate immunity; persistence; response to antibiotics; intrinsic resistance; drug discovery; bacteriophages

Special Issue Information

Dear Colleagues,

Bacterial pathogens have evolved innate strategies that enable genetically susceptible pathogen to resist killing by lethal doses of clinically available antibiotics. Intrinsic resistance is a major contributing factor for the development of persistent, chronic, and drug-resistant infections in clinics. Therefore, it is critical to identify and characterize origins of intrinsic resistance and to understand molecular mechanisms including the metabolic transition of the pathogen and the host environmental factors stimulating the antibiotic tolerance state in bacteria. Such knowledge is essential for advancements in new treatment interventions through targeting the virulence factors of intrinsic resistance and, subsequently, inhibiting mechanisms that lead to the development of drug resistance.

This research topic encourages original research articles, brief research reports, perspective, opinion articles and reviews laying foundation into the deep understanding of bacterial inherent mechanisms promoting the antimicrobial resistance and demonstrating innovative treatment strategies that can potentially increase the therapeutic efficacy of existing antibiotics.

Dr. Lia Danelishvili
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. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • infectious diseases
  • bacterial pathogens
  • microbial tolerance
  • antibiotic resistance
  • persistent infections
  • efflux and influx systems
  • cell wall permeability
  • bacterial metabolism
  • growth and metabolic rate
  • omics data
  • bacterial proteome
  • new therapeutic strategies
  • metabolism-based strategies
  • metabolites to overcome antibiotic tolerance
  • biofilm
  • host environmental stresses
  • hypoxia

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Published Papers (2 papers)

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Research

23 pages, 3433 KiB  
Article
Role of the Spore Coat Proteins CotA and CotB, and the Spore Surface Protein CDIF630_02480, on the Surface Distribution of Exosporium Proteins in Clostridioides difficile 630 Spores
by Nicolás Montes-Bravo, Alba Romero-Rodríguez, José García-Yunge, César Medina, Marjorie Pizarro-Guajardo and Daniel Paredes-Sabja
Microorganisms 2022, 10(10), 1918; https://doi.org/10.3390/microorganisms10101918 - 27 Sep 2022
Cited by 2 | Viewed by 2746
Abstract
Clostridioides difficile is Gram-positive spore-former bacterium and the leading cause of nosocomial antibiotic-associated diarrhea. During disease, C. difficile forms metabolically dormant spores that persist in the host and contribute to recurrence of the disease. The outermost surface of C. difficile spores, termed the [...] Read more.
Clostridioides difficile is Gram-positive spore-former bacterium and the leading cause of nosocomial antibiotic-associated diarrhea. During disease, C. difficile forms metabolically dormant spores that persist in the host and contribute to recurrence of the disease. The outermost surface of C. difficile spores, termed the exosporium, plays an essential role in interactions with host surfaces and the immune system. The main exosporium proteins identified to date include three orthologues of the BclA family of collagen-like proteins, and three cysteine-rich proteins. However, how the underlying spore coat influences exosporium assembly remains unclear. In this work, we explore the contribution of spore coat proteins cotA and cotB, and the spore surface protein, CDIF630_02480, to the exosporium ultrastructure, formation of the polar appendage and the surface accessibility of exosporium proteins. Transmission electron micrographs of spores of insertional inactivation mutants demonstrate that while cotB contributes to the formation of thick-exosporium spores, cotA and CDIF630_02480 contribute to maintain proper thickness of the spore coat and exosporium layers, respectively. The effect of the absence of cotA, cotB and CDIF630_02480 on the surface accessibility of the exosporium proteins CdeA, CdeC, CdeM, BclA2 and BclA3 to antibodies was affected by the presence of the spore appendage, suggesting that different mechanisms of assembly of the exosporium layer might be implicated in each spore phenotype. Collectively, this work contributes to our understanding of the associations between spore coat and exosporium proteins, and how these associations affect the assembly of the spore outer layers. These results have implications for the development of anti-infecting agents targeting C. difficile spores. Full article
(This article belongs to the Special Issue Exploration of Intrinsic Resistance in Bacteria)
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19 pages, 1444 KiB  
Article
Mycobacterium abscessus Genetic Determinants Associated with the Intrinsic Resistance to Antibiotics
by Mylene Gorzynski, Tiana Week, Tiana Jaramillo, Elizaveta Dzalamidze and Lia Danelishvili
Microorganisms 2021, 9(12), 2527; https://doi.org/10.3390/microorganisms9122527 - 7 Dec 2021
Cited by 13 | Viewed by 3985
Abstract
Mycobacterium abscessus subsp. abscessus (MAB) is a fast-growing nontuberculous mycobacterium causing pulmonary infections in immunocompromised and immunocompetent individuals. The treatment of MAB infections in clinics is extremely challenging, as this organism is naturally resistant to most available antibiotics. There is limited knowledge on [...] Read more.
Mycobacterium abscessus subsp. abscessus (MAB) is a fast-growing nontuberculous mycobacterium causing pulmonary infections in immunocompromised and immunocompetent individuals. The treatment of MAB infections in clinics is extremely challenging, as this organism is naturally resistant to most available antibiotics. There is limited knowledge on the mechanisms of MAB intrinsic resistance and on the genes that are involved in the tolerance to antimicrobials. To identify the MAB genetic factors, including the components of the cell surface transport systems related to the efflux pumps, major known elements contributing to antibiotic resistance, we screened the MAB transposon library of 2000 gene knockout mutants. The library was exposed at either minimal inhibitory (MIC) or bactericidal concentrations (BC) of amikacin, clarithromycin, or cefoxitin, and MAB susceptibility was determined through the optical density. The 98 susceptible and 36 resistant mutants that exhibited sensitivity below the MIC and resistance to BC, respectively, to all three drugs were sequenced, and 16 mutants were found to belong to surface transport systems, such as the efflux pumps, porins, and carrier membrane enzymes associated with different types of molecule transport. To establish the relevance of the identified transport systems to antibiotic tolerance, the gene expression levels of the export related genes were evaluated in nine MAB clinical isolates in the presence or absence of antibiotics. The selected mutants were also evaluated for their ability to form biofilms and for their intracellular survival in human macrophages. In this study, we identified numerous MAB genes that play an important role in the intrinsic mechanisms to antimicrobials and further demonstrated that, by targeting components of the drug efflux system, we can significantly increase the efficacy of the current antibiotics. Full article
(This article belongs to the Special Issue Exploration of Intrinsic Resistance in Bacteria)
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