Global Regulatory Pathways Converge To Control Expression of Pseudomonas aeruginosa Type IV Pili

Coggan, Kimberly A.; Higgs, Matthew G.; Brutinel, Evan D.; Marden, Jeremiah N.; Intile, Peter J.; Winther‐Larsen, Hanne C.; Koomey, Michael; Yahr, Timothy L.; Wolfgang, Matthew C.

doi:10.1128/mbio.03696-21

Cited by 8 publications

(8 citation statements)

References 69 publications

(124 reference statements)

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“… 119 , 120 Based on the release kinetics of the drug, a preliminary study of the antibacterial activity was carried out on not treated membranes, testing their ability to inhibit the proliferation of E. coli , S. aureus , and P. aeruginosa , three of the most common bacterial strains accountable for tissue infection and healing failure. 121 − 127 As expected, coaxial membranes showed a lower antibacterial activity with respect to non-coaxial structures, being effective only against S. aureus , but not toward E. coli , which was instead sensitive to Rif no coax . This is due to the significantly higher release of rifampicin from non-coaxial matrices, which may be translated into a major contact with bacteria and a stronger effect.…”

Section: Discussionsupporting

confidence: 62%

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Tuning the Drug Release from Antibacterial Polycaprolactone/Rifampicin-Based Core–Shell Electrospun Membranes: A Proof of Concept

Gruppuso

Guagnini

Musciacchio

et al. 2022

ACS Appl. Mater. Interfaces

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The employment of coaxial fibers for guided tissue regeneration can be extremely advantageous since they allow the functionalization with bioactive compounds to be preserved and released with a long-term efficacy. Antibacterial coaxial membranes based on poly-ε-caprolactone (PCL) and rifampicin (Rif) were synthesized here, by analyzing the effects of loading the drug within the core or on the shell layer with respect to non-coaxial matrices. The membranes were, therefore, characterized for their surface properties in addition to analyzing drug release, antibacterial efficacy, and biocompatibility. The results showed that the lower drug surface density in coaxial fibers hinders the interaction with serum proteins, resulting in a hydrophobic behavior compared to non-coaxial mats. The air-plasma treatment increased their hydrophilicity, although it induced rifampicin degradation. Moreover, the substantially lower release of coaxial fibers influenced the antibacterial efficacy, tested against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Indeed, the coaxial matrices were inhibitory and bactericidal only against S. aureus, while the higher release from non-coaxial mats rendered them active even against E. coli. The biocompatibility of the released rifampicin was assessed too on murine fibroblasts, revealing no cytotoxic effects. Hence, the presented coaxial system should be further optimized to tune the drug release according to the antibacterial effectiveness.

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Section: Discussionsupporting

confidence: 62%

“…aureus, and P. aeruginosa, three of the most common bacterial strains accountable for tissue infection and healing failure. − As expected, coaxial membranes showed a lower antibacterial activity with respect to non-coaxial structures, being effective only against S. aureus, but not toward E.…”

Section: Discussionmentioning

confidence: 52%

Tuning the Drug Release from Antibacterial Polycaprolactone/Rifampicin-Based Core–Shell Electrospun Membranes: A Proof of Concept

Gruppuso

Guagnini

Musciacchio

et al. 2022

ACS Appl. Mater. Interfaces

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“…aeruginosa PAO1 included pilA (the major abundant pilin subunit PilA), fimUpilVWXY1Y2E operon (several less abundant, fiber-associated pilin-like proteins and surface sensor), the pilMNOPQ operon (proteins necessary for assembly and twitching motility), and PilD, the prepilin leader peptidase needed for processing the major and minor pilins [ 57 , 66 , 67 ] were also found. This system is involved in host tissue adherence and colonization and promoting surface-associated twitching motility [ 67 ]. In addition, S3, like PAO1, carried the virulence locus HSI-1 of the type VI secretory system which structurally resembles the contractile tails of bacteriophages [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a hemolytic and antibiotic-resistant Pseudomonas aeruginosa strain S3 pathogenic to fish isolated from Mahananda River in India

Ghosh,

Mangar,

Choudhury

et al. 2024

PLoS ONE

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Virulent strain Pseudomonas aeruginosa isolated from Mahananda River exhibited the highest hemolytic activity and virulence factors and was pathogenic to fish as clinical signs of hemorrhagic spots, loss of scales, and fin erosions were found. S3 was cytotoxic to the human liver cell line (WRL-68) in the trypan blue dye exclusion assay. Genotype characterization using whole genome analysis showed that S3 was similar to P. aeruginosa PAO1. The draft genome sequence had an estimated length of 62,69,783 bp, a GC content of 66.3%, and contained 5916 coding sequences. Eight genes across the genome were predicted to be related to hemolysin action. Antibiotic resistance genes such as class C and class D beta-lactamases, fosA, APH, and catB were detected, along with the strong presence of multiple efflux system genes. This study shows that river water is contaminated by pathogenic P. aeruginosa harboring an array of virulence and antibiotic resistance genes which warrants periodic monitoring to prevent disease outbreaks.

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“…How the bacteria coordinate the Vfr-QS-CRISPR regulatory cascade may depend on the combination of bacterial metabolic requirements and response to environmental factors. Despite the overlapping regulon, the Vfr regulates pili formation (Coggan et al, 2022), which serves as phage binding sites and entry portals for nucleic acid (Craig et al, 2004;Harvey et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The virulence factor regulator and quorum sensing regulate the type I-F CRISPR-Cas mediated horizontal gene transfer in Pseudomonas aeruginosa

et al. 2022

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Pseudomonas aeruginosa is capable of thriving in diverse environments due to its network of regulatory components for effective response to stress factors. The survival of the bacteria is also dependent on the ability to discriminate between the acquisition of beneficial and non-beneficial genetic materials via horizontal gene transfer (HGT). Thus, bacteria have evolved the CRISPR-Cas adaptive immune system for defense against the deleterious effect of phage infection and HGT. By using the transposon mutagenesis approach, we identified the virulence factor regulator (Vfr) as a key regulator of the type I-F CRISPR-Cas system in P. aeruginosa. We showed that Vfr influences the expression of the CRISPR-Cas system through two signaling pathways in response to changes in calcium levels. Under calcium-rich conditions, Vfr indirectly regulates the CRISPR-Cas system via modulation of the AHL-QS gene expression, which could be vital for defense against phage infection at high cell density. When encountering calcium deficiency, however, Vfr can directly regulate the CRISPR-Cas system via a cAMP-dependent pathway. Furthermore, we provide evidence that mutation of vfr reduces the CRISPR-Cas spacer acquisition and interference of HGT. The results from this study add to the regulatory network of factors controlling the CRISPR-Cas system in response to abiotic factors in the environment. The findings may facilitate the design of effective and reliable phage therapies against P. aeruginosa infections, as targeting Vfr could prevent the development of the CRISPR-Cas mediated phage resistance.

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Global Regulatory Pathways Converge To Control Expression of Pseudomonas aeruginosa Type IV Pili

Abstract: Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections. An extensive repertoire of virulence factors aid in P. aeruginosa pathogenesis.

Cited by 8 publications

References 69 publications

Tuning the Drug Release from Antibacterial Polycaprolactone/Rifampicin-Based Core–Shell Electrospun Membranes: A Proof of Concept

Tuning the Drug Release from Antibacterial Polycaprolactone/Rifampicin-Based Core–Shell Electrospun Membranes: A Proof of Concept

Characterization of a hemolytic and antibiotic-resistant Pseudomonas aeruginosa strain S3 pathogenic to fish isolated from Mahananda River in India

The virulence factor regulator and quorum sensing regulate the type I-F CRISPR-Cas mediated horizontal gene transfer in Pseudomonas aeruginosa

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