Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication.

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique. This USFD dry powder is designed to efficiently deliver muco-inert Cipro-Col-Lips to the lungs. Once deposited, the liposomes rapidly diffuse into the airway mucus, reaching the biofilm sites. The muco-inert Cipro-Col-Lips neutralize the biofilm-secreted toxins and simultaneously trigger the release of their therapeutic payload, exerting a synergistic antibiofilm effect. Our results demonstrated that the optimal USFD liposomal dry powder formulation exhibited satisfactory in vitro aerosol performance in terms of fine particle fraction (FPF) of 44.44 ± 0.78 %, mass median aerodynamic diameter (MMAD) of 4.27 ± 0.21 µm, and emitted dose (ED) of 99.31 ± 3.31 %. The muco-inert Cipro-Col-Lips effectively penetrate the airway mucus and accumulate at the biofilm site, neutralizing toxins and safeguarding lung cells. The triggered release of ciprofloxacin and colistin works synergistically to reduce the biofilm's antibiotic resistance, impede the development of antibiotic resistance, and eliminate 99.99 % of biofilm-embedded bacteria, including persister bacteria. Using a PA-beads induced biofilm-associated lung infection mouse model, the in vivo efficacy of this liposomal dry powder aerosol was tested, and the results demonstrated that this liposomal dry powder aerosol achieved a 99.7 % reduction in bacterial colonization, and significantly mitigated inflammation and pulmonary fibrosis. The USFD dry powder inhalation containing muco-inert Cipro-Col-Lips emerges as a promising therapeutic strategy for treating PA biofilm-associated lung infections.

Dual roles of the conditional extracellular vesicles derived from Pseudomonas aeruginosa biofilms: Promoting and inhibiting bacterial biofilm growth.

Antibiotic-resistant biofilm infections have emerged as public health concerns because of their enhanced tolerance to high-dose antibiotic treatments. The biofilm life cycle involves multiple developmental stages, which are tightly regulated by active cell-cell communication via specific extracellular signal messengers such as extracellular vesicles. This study was aimed at exploring the roles of extracellular vesicles secreted by Pseudomonas aeruginosa at different developmental stages in controlling biofilm growth. Our results show that extracellular vesicles secreted by P. aeruginosa biofilms during their exponential growth phase (G-EVs) enhance biofilm growth. In contrast, extracellular vesicles secreted by P. aeruginosa biofilms during their death/survival phase (D-EVs) can effectively inhibit/eliminate P. aeruginosa PAO1 biofilms up to 4.8-log10 CFU/cm2. The inhibition effectiveness of D-EVs against P. aeruginosa biofilms grown for 96 h improved further in the presence of 10-50 µM Fe3+ ions. Proteomic analysis suggests the inhibition involves an iron-dependent ferroptosis mechanism. This study is the first to report the functional role of bacterial extracellular vesicles in bacterial growth, which depends on the developmental stage of the parent bacteria. The finding of D-EV-activated ferroptosis-based bacterial death may have significant implications for preventing antibiotic resistance in biofilms.

Eradication of Pseudomonas aeruginosa biofilm using quercetin-mediated copper oxide nanoparticles incorporated in the electrospun polycaprolactone nanofibrous scaffold.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that form biofilms in chronic wounds and is difficult to treat with standard treatment methods. In the present study, flavonoid quercetin-mediated CuONPs (Que-CuONPs) were successfully synthesized and incorporated in the electrospun polycaprolactone (Que-CuONPs-PCL) nanofibrous membrane to eradicate the burn wound infection causing P. aeruginosa biofilm. The fabricated scaffold Que-CuONPs-PCL was characterized using HR-SEM, EDX, XRD, and FTIR. The synthesized Que-CuONPs appeared as spherical in shape with the average size of 36 nm. The crystallite size of the synthesized CuONPs was calculated as 23 nm. Antibacterial activity results shows that the ZOI and MIC of Que-CuONPs against P. aeruginosa was found to be 20 mm and 5 µg/mL, respectively. Antibiofilm assay results indicate the pre-formed P. aeruginosa biofilm was completely eradicated by Que-CuONPs at 8-MIC. The Que-CuONPs-PCL nanofibrous scaffolds exhibits less cytotoxic effects on mouse fibroblast (L929) cells. Finally, this study highlights the fabricated Que-CuONPs-PCL nanofibrous scaffolds exhibits an excellent antibiofilm effect against P. aeruginosa biofilm with a great biocompatibility.

