Pseudomonas aeruginosa reference strains PAO1 and PA14: A genomic, phenotypic, and therapeutic review

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 13, 2022

Pseudomonas aeruginosa is a ubiquitous, motile, gram-negative bacterium that has been recently identified as multi-drug resistant pathogen in critical need of novel therapeutics. Of the approximately 5,000 strains, PAO1 and PA14 are common laboratory reference modeling moderately hyper-virulent phenotypes, respectively. have instrumental facilitating discovery drug targets, testing therapeutics, supplying genomic information on bacterium. While two strains contributed to wide breadth knowledge natural behaviors therapeutic susceptibilities P. aeruginosa, they demonstrated significant deviations from observations human infections. Many these related experimental inconsistencies strain environment complicate and, at times, terminate translation results clinical applications. This review aims provide comparative analysis potential methods improve their relevance.

Language: Английский

---

The Pseudomonas aeruginosa sphBC genes are important for growth in the presence of sphingosine by promoting sphingosine metabolism

Microbiology, Journal Year: 2025, Volume and Issue: 171(1)

Published: Jan. 10, 2025

Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing susceptible bacteria. Pseudomonas aeruginosa is a common opportunistic pathogen that less to sphingosine than many Gram-negative Here, we determined deletion sphBCD operon reduced in presence sphingosine. Using mutants, complementation assays P. PAO1, sphC sphB genes, encoding periplasmic oxidase cytochrome c, respectively, were for on while sphD was dispensable under these conditions. Deletion PA14, protegens Pf-5 fluorescens Pf01 also showed The sphBC genes two other sphingoid phytosphingosine sphinganine. In WT , metabolized an unknown non-inhibitory product, as concentrations drop culture. However, absence accumulates, pointing SphC SphB having role metabolism. Finally, metabolism by protected cells from full public good. This work shows presents novel pathway which bacteria alter host-derived sphingolipids, but it remains open question whether act directly

Language: Английский

---

From the soil to the clinic: the impact of microbial secondary metabolites on antibiotic tolerance and resistance

Nature Reviews Microbiology, Journal Year: 2021, Volume and Issue: 20(3), P. 129 - 142

Published: Sept. 16, 2021

Language: Английский

---

Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112540 - 112540

Published: May 24, 2023

Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently isolated bacterial species from polymicrobial infections of patients with cystic fibrosis chronic wounds. We apply mass spectrometry guided interaction studies to determine how chemical shapes fitness community structure during co-infection these two pathogens. demonstrate that S. is equipped an elegant mechanism inactivate pyochelin via yet uncharacterized methyltransferase Spm (staphylococcal methyltransferase). Methylation abolishes siderophore activity significantly lowers pyochelin-mediated intracellular reactive oxygen (ROS) production in aureus. In a murine wound model, mutant unable methylate shows lower compared its parental strain. Thus, Spm-mediated methylation increase survival vivo competition P. aeruginosa.

Language: Английский

---

Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(4)

Published: Jan. 17, 2023

The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization panel nine–amino acid residue synthetic peptides that display potent antibacterial activity ability disrupt preestablished microbial biofilms. lead peptide (Peptide K6) showed bactericidal against Pseudomonas aeruginosa Staphylococcus aureus in culture monocultures mixed biofilms vitro. Biophysical analysis revealed Peptide K6 self-assembled into nanostructured micelles correlated with its strong antibiofilm activity. When surface displayed on outer membrane protein LamB, two copies were highly Escherichia coli. rapidly increased permeability cells, resistance this toxic occurred less quickly than antibiotic gentamicin. Furthermore, found was safe effective clearing P. aeruginosa–S. mouse model persistent infection. Taken together, properties suggest it promising candidate design additional short form represents worthwhile approach for antimicrobial agents.

Language: Английский

---

DJK-5, an anti-biofilm peptide, increases Staphylococcus aureus sensitivity to colistin killing in co-biofilms with Pseudomonas aeruginosa

npj Biofilms and Microbiomes, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 8, 2025

