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Microorganisms
Special Issues
Mechanisms of Antimicrobial Resistance in Bacterial Pathogens
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Mechanisms of Antimicrobial Resistance in Bacterial Pathogens

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

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 5398

Special Issue Editor

Dr. Bindu Subhadra

E-Mail Website
Guest Editor
College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA
Interests: gene regulation; multidrug efflux pumps; quorum sensing; biofilms; virulence; pathogenesis; sRNA regulation; infectious diseases; carbohydrate metabolism; biocompatibility of biomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bacterial pathogens employ several mechanisms to resist antimicrobials, and these include reducing the uptake of drugs, inactivating drugs, modifying drug targets, and the active efflux of drugs. Limiting the uptake of drugs is facilitated by reducing the permeability of the outer membrane. Drug inactivation is carried out via the actual degradation of a drug or via modifying a drug through the addition of chemical groups. There are multiple components in the bacterial cell that are targets of antimicrobial agents, and these targets are modified by bacteria to increase drug resistance. Bacteria also possess efflux pumps, which are either constitutively expressed or induced under certain environmental stimuli. Gram-negative bacteria express a plethora of efflux pumps that enable them to survive at higher antibiotic concentrations via exporting compounds from cells, thereby reducing the antibiotic concentrations to subtoxic levels. Antimicrobial resistance is a major crisis worldwide and is one of the serious threats faced by mankind. Thus, in this Special Issue, we would like to present the up-to-date knowledge on the various mechanisms of antimicrobial resistance, giving emphasis to multidrug efflux pumps, their control, and recent advances in the development of efflux pump inhibitors with which to tackle multidrug resistance in bacterial pathogens. This Special Issue could serve as a basis for the discovery of potential antimicrobial therapeutics based on inhibiting various mechanisms of antimicrobial resistance, with which highly resistant bacterial pathogens can be controlled.

The topics that are covered by this Special Issue include, but are not limited to, the following:

  • Antimicrobial resistance;
  • Mechanisms of antimicrobial resistance;
  • Multidrug efflux pumps;
  • Transcriptional regulation of efflux pumps;
  • Uptake of drugs;
  • Inactivation of drugs;
  • Modification of drug targets;
  • RND transporters;
  • Efflux pump inhibitors;
  • Antimicrobial therapeutics.

Dr. Bindu Subhadra
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

  • multidrug efflux pumps 
  • antibiotic resistance 
  • transcriptional regulation of efflux pumps 
  • drug transport 
  • RND transporters 
  • efflux pump inhibitors 
  • antimicrobial therapeutics

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Published Papers (3 papers)

