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Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with...
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Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 12659

Special Issue Editor

Prof. Dr. Haihua Liang

E-Mail Website
Guest Editor
School of Medicine, Southern University of Science and Technology, Shenzhen, China
Interests: microbial functional genomics; pathogenicity and drug resistance mechanisms of pathogens; development of new antibacterial drugs

Special Issue Information

Dear Colleagues,

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infections requiring ventilation, such as COVID-19. P. aeruginosa is also a model bacterium widely used in all biological areas.

In addition to continued, intense efforts to understand the bacterial pathogenesis of P. aeruginosa, including virulence factors (LPS, quorum sensing, two-component systems, six-type secretion systems, outer membrane vesicles (OMVs), CRISPR-Cas and their regulation, etc.), rapid progress has been made in terms of further studying host–pathogen interaction, particularly host immune networks involving autophagy, inflammasome, non-coding RNAs, cGAS, etc. Furthermore, numerous technologic advances, such as bioinformatics, metabolomics, scRNA-seq, nanoparticles, drug screening, and phage therapy, have been used to improve our understanding of P. aeruginosa pathogenesis and host defense.

Nevertheless, much information remains to be uncovered about the interactions between P. aeruginosa and host immune responses, including the mechanisms of drug resistance by known or unannotated bacterial virulence factors, as well as mammalian cell signaling pathways. The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections, especially those caused by multi-drug resistance strains. We have benefited from advancements in research tools and technology, as dissecting this pathogen’s features has led to novel molecular and mechanistic insights, as well as improved dynamic and holistic perspectives on these strains. 

Understanding its pathogenicity, drug resistance mechanisms, and interaction with its host is crucial for developing effective strategies to combat P. aeruginosa infections and mitigate their impacts on human health.

Prof. Dr. Haihua Liang
Guest Editor

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Keywords

  • Pseudomonas aeruginosa (P. aeruginosa)
  • virulence factor
  • pathogenesis
  • host defense patterns
  • immune evasion
  • inflammatory response
  • antibiotic/drug resistance
  • therapeutic targets and strategies

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Published Papers (5 papers)