Insights into the Influence of Signal Peptide on the Enzymatic Properties of Alginate Lyase AlyI1 with Removal Effect on Pseudomonas aeruginosa Biofilm.

Most reports on signal peptides focus on their ability to affect the normal folding of proteins, thereby affecting their secreted expression, while few studies on its effects on enzymatic properties were published. Therefore, biochemical characterization and comparison of alginate lyase rALYI1/rALYI1-1 (rALYI1: without signal peptides; rALYI1-1:with signal peptides) were conducted in our study, and the results showed that the signal peptide affected the biochemical properties, especially in temperature and pH. rALYI1 (32.15 kDa) belonging to polysaccharide lyase family 7 was cloned from sea-cucumber-gut bacterium Tamlana sp. I1. The optimum temperature of both rALYI1 and rALYI1-1 was 40 °C, but the former had a wider optimum temperature range and better thermal stability. The optimum pH of rALYI1 and rALYI1-1 were 7.6 and 8.6, respectively. The former was more stable and acid resistant. Noticeably, rALYI1 was a salt-activated enzyme and displayed remarkable salt tolerance. Alginate, an essential polysaccharide in algae and Pseudomonas aeruginosa biofilms, is composed of α-L-guluronate and ß-D-mannuronate. It is also found in our study that rALYI1 is also effective in removing mature biofilms compared with controls. In conclusion, the signal peptide affects several biochemical properties of the enzyme, and alginate lyase rALYI1 may be an effective method for inhibiting biofilm formation of Pseudomonas aeruginosa.

Evaluating Bacterial Pathogenesis Using a Model of Human Airway Organoids Infected with Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is one of the leading invasive agents of human pulmonary infection, especially in patients with compromised immunity. Prior studies have used various in vitro models to establish P. aeruginosa infection and to analyze transcriptomic profiles of either the host or pathogen, and yet how much those works are relevant to the genuine human airway still raises doubts. In this study, we cultured and differentiated human airway organoids (HAOs) that recapitulate, to a large extent, the histological and physiological features of the native human mucociliary epithelium. HAOs were then employed as a host model to monitor P. aeruginosa biofilm development. Through dual-species transcriptome sequencing (RNA-seq) analyses, we found that quorum sensing (QS) and several associated protein secretion systems were significantly upregulated in HAO-associated bacteria. Cocultures of HAOs and QS-defective mutants further validated the role of QS in the maintenance of a robust biofilm and disruption of host tissue. Simultaneously, the expression magnitude of multiple inflammation-associated signaling pathways was higher in the QS mutant-infected HAOs, suggesting that QS promotes immune evasion at the transcriptional level. Altogether, modeling infection of HAOs by P. aeruginosa captured several crucial facets in host responses and bacterial pathogenesis, with QS being the most dominant virulence pathway showing profound effects on both bacterial biofilm and host immune responses. Our results revealed that HAOs are an optimal model for studying the interaction between the airway epithelium and bacterial pathogens. IMPORTANCE Human airway organoids (HAOs) are an organotypic model of human airway mucociliary epithelium. The HAOs can closely resemble their origin organ in terms of epithelium architecture and physiological function. Accumulating studies have revealed the great values of the HAO cultures in host-pathogen interaction research. In this study, HAOs were used as a host model to grow Pseudomonas aeruginosa biofilm, which is one of the most common pathogens found in pulmonary infection cases. Dual transcriptome sequencing (RNA-seq) analyses showed that the cocultures have changed the gene expression pattern of both sides significantly and simultaneously. Bacterial quorum sensing (QS), the most upregulated pathway, contributed greatly to biofilm formation, disruption of barrier function, and subversion of host immune responses. Our study therefore provides a global insight into the transcriptomic responses of both P. aeruginosa and human airway epithelium.

