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Emerging Microbes & Infections Dec 2021Biofilm formation and the appearance of persister cells with low metabolic rates are key factors affecting conventional treatment failure and antibiotic resistance....
Biofilm formation and the appearance of persister cells with low metabolic rates are key factors affecting conventional treatment failure and antibiotic resistance. Using impedance-based measurements, crystal violet staining and traditional culture we have studied the biofilm growth dynamics of 13 strains under the effect of seven conventional antibiotics. Real-time growth quantifications revealed that the exposure of established biofilms to certain concentrations of ciprofloxacin, ceftazidime and tobramycin induced the emergence of persister cells, that showed different morphology and pigmentation, as well increased antibiotic resistance. Whole-genome sequencing of wildtype and persister cells identified several SNPs, a genomic inversion and a genomic duplication in one of the strains. However, these mutations were not uniquely associated with persisters, suggesting that the persistent phenotype may be related to metabolic and transcriptional changes. Given that mannitol has been proposed to activate bacterial metabolism, the synergistic combination of mannitol and ciprofloxacin was evaluated on clinical 48 h biofilms. When administered at doses ≥320 mg/L, mannitol was capable of preventing persister cell formation by efficiently activating dormant bacteria and making them susceptible to the antibiotic. These results were confirmed using viable colony counting. As the tested ciprofloxacin-mannitol combination appeared to fully eradicate mature biofilms, we conclude that impedance-based biofilm diagnostics, which permits antibiotic susceptibility testing and the identification of persister cells, is of great potential for the clinical practice and could aid in establishing treatment breakpoints for emerging biofilm-related infections.
Topics: Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Humans; Microbial Sensitivity Tests; Microbial Viability; Mutation; Polymorphism, Single Nucleotide; Pseudomonas Infections; Pseudomonas aeruginosa; Staining and Labeling
PubMed: 34663186
DOI: 10.1080/22221751.2021.1994355 -
Toxins Sep 2020is the most common human opportunistic pathogen associated with nosocomial diseases. In 2017, the World Health Organization has classified as a critical agent... (Review)
Review
is the most common human opportunistic pathogen associated with nosocomial diseases. In 2017, the World Health Organization has classified as a critical agent threatening human health, and for which the development of new treatments is urgently necessary. One interesting avenue is to target virulence factors to understand pathogenicity. Thus, characterising exoproteins of is a hot research topic and proteomics is a powerful approach that provides important information to gain insights on bacterial virulence. The aim of this review is to focus on the contribution of proteomics to the studies of exoproteins, highlighting its relevance in the discovery of virulence factors, post-translational modifications on exoproteins and host-pathogen relationships.
Topics: Bacterial Proteins; Host-Pathogen Interactions; Protein Processing, Post-Translational; Proteome; Proteomics; Pseudomonas aeruginosa; Virulence; Virulence Factors
PubMed: 32899849
DOI: 10.3390/toxins12090571 -
Brazilian Journal of Microbiology :... Mar 2021Due to the severity of infections caused by P. aeruginosa and the limitations in treatment, it is necessary to find new therapeutic alternatives. Thus, the use of silver... (Review)
Review
Due to the severity of infections caused by P. aeruginosa and the limitations in treatment, it is necessary to find new therapeutic alternatives. Thus, the use of silver nanoparticles (AgNPs) is a viable alternative because of their potential actions in the combat of microorganisms, showing efficacy against Gram-positive and Gram-negative bacteria, including multidrug-resistant microorganisms (MDR). In this sense, the aim of this work was to conduct a literature review related to the antibacterial and antibiofilm activity of AgNPs against antibiotic-sensitive and multidrug-resistant Pseudomonas aeruginosa strains. The AgNPs are promising for future applications, which may match the clinical need for effective antibiotic therapy. The size of AgNPs is a crucial element to determine the therapeutic activity of nanoparticles, since smaller particles present a larger surface area of contact with the microorganism, affecting their vital functioning. AgNPs adhere to the cytoplasmic membrane and cell wall of microorganisms, causing disruption, penetrating the cell, interacting with cellular structures and biomolecules, and inducing the generation of reactive oxygen species and free radicals. Studies describe the antimicrobial activity of AgNPs at minimum inhibitory concentration (MIC) between 1 and 200 μg/mL against susceptible and MDR P. aeruginosa strains. These studies have also shown antibiofilm activity through disruption of biofilm structure, and oxidative stress, inhibiting biofilm growth at concentrations between 1 and 600 μg/mL of AgNPs. This study evidences the advance of AgNPs as an antibacterial and antibiofilm agent against Pseudomonas aeruginosa strains, demonstrating to be an extremely promising approach to the development of new antimicrobial systems.