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Research

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10 pages, 6022 KiB  
Article
The Challenging Life of Mutators: How Pseudomonas aeruginosa Survives between Persistence and Evolution in Cystic Fibrosis Lung
by Martina Rossitto, Valeria Fox, Gianluca Vrenna, Vanessa Tuccio Guarna Assanti, Nour Essa, Maria Stefania Lepanto, Serena Raimondi, Marilena Agosta, Venere Cortazzo, Vanessa Fini, Annarita Granaglia, Enza Montemitro, Renato Cutrera, Carlo Federico Perno and Paola Bernaschi
Microorganisms 2024, 12(10), 2051; https://doi.org/10.3390/microorganisms12102051 - 11 Oct 2024
Cited by 1 | Viewed by 1472
Abstract
Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair [...] Read more.
Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF P. aeruginosa isolates. We selected 609 isolates from 51 patients with CF chronically colonised by P. aeruginosa to study, by full-length genome sequencing, the longitudinal evolution of the bacterium. We recovered at least one hypermutable (mutator) isolate in 57% of patients. By combining genomic information and phenotypic analyses, we followed the evolutionary pathways of the P. aeruginosa mutator strains, identifying their contribution to multi-drug resistance and the emergence of new sub-lineages. By implementing patient clinical data, we observed that mutators preferentially follow a specific evolutionary trajectory in patients with a negative clinical outcome and that maintenance antibiotic polytherapy, based on alternating molecules, apparently reduces the occurrence of hypermutability. Finally, we draw attention to the possibility that modulator-induced changes in the pulmonary environment may be associated with the onset of hypermutability. Full article
(This article belongs to the Special Issue Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host)
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34 pages, 3568 KiB  
Article
Insights on Pseudomonas aeruginosa Carbohydrate Binding from Profiles of Cystic Fibrosis Isolates Using Multivalent Fluorescent Glycopolymers Bearing Pendant Monosaccharides
by Deborah L. Chance, Wei Wang, James K. Waters and Thomas P. Mawhinney
Microorganisms 2024, 12(4), 801; https://doi.org/10.3390/microorganisms12040801 - 16 Apr 2024
Viewed by 2970
Abstract
Pseudomonas aeruginosa contributes to frequent, persistent, and, often, polymicrobial respiratory tract infections for individuals with cystic fibrosis (CF). Chronic CF infections lead to bronchiectasis and a shortened lifespan. P. aeruginosa expresses numerous adhesins, including lectins known to bind the epithelial cell and mucin [...] Read more.
Pseudomonas aeruginosa contributes to frequent, persistent, and, often, polymicrobial respiratory tract infections for individuals with cystic fibrosis (CF). Chronic CF infections lead to bronchiectasis and a shortened lifespan. P. aeruginosa expresses numerous adhesins, including lectins known to bind the epithelial cell and mucin glycoconjugates. Blocking carbohydrate-mediated host–pathogen and intra-biofilm interactions critical to the initiation and perpetuation of colonization offer promise as anti-infective treatment strategies. To inform anti-adhesion therapies, we profiled the monosaccharide binding of P. aeruginosa from CF and non-CF sources, and assessed whether specific bacterial phenotypic characteristics affected carbohydrate-binding patterns. Focusing at the cellular level, microscopic and spectrofluorometric tools permitted the solution-phase analysis of P. aeruginosa binding to a panel of fluorescent glycopolymers possessing distinct pendant monosaccharides. All P. aeruginosa demonstrated significant binding to glycopolymers specific for α-D-galactose, β-D-N-acetylgalactosamine, and β-D-galactose-3-sulfate. In each culture, a small subpopulation accounted for the binding. The carbohydrate anomeric configuration and sulfate ester presence markedly influenced binding. While this opportunistic pathogen from CF hosts presented with various colony morphologies and physiological activities, no phenotypic, physiological, or structural feature predicted enhanced or diminished monosaccharide binding. Important to anti-adhesive therapeutic strategies, these findings suggest that, regardless of phenotype or clinical source, P. aeruginosa maintain a small subpopulation that may readily associate with specific configurations of specific monosaccharides. This report provides insights into whole-cell P. aeruginosa carbohydrate-binding profiles and into the context within which successful anti-adhesive and/or anti-virulence anti-infective agents for CF must contend. Full article
(This article belongs to the Special Issue Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host)
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15 pages, 2497 KiB  
Article
High-Throughput Short Sequence Typing Schemes for Pseudomonas aeruginosa and Stenotrophomonas maltophilia Pure Culture and Environmental DNA
by Thibault Bourdin, Marie-Ève Benoit, Emilie Bédard, Michèle Prévost, Caroline Quach, Eric Déziel and Philippe Constant
Microorganisms 2024, 12(1), 48; https://doi.org/10.3390/microorganisms12010048 - 27 Dec 2023
Cited by 2 | Viewed by 1679
Abstract
Molecular typing techniques are utilized to determine genetic similarities between bacterial isolates. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been fully explored. This work reports the development and validation of two high-throughput [...] Read more.
Molecular typing techniques are utilized to determine genetic similarities between bacterial isolates. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been fully explored. This work reports the development and validation of two high-throughput short sequence typing (HiSST) schemes targeting the opportunistic pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia, along with a modified SM2I selective medium for the specific isolation of S. maltophilia. These HiSST schemes are based on four discriminative loci for each species and demonstrate high discriminating power, comparable to pairwise whole-genome comparisons. Each scheme includes species-specific PCR primers for precise differentiation from closely related taxa, without the need for upstream culture-dependent methods. For example, the primers targeting the bvgS locus make it possible to distinguish P. aeruginosa from the very closely related Pseudomonas paraeruginosa sp. nov. The selected loci included in the schemes are adapted to massive parallel amplicon sequencing technology. An R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analyses for efficient and accurate genotyping of P. aeruginosa and S. maltophilia. We demonstrate the performance of both schemes through in silico validations, assessments against reference culture collections, and a case study involving environmental samples. Full article
(This article belongs to the Special Issue Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host)
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14 pages, 3231 KiB  
Article
Taxifolin as a Metallo-β-Lactamase Inhibitor in Combination with Augmentin against Verona Imipenemase 2 Expressing Pseudomonas aeruginosa
by Bogdan M. Benin, Trae Hillyer, Aylin S. Crugnale, Andrew Fulk, Caitlyn A. Thomas, Michael W. Crowder, Matthew A. Smith and Woo Shik Shin
Microorganisms 2023, 11(11), 2653; https://doi.org/10.3390/microorganisms11112653 - 28 Oct 2023
Cited by 2 | Viewed by 1842
Abstract
Among the various mechanisms that bacteria use to develop antibiotic resistance, the multiple expression of β-lactamases is particularly problematic, threatening public health and increasing patient mortality rates. Even if a combination therapy—in which a β-lactamase inhibitor is administered together with a β-lactam antibiotic—has [...] Read more.
Among the various mechanisms that bacteria use to develop antibiotic resistance, the multiple expression of β-lactamases is particularly problematic, threatening public health and increasing patient mortality rates. Even if a combination therapy—in which a β-lactamase inhibitor is administered together with a β-lactam antibiotic—has proven effective against serine-β-lactamases, there are no currently approved metallo-β-lactamase inhibitors. Herein, we demonstrate that quercetin and its analogs are promising starting points for the further development of safe and effective metallo-β-lactamase inhibitors. Through a combined computational and in vitro approach, taxifolin was found to inhibit VIM-2 expressing P. aeruginosa cell proliferation at <4 μg/mL as part of a triple combination with amoxicillin and clavulanate. Furthermore, we tested this combination in mice with abrasive skin infections. Together, these results demonstrate that flavonol compounds, such as taxifolin, may be developed into effective metallo-β-lactamase inhibitors. Full article
(This article belongs to the Special Issue Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host)
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Review