Enhanced Eradication of Mucin-Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers.

Bacterial biofilm-related infections are difficult to eradicate and require repeated treatments with high doses of antibiotics. Thus, there is an urgent need for new treatment strategies that minimize the use of antibiotics while enhancing biofilm eradication. Functionalized reservoir-based microdevices, such as, microcontainers (MCs), offer, high drug loading capacity, mucus embedment, and tuneable drug release. Here, MCs are loaded with the antibiotic ciprofloxacin (CIP), and sealed with a lid consisting of chitosan (CHI) and a mucolytic agent, N-acetylcysteine (NAC). It is found that CHI and NAC work synergistically, showing improved mucoadhesive and mucolytic properties. To better mimic the in vivo habitat of Pseudomonas aeruginosa (P. aeruginosa), the biofilm is grown in a mucin-containing medium on a newly developed centrifugal microfluidic system. The CHI/NAC coated MCs improve eradication of biofilm (88.22 ± 2.89%) compared to CHI-coated MCs (72.68 ± 3.73%) or bolus injection (39.86 ± 13.28%). The findings suggest that MCs are significantly more efficient than a bolus treatment. Furthermore, CHI/NAC functionalized MCs kill most of the biomass already after 5 h (80.75 ± 3.50%), mainly due to a fast drug release. This is the first time that CHI/NAC has been combined as a coating to explore mucolytic properties on bacterial biofilms.

Prevalence of the Genes Associated with Biofilm and Toxins Synthesis amongst the Pseudomonas aeruginosa Clinical Strains.

Pseudomonas aeruginosa is one of the most commonly isolated bacteria from clinical specimens, with an increasing isolation frequency in nosocomial outbreaks. The hypothesis tested was whether carbapenem-resistant P. aeruginosa strains display an altered carriage of the virulence factor genes, depending on the type of carbapenem resistance. The aim of the study was to investigate, by PCR, the frequency of 10 chosen virulence factors genes (phzM, phzS, exoT, exoY, exoU, toxA, exoS, algD, pilA and pilB) and the genotype distribution in 107 non-duplicated carbapenem-resistant P. aeruginosa isolates. P. aeruginosa genes involved in phenazine dyes and exoenzyme T synthesis were noted with the highest frequency (100%). Fimbriae-encoding genes were detected with the lowest incidence: 15.9% and 4.7% for pilin A and B, respectively. The differences observed between the exoS gene prevalence amongst the carbapenemase-positive and the carbapenemase-negative strains and the pilA gene prevalence amongst the strains of different origins were statistically significant. Virulence genes' prevalence and the genotype distribution vary amongst P. aeruginosa strains resistant to carbapenems, especially in terms of their carbapenemase synthesis ability and the strain origin.

Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies.

In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute to chronic infection. To form aggregates, P. aeruginosa can use different mechanisms, each with its own pathogenic implications. However, how they form in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix that holds the aggregates together. Pel and Psl exopolysaccharides are structural and protective components of this matrix. We develop an immunohistochemical method to visualize Pel and Psl in CF sputum. We demonstrate that both exopolysaccharides are expressed in the CF airways and that the morphology of aggregates is consistent with an exopolysaccharide-dependent aggregation mechanism. We reason that the cationic exopolysaccharide Pel may interact with some of the abundant anionic host polymers in sputum. We show that Pel binds extracellular DNA (eDNA) and that this interaction likely impacts current therapies by increasing antimicrobial tolerance and protecting eDNA from digestion.

The ß-Lactamase Inhibitor Boronic Acid Derivative SM23 as a New Anti-Pseudomonas aeruginosa Biofilm.