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Research

15 pages, 769 KiB  
Article
Extended-Spectrum Beta-Lactamase- and Plasmidic AmpC-Producing Enterobacterales among the Faecal Samples in the Bulgarian Community
by Petya Stankova, Lyudmila Boyanova, Daniela Atanasova, Sashka Mihaylova, Mariya Sredkova, Raina Gergova, Kalina Mihova and Rumyana Markovska
Microorganisms 2024, 12(9), 1777; https://doi.org/10.3390/microorganisms12091777 - 28 Aug 2024
Viewed by 741
Abstract
The aim of the present work was to genetically characterise cefotaxime-resistant enterobacteria isolated from community carriers in Bulgaria. In total, 717 faecal samples from children and adults in five medical centres in Sofia, Pleven and Burgas were examined. Antimicrobial susceptibility was evaluated by [...] Read more.
The aim of the present work was to genetically characterise cefotaxime-resistant enterobacteria isolated from community carriers in Bulgaria. In total, 717 faecal samples from children and adults in five medical centres in Sofia, Pleven and Burgas were examined. Antimicrobial susceptibility was evaluated by the disk diffusion method. blaESBL or plasmidic AmpC (pAmpC) genes were detected by PCR and sequencing. MLST and ERIC-PCR were used to detect clonal relatedness. Among the faecal samples, 140 cefotaxime-resistant enterobacteria were found. The most frequently detected species was Escherichia coli (77.9%, 109/140 samples), followed by Klebsiella pneumoniae (7.9%, 11/140). Among the isolates, blaCTX-M-15 (37.1%) was predominant, followed by blaCTX-M-3 (19.2%), blaCTX-M-14 (10%), and blaCTX-M-27 (4.3 %). Genes encoding pAmpC were observed in 11.4% (blaDHA-1, 16/140) and in 1.4% (blaCMY-2, 2/140). The frequency of ESBL and pAmpC producers among the subjects was 14.6% and 2.5%, respectively. No carbapenem-resistant isolates were found. Four main clonal complexes (CC131, CC10, CC38, and CC155) were detected among E. coli isolates. The most common type was ST131, phylogroup B2 (16.5%). The increased frequency of ESBL- and pAmpC-producing enterobacteria in the community is a prerequisite for treatment failures of the associated infections and a good background for further studies. Full article
(This article belongs to the Special Issue Mechanisms of Antimicrobial Resistance in Bacterial Pathogens)
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20 pages, 2152 KiB  
Article
Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes
by María Pérez-Vázquez, Carla López-Causapé, Andrés Corral-Lugo, Michael J. McConnell, Jesús Oteo-Iglesias, Antonio Oliver and Antonio J. Martín-Galiano
Microorganisms 2023, 11(10), 2486; https://doi.org/10.3390/microorganisms11102486 - 4 Oct 2023
Viewed by 1658
Abstract
Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have [...] Read more.
Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance. Full article
(This article belongs to the Special Issue Mechanisms of Antimicrobial Resistance in Bacterial Pathogens)
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16 pages, 11060 KiB  
Article
Antibacterial Properties of Methanolic Leaf Extracts of Melia azedarach L. against Gram-Positive and Gram-Negative Pathogenic Bacteria
by Soraya Naila Touzout, Abderrahmen Merghni, Aicha Laouani, Halima Boukhibar, Rawaf Alenazy, Abdulmohsen Alobaid, Mustafa Alenazy, Mossadok Ben-Attia, Khaled Saguem and Safia El-Bok
Microorganisms 2023, 11(8), 2062; https://doi.org/10.3390/microorganisms11082062 - 11 Aug 2023
Cited by 3 | Viewed by 2133
Abstract
Melia azedarach L., a Meliaceae family tree, is widely used in traditional folkloric medicine for its pharmaceutical properties. In the present study, we investigated the phytochemical composition of four methanolic leaf extracts of M. azedarach of various origins (Algeria and Tunisia) using high-performance [...] Read more.
Melia azedarach L., a Meliaceae family tree, is widely used in traditional folkloric medicine for its pharmaceutical properties. In the present study, we investigated the phytochemical composition of four methanolic leaf extracts of M. azedarach of various origins (Algeria and Tunisia) using high-performance liquid chromatography (HPLC). The antibacterial efficacy and mechanisms of action against Gram-positive and Gram-negative pathogenic microorganisms were then evaluated. Our findings revealed a presence of phenolic acids and flavonoids, such as gallic acid, chlorogenic acid, caffeic acid, hyperoside, isoquercetin, quercetin, and isorhamnetin both in Algerian and Tunisian localities, with an abundance of phenolic acids compared to flavonoids. Additionally, the studied extracts exhibit a broad spectrum of antibacterial activities, with MIC values ranging from 31.25 mg/mL to 125 mg/mL. Methanolic leaf extracts of M. azedarach from Algeria exhibited more potent biofilm eradication, with a percentage of inhibition reaching 72.17% against the S. aureus strain. Furthermore, inhibitory concentrations of tested substances, particularly the extract from the Relizane area, were capable of disrupting the membrane integrity of the treated bacteria as well as producing oxidative stress through ROS generation. Likewise, our results reveal that plant extract induces lipid peroxidation by raising MDA levels in comparison to untreated cells, particularly with the plant extract of Blida. M. azedarach extracts also reduced the synthesis of antioxidant enzymes (CAT and SOD). Our findings illustrate that M. azedarach remains a plant with significant antibacterial potential and distinct mechanisms of action that are closely related to the origins of this specimen. Full article
(This article belongs to the Special Issue Mechanisms of Antimicrobial Resistance in Bacterial Pathogens)
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