Topics: Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Humans; Metal Nanoparticles; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Silver
PubMed: 33231865
DOI: 10.1007/s42770-020-00406-x -
Current Opinion in Microbiology Feb 2020Chronic infections often contain complex polymicrobial communities that are recalcitrant to antibiotic treatment. The pathogens associated with these infectious... (Review)
Review
Chronic infections often contain complex polymicrobial communities that are recalcitrant to antibiotic treatment. The pathogens associated with these infectious communities are often studied in pure culture for their ability to cause disease. However, recent studies have begun to focus on the role of polymicrobial interactions in disease outcomes. Pseudomonas aeruginosa can colonize patients with chronic lung diseases for years and sometimes even decades. During these prolonged infections, P. aeruginosa encounters a plethora of other microbes including bacteria, fungi, and viruses. The interactions between these microbes can vary greatly, ranging from antagonistic to synergistic depending on specific host and microbe-associated contexts. These additional layers of complexity associated with chronic P. aeruginosa infections must be considered in future studies in order to fully understand the physiology of infection. Such studies focusing on the entire infectious community rather than individual species may ultimately lead to more effective therapeutic design for persistent polymicrobial infections.
Topics: Animals; Bacteria; Humans; Lung; Lung Diseases; Microbial Interactions; Microbiota; Pseudomonas aeruginosa
PubMed: 32062024
DOI: 10.1016/j.mib.2020.01.014 -
Journal of Microbiology (Seoul, Korea) Jul 2018Bacterial biofilms remain a persistent threat to human healthcare due to their role in the development of antimicrobial resistance. To combat multi-drug resistant... (Review)
Review
Bacterial biofilms remain a persistent threat to human healthcare due to their role in the development of antimicrobial resistance. To combat multi-drug resistant pathogens, it is crucial to enhance our understanding of not only the regulation of biofilm formation, but also its contribution to bacterial virulence. Iron acquisition lies at the crux of these two subjects. In this review, we discuss the role of iron acquisition in biofilm formation and how hosts impede this mechanism to defend against pathogens. We also discuss recent findings that suggest that biofilm formation can also have the reciprocal effect, influencing siderophore production and iron sequestration.
Topics: Animals; Biofilms; Cystic Fibrosis; Host-Pathogen Interactions; Humans; Iron; Mice; Polysaccharides, Bacterial; Pseudomonas aeruginosa; Siderophores; Virulence Factors
PubMed: 29948830
DOI: 10.1007/s12275-018-8114-3 -
FEMS Immunology and Medical Microbiology Aug 2010We review the recent advances in the understanding of the Pseudomonas aeruginosa biofilm lifestyle from studies using in vitro laboratory setups such as flow chambers... (Review)
Review
We review the recent advances in the understanding of the Pseudomonas aeruginosa biofilm lifestyle from studies using in vitro laboratory setups such as flow chambers and microtiter trays. Recent work sheds light on the role of nutrients, motility, and quorum sensing in structure formation in P. aeruginosa biofilms. The second messenger, c-di-GMP, is established as an important regulator of the synthesis of polysaccharide and protein components of the biofilm matrix. Extracellular DNA is shown to be an essential component of the biofilm matrix. It has become apparent that biofilm formation involves interactions between different subpopulations. The molecular mechanisms underlying the tolerance of biofilm bacteria to antimicrobial agents are beginning to be unraveled, and new knowledge has been obtained regarding the environmental cues and regulatory mechanisms involved in biofilm dispersal.
Topics: Anti-Bacterial Agents; Biofilms; DNA, Bacterial; Polysaccharides, Bacterial; Pseudomonas aeruginosa
PubMed: 20497222
DOI: 10.1111/j.1574-695X.2010.00690.x -
Journal of Bacteriology Oct 2021Pseudomonas aeruginosa strains PA14 and PAO1 are among the two best-characterized model organisms used to study the mechanisms of biofilm formation while also...
Pseudomonas aeruginosa strains PA14 and PAO1 are among the two best-characterized model organisms used to study the mechanisms of biofilm formation while also representing two distinct lineages of P. aeruginosa. Previous work has shown that PA14 and PAO1 use different strategies for surface colonization; they also have different extracellular matrix composition and different propensities to disperse from biofilms back into the planktonic phase surrounding them. We expand on this work here by exploring the consequences of these different biofilm production strategies during direct competition. Using differentially labeled strains and microfluidic culture methods, we show that PAO1 can outcompete PA14 in direct competition during early colonization and subsequent biofilm growth, that they can do so in constant and perturbed environments, and that this advantage is specific to biofilm growth and requires production of the Psl polysaccharide. In contrast, P. aeruginosa PA14 is better able to invade preformed biofilms and is more inclined to remain surface-associated under starvation conditions. These data together suggest that while P. aeruginosa PAO1 and PA14 are both able to effectively colonize surfaces, they do so in different ways that are advantageous under different environmental settings. Recent studies indicate that P. aeruginosa PAO1 and PA14 use distinct strategies to initiate biofilm formation. We investigated whether their respective colonization and matrix secretion strategies impact their ability to compete under different biofilm-forming regimes. Our work shows that these different strategies do indeed impact how these strains fair in direct competition: PAO1 dominates during colonization of a naive surface, while PA14 is more effective in colonizing a preformed biofilm. These data suggest that even for very similar microbes there can be distinct strategies to successfully colonize and persist on surfaces during the biofilm life cycle.
Topics: Biofilms; Cell Death; Lab-On-A-Chip Devices; Pseudomonas aeruginosa; Surface Properties
PubMed: 34516283
DOI: 10.1128/JB.00265-21 -
Clinical Microbiology and Infection :... Mar 2020Pseudomonas aeruginosa is one of the most common pathogens isolated from respiratory tract specimen in patients with bronchiectasis. It is considered highly responsible... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pseudomonas aeruginosa is one of the most common pathogens isolated from respiratory tract specimen in patients with bronchiectasis. It is considered highly responsible for pathogenicity, progression and clinical outcomes of bronchiectasis.
AIMS
To summarize existing evidence on how different factors of Pseudomonas aeruginosa affect the pathogenicity, progression and clinical outcomes of bronchiectasis, so as to provide possible insights for clinical practice and related research in the future.
SOURCES
PubMed was searched for studies pertaining to bronchiectasis and P. aeruginosa published to date, with no specific inclusion or exclusion criteria. Reference lists of retrieved reviews were searched for additional articles.
CONTENT
This review focused on non-cystic fibrosis bronchiectasis and also provided some data on cystic fibrosis when studies in bronchiectasis were limited. We discussed various factors in relation to P. aeruginosa: virulence factors, drug resistance, regulatory systems, genomic diversity and transmission of P. aeruginosa, as well as treatment for P. aeruginosa. Their impacts on bronchiectasis and its management were discussed.
IMPLICATIONS
The impact of P. aeruginosa on bronchiectasis is definite, although conclusions in some aspects are still vague. Faced with the worrying drug-resistance status and treatment bottleneck, individualized management and novel therapies beyond the classic pathway are most likely to be a future trend. To confirm the independent or integrated impact of various factors of P. aeruginosa on bronchiectasis and to figure out all the problems mentioned, larger randomized control trials are truly needed in the future.
Topics: Anti-Bacterial Agents; Bronchiectasis; Clinical Decision-Making; Disease Management; Disease Progression; Disease Susceptibility; Drug Resistance, Bacterial; Genetic Variation; Genome, Bacterial; Humans; Patient Outcome Assessment; Pseudomonas Infections; Pseudomonas aeruginosa; Virulence Factors
PubMed: 31306794
DOI: 10.1016/j.cmi.2019.07.010 -
Pathogens and Disease Mar 2015Pseudomonas aeruginosa is one of the most intractable human pathogens that pose serious clinical challenge due to extensive prevalence of multidrug-resistant clinical... (Review)
Review
Pseudomonas aeruginosa is one of the most intractable human pathogens that pose serious clinical challenge due to extensive prevalence of multidrug-resistant clinical isolates. Armed with abundant virulence and antibiotic resistance mechanisms, it is a major etiologic agent in a number of acute and chronic infections. A complex and intricate network of regulators dictates the expression of pathogenicity factors in P. aeruginosa. Some proteins within the network play key roles and control multiple pathways. This review discusses the role of one such protein, AmpR, which was initially recognized for its role in antibiotic resistance by regulating AmpC β-lactamase. Recent genomic, proteomic and phenotypic analyses demonstrate that AmpR regulates expression of hundreds of genes that are involved in diverse pathways such as β-lactam and non-β-lactam resistance, quorum sensing and associated virulence phenotypes, protein phosphorylation, and physiological processes. Finally, ampR mutations in clinical isolates are reviewed to shed light on important residues required for its function in antibiotic resistance. The prevalence and evolutionary implications of AmpR in pathogenic and nonpathogenic proteobacteria are also discussed. A comprehensive understanding of proteins at nodal positions in the P. aeruginosa regulatory network is crucial in understanding, and ultimately targeting, the pathogenic stratagems of this organism.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Pseudomonas aeruginosa; Regulon
PubMed: 25066236
DOI: 10.1111/2049-632X.12208 -
International Journal of Molecular... Oct 2021is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased... (Comparative Study)
Comparative Study
is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased morbidity and mortality rate. The natural resistance in these organisms is caused by the production of specific enzymes and biofilm formation, while acquired resistance is multifactorial. Precise recognition of potential antibiotic resistance on different molecular levels is essential. Metabolomics tools may aid in the observation of the flux of low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. In this study, the metabolisms of two strains were compared-antibiotic susceptible vs. resistant. Analysis was performed on both intra- and extracellular metabolites. The H NMR method was used together with multivariate and univariate data analysis, additionally analysis of the metabolic pathways with the FELLA package was performed. The results revealed the differences in metabolism of drug-resistant and drug-susceptible strains and provided direct molecular information about response for different types of antibiotics. The most significant differences were found in the turnover of amino acids. This study can be a valuable source of information to complement research on drug resistance in .
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Metabolome; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 34639158
DOI: 10.3390/ijms221910820