Pseudomonas aeruginosa is a Gram-negative nosocomial pathogen, often causative agent of severe device-related infections, given its great capacity to form biofilm. P. aeruginosa finely regulates the expression of numerous virulence factors, including biofilm production, by Quorum Sensing (QS), a cell-to-cell communication mechanism used by many bacteria. Selective inhibition of QS-controlled pathogenicity without affecting bacterial growth may represent a novel promising strategy to overcome the well-known and widespread drug resistance of P. aeruginosa. In this study, we investigated the effects of SM23, a boronic acid derivate specifically designed as ß-lactamase inhibitor, on biofilm formation and virulence factors production by P. aeruginosa. Our results indicated that SM23: (1) inhibited biofilm development and production of several virulence factors, such as pyoverdine, elastase, and pyocyanin, without affecting bacterial growth; (2) decreased the levels of 3-oxo-C12-HSL and C4-HSL, two QS-related autoinducer molecules, in line with a dampened lasR/lasI system; (3) failed to bind to bacterial cells that had been preincubated with P. aeruginosa-conditioned medium; and (4) reduced both biofilm formation and pyoverdine production by P. aeruginosa onto endotracheal tubes, as assessed by a new in vitro model closely mimicking clinical settings. Taken together, our results indicate that, besides inhibiting ß-lactamase, SM23 can also act as powerful inhibitor of P. aeruginosa biofilm, suggesting that it may have a potential application in the prevention and treatment of biofilm-associated P. aeruginosa infections.

Global trends of Pseudomonas aeruginosa biofilm research in the past two decades: A bibliometric study.

Pseudomonas aeruginosa biofilm formation is a primary cause of chronic infections. This has been a highly active area of research over the past two decades due to causing high mortality risks in immunocompromised patients. This study evaluates global trends in the dynamic and rapidly evolving field of P. aeruginosa biofilm research through bibliometric and visualized analyses. Publications from 1994 to 2018 on P. aeruginosa biofilm research were retrieved from Web of Science, Scopus, and PubMed, and their bibliometric data were systematically studied. The VOSviewer software was used to conduct global analyses of bibliographic coupling, coauthorship, cocitation, and co-occurrence. A total of 9,527 publications were included in this study. The overall number of publications and research interest in the field displayed a strongly rising trend. The USA made the greatest contributions to the field, with the highest h-index and number of citations compared with other countries, while Denmark had the highest average citation per publication. The Journal of Bacteriology had the highest number of publications in the field, while the University of Copenhagen was the institution with the highest contribution influence. Co-occurrence network maps revealed that the most prominent topics in P. aeruginosa biofilm research were mechanistic studies, in vitro/in vivo studies, and biofilm formation studies. Pseudomonas aeruginosa biofilms constitute a dynamic research area in microbiology with increasing global research interest. Future studies will likely focus on investigating the mechanisms of biofilm formation to solve infection-associated clinical problems.

Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of Antibiotics into Pseudomonas aeruginosa Biofilms in Lungs.

Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic-co-glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method. The interactions of the nanoparticles with the biological barriers were comprehensively investigated by using cutting-edge techniques (e.g., quartz crystal microbalance with dissipation monitoring, total internal reflection fluorescence microscopy-based particle tracking, in vitro biofilm model cultured in a flow-chamber system, and quantitative imaging analysis). Our results suggest that the mucus-inert, enzymatically cleavable TPGS shell enables the nanoparticles to penetrate through the mucus, accumulate in the deeper layer of the biofilms, and serve as sustained release depot, thereby improving the killing efficacy of azithromycin (a macrolide antibiotic) against biofilm-forming Pseudomonas aeruginosa. In conclusion, the ultrasmall TPGS-PLGA hybrid nanoparticles represent an efficient delivery system to overcome the multiple barriers and release antibiotics in a sustained manner in the vicinity of the biofilm-forming bacteria.

A short peptide with selective anti-biofilm activity against Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacteria.