Chronic infections represent a significant global health and economic challenge. Biofilms, which are bacterial communities encased in an extracellular polysaccharide matrix, contribute to approximately 80% of these infections. In particular, pathogens such as Pseudomonas aeruginosa Staphylococcus aureus frequently co-isolated from the sputum patients with cystic fibrosis commonly found chronic wound Within biofilms, bacteria demonstrate remarkable increase resistance tolerance antimicrobial treatment. We investigated efficacy combining last-line antibiotic colistin membrane- stringent stress response-targeting anti-biofilm peptide DJK-5 against co-biofilms comprised multidrug-resistant P. methicillin-resistant S. (MRSA). Colistin lacks canonical activity aureus. However, our study revealed that under co-biofilm conditions, antibiofilm synergized Similar enhancement was observed when daptomycin, cyclic lipopeptide Gram-positive bacteria, combined DJK-5, resulting increased aeruginosa. The combinatorial treatment induced morphological changes both cell shape size within co-biofilms. Importantly, findings also synergistic murine subcutaneous biofilm-like abscess model. conclusion, treatments or daptomycin show potential for targeting These offer promising avenues developing new therapeutic approaches combat complex

Language: Английский

---

Bacterial species with different nanocolony morphologies have distinct flow-dependent colonization behaviors

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(7)

Published: Feb. 10, 2025

Fluid flows are dominant features of many bacterial environments, and flow can often impact behaviors in unexpected ways. For example, the most common type cardiovascular infection is heart valve colonization by gram-positive bacteria like Staphylococcus aureus Enterococcus faecalis (endocarditis). This behavior counterintuitive because valves experience high shear rates that would naively be expected to reduce colonization. To determine whether these preferentially colonize higher rate we developed a microfluidic system quantify effect conditions on S. E. . We find preferential both species not specific found simple configurations lacking any host factors. enables outcompeted low dominate flow. Surprisingly, experimental computational studies reveal two achieve this via distinct mechanisms. grows cell clusters produces dispersal signal whose transport affected rate. Meanwhile, linear chains mechanical properties result less presence force. In addition establishing divergent mechanisms which each high-flow our findings highlight importance understanding at level collective interactions among cells. These results suggest multicellular nanocolony morphologies have previously unappreciated costs benefits different those introduced fluid

Language: Английский

---

Biofilm Formation by Staphylococcus aureus in the Specific Context of Cystic Fibrosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 597 - 597

Published: Dec. 29, 2022

Staphylococcus aureus is a major human pathogen whose characteristics support its success in various clinical settings including Cystic Fibrosis (CF). In CF, S. indeed the most commonly identified opportunistic children and overall population. colonization/infection, either by methicillin-susceptible or methicillin-resistant strains, will become chronic about one third of CF patients. The persistence patients’ lungs, despite eradication strategies, favored several traits both host pathogen. Among latter, living biofilm highly protective way to survive deleterious environmental conditions, common characteristic shared main pathogens CF. This why has earned status biofilm-associated disease for years now. Biofilm formation aureus, molecular mechanisms governing regulating it, have been extensively studied but received less attention specific context lungs. Here, we review current knowledge on this very context, i.e., importance, study methods, data published mono- multi-species anti-biofilm strategies. focus studies isolates from patients shows that they are still under-represented literature compared with based reference underlines need such studies. Indeed, strains display may not be extrapolated results obtained laboratory strains.

Language: Английский

---

Systematic identification of molecular mediators of interspecies sensing in a community of two frequently coinfecting bacterial pathogens

PLoS Biology, Journal Year: 2022, Volume and Issue: 20(6), P. e3001679 - e3001679

Published: June 21, 2022

Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these is critical for understanding and modulating bacterial behavior natural environments. While responses to foreign species are frequently characterized at phenotypic level, exogenous molecules that elicit understudied. Here, we outline a systematic strategy based on transcriptomics combined with genetic biochemical screens of promoter-reporters identify from one sensed by another. We utilized this method study between pathogens Pseudomonas aeruginosa Staphylococcus aureus found coinfections. discovered P . senses diverse staphylococcal exoproducts including metallophore staphylopine (StP), intermediate metabolites citrate acetoin, multiple modulate its iron starvation response. observed StP inhibits biofilm formation can utilize acetoin growth, revealing have both antagonistic beneficial effects. Due unbiased nature our approach, also identified genome scale genes S affect production each exoproduct, providing possible targets modify community dynamics. Further, combination products recapitulated majority transcriptional response supernatant, validating screening strategy. Cystic fibrosis (CF) clinical isolates showed varying degrees induction or responses, respectively, which suggests widespread among pathogenic strains. Our approach thus secreted physiology, demonstrating efficacy yielding new insight into basis two species.

Language: Английский

---

Bactericidal activity of silver nanoparticles in drug-resistant bacteria

Brazilian Journal of Microbiology, Journal Year: 2023, Volume and Issue: 54(2), P. 691 - 701

Published: May 2, 2023

Language: Английский

---