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21 pages, 1782 KiB  
Review
Innovative Antibiotic Therapies for Carbapenem-Resistant Gram-Negative Bacterial Infections: Clinical Efficacy, Safety, and Comparative Studies
by Majid Eslami, Amirabbas Safaripour, Seyedeh Zahra Banihashemian, Sahar Nikjoo Niaragh, Mohammad Amin Hemmati, Arefeh Shojaeian, Setayesh Fakhariyan, Atiye Rabbani and Valentyn Oksenych
Microorganisms 2025, 13(2), 295; https://doi.org/10.3390/microorganisms13020295 - 29 Jan 2025
Viewed by 1618
Abstract
This review provides an overview of recent research and advancements in infection prevention and the treatment of drug-resistant bacterial diseases. Cefiderocol, a novel siderophore cephalosporin, has demonstrated effectiveness against carbapenem-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical trials, including APEKS-NP [...] Read more.
This review provides an overview of recent research and advancements in infection prevention and the treatment of drug-resistant bacterial diseases. Cefiderocol, a novel siderophore cephalosporin, has demonstrated effectiveness against carbapenem-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical trials, including APEKS-NP and CREDIBLE-CR, affirm its efficacy for hospital-acquired pneumonia (HAP) but highlight concerns over increased mortality due to severe renal complications. Cefiderocol has shown superior outcomes in complicated urinary tract infections (cUTI) compared to imipenem–cilastatin. A comparison of colistin monotherapy versus combination therapy with meropenem for carbapenem-resistant infections revealed no significant improvement in clinical outcomes with combination therapy but noted delays in resistance development. Colistin–rifampicin combination therapy showed potential benefits for colistin-resistant Acinetobacter baumannii, although results were not statistically significant. SPR206, a polymyxin derivative, and durlobactam, a β-lactamase inhibitor, show promise in addressing these resistant strains, with durlobactam demonstrating efficacy in combination with sulbactam and imipenem–cilastatin. Additional studies investigated antibiotic strategies for resistant infections, including cefoperazone–sulbactam versus combination therapy with tigecycline, and examined infection-prevention strategies in surgical settings, comparing chlorhexidine–alcohol and povidone–iodine. This research highlights the importance of optimizing treatment regimens and infection-control measures across various healthcare settings, including neonatology and surgical care. Full article
(This article belongs to the Special Issue Pseudomonas aeruginosa: Pathogenicity, Drug Resistance Mechanisms and Interaction with the Host)
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