Biofilm-related infections represent an enormous clinical challenge nowadays. In this context, diverse studies are underway to develop effective antimicrobial agents targeting bacterial biofilms. Here, we describe the antibacterial and anti-biofilm activities of a short, cationic peptide named R5F5, obtained from sliding-window analysis based on a peptide (PcDBS1R5) derived from Plasmodium chabaudi. Ten fragments were generated (R5F1 to F10) and submitted to initial antibacterial assays against Pseudomonas aeruginosa. As a result, R5F5 showed the highest antimicrobial activity. We therefore carried out further antibacterial and anti-biofilm assays against P. aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacterial strains. R5F5 revealed selective anti-biofilm activity, as the peptide inhibited >60% biofilm formation in all cases from 8 to 64 µg·mL-1. Moreover, R5F5 was not hemolytic against mice erythrocytes at 640 µg mL-1. Cytotoxic effects on human lung fibroblast cells were not detected at 160 µg·mL-1. Structural studies revealed that R5F5 presents random coil conformations in water and 50% 2,2,2-trifluoroethanol (TFE)/water (v/v), whereas amphipathic, extended conformations were observed in contact with sodium dodecyl sulfate (SDS) micelles. Thus, here we report a novel peptide with selective anti-biofilm activity against susceptible and resistant bacterial strains, with no toxicity toward mammalian cells and that adopts a stable structure in anionic environment.

Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor.

Biofilm-infected wounds are clinically challenging. Vascular endothelial growth factor and host defence S100A8/A9 are crucial for wound healing but may be suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm infection was compared in central and peripheral zones of burn-wounded, infection-susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB/c wounds but increased peripheral levels 4-7 days post-infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central, but inducing peripheral, vascular endothelial growth factor levels and reducing host response in wounds of BALB/c mice. This suppression is detrimental to the resolution of biofilm-infected necrosis.

Morphological bactericidal fast-acting effects of peracetic acid, a high-level disinfectant, against Staphylococcus aureus and Pseudomonas aeruginosa biofilms in tubing.

Background: The bactericidal effect of disinfectants against biofilms is essential to reduce potential endoscopy-related infections caused by contamination. Here, we investigated the bactericidal effect of a high-level disinfectant, peracetic acid (PAA), against Staphylococcus aureus and Pseudomonas aeruginosa biofilm models in vitro. Methods: S. aureus and P. aeruginosa biofilms were cultured at 35 °C for 7 days with catheter tubes. The following high-level disinfectants (HLDs) were tested: 0.3% PAA, 0.55% ortho-phthalaldehyde (OPA), and 2.0% alkaline-buffered glutaraldehyde (GA). Biofilms were exposed to these agents for 1-60 min and observed after 5 min and 30 min by transmission and scanning electron microscopy. A Student's t test was performed to compare the exposure time required for bactericidal effectiveness of the disinfectants. Results: PAA and GA were active within 1 min and 5 min, respectively, against S. aureus and P. aeruginosa biofilms. OPA took longer than 10 min and 30 min to act against S. aureus and P. aeruginosa biofilms, respectively (p < 0.01). Treatment with PAA elicited changes in cell shape after 5 min and structural damage after 30 min. Conclusions: Amongst the HLDs investigated, PAA elicited the most rapid bactericidal effects against both biofilms. Additionally, treatment with PAA induced morphological alterations in the in vitro biofilm models, suggesting that PAA exerts fast-acting bactericidal effects against biofilms associated with endoscopy-related infections. These findings indicate that the exposure time for bactericidal effectiveness of HLDs for endoscope reprocessing in healthcare settings should be reconsidered.

Eradication of P. aeruginosa biofilm in endotracheal tubes based on lock therapy: results from an in vitro study.

BACKGROUND: Despite the several strategies available for the management of biofilm-associated ventilator-associated pneumonia, data regarding the efficacy of applying antibiotics to the subglottic space (SS) are scarce. We created an in vitro model to assess the efficacy of antibiotic lock therapy (ALT) applied in the SS for eradication of Pseudomonas aeruginosa biofilm in endotracheal tubes (ETTs). METHODS: We applied 2 h of ALT to a P. aeruginosa biofilm in ETTs using a single dose (SD) and a 5-day therapy model (5D). We used sterile saline lock therapy (SLT) as the positive control. We compared colony count and the percentage of live cells between both models. RESULTS: The median (IQR) cfu counts/ml and percentage of live cells in the SD-ALT and SD-SLT groups were, respectively, 3.12 × 105 (9.7 × 104-0) vs. 8.16 × 107 (7.0 × 107-0) (p = 0.05) and 53.2% (50.9%-57.2%) vs. 91.5% (87.3%-93.9%) (p < 0.001). The median (IQR) cfu counts/ml and percentage of live cells in the 5D-ALT and 5D-SLT groups were, respectively, 0 (0-0) vs. 3.2 × 107 (2.32 × 107-0) (p = 0.03) and 40.6% (36.6%-60.0%) vs. 90.3% (84.8%-93.9%) (p < 0.001). CONCLUSION: We demonstrated a statistically significant decrease in the viability of P. aeruginosa biofilm after application of 5D-ALT in the SS. Future clinical studies to assess ALT in patients under mechanical ventilation are needed.

Chronic Pseudomonas aeruginosa biofilm infection impairs murine S100A8/A9 and neutrophil effector cytokines-implications for delayed wound closure?

The impact of Pseudomonas aeruginosa biofilm infections in chronic wounds and clinical implication for healing is receiving increased attention. However, the pathophysiology of host/pathogen interplay is not fully understood. By further revealing the mechanisms, necessary new treatment strategies may be identified. Since the background for chronic wounds is diverse, representative animal models are important. We assessed host response and spontaneous wound closure in the relatively resistant C3H/HeN and the susceptible BALB/c mouse strain. Full-thickness burn wounds were inflicted in 108 mice. Pseudomonas aeruginosa biofilm (106 colony forming units) was injected subcutaneously in 72 mice, euthanised day 4, 7 or 10 days post-infection. Wounds were analysed for neutrophil host response markers: S100A8/A9, keratinocyte-derived chemokine and granulocyte-colony stimulating factor. Total peripheral blood leucocyte and polymorphonuclear count were assessed in parallel. Histopathology evaluated wound inflammatory burden. Photoplanimetry described macroscopical wound closure. Stable chronic wound infection was established in all challenged mice. Pseudomonas aeruginosa biofilm suppressed neutrophil host response in wounds. C3H/HeN mice achieved earlier systemic inflammatory control and healed faster than BALB/c mice. Pseudomonas aeruginosa biofilms perturb host defence thereby inducing a steady state of chronic infection which may impair wound healing. These results indicate therapeutic options for immune modulation of biofilm-infected wounds.

Nontoxic Cationic Coumarin Polyester Coatings Prevent Pseudomonas aeruginosa Biofilm Formation.

The rapid increase in bacterial infections and antimicrobial resistance is a growing public health concern. Infections arising from bacterial contamination of surgical tools, medical implants, catheters, and hospital surfaces can potentially be addressed by antimicrobial polymeric coatings. The challenge in developing such polymers for in vivo use is the ability to achieve high antimicrobial efficacy while at the same time being nontoxic to human cells. Although several classes of antimicrobial polymers have been developed, many of them cannot be used in the clinical setting due to their nonselective toxicity toward bacteria and mammalian cells. Here, we demonstrate that coumarin polyesters with cationic pendant groups are very effective against Gram negative Pseudomonas aeruginosa. Coumarin polyesters with pendant cationic amine groups were coated onto glass coverslips and tested for their antimicrobial activity against P. aeruginosa colonization of the surface. The results demonstrate that the cationic coumarin polyester kills the surface attached bacterial cells preventing biofilm formation but does not show any hemolytic activity or discernible toxicity toward mammalian cells. The antimicrobial polyesters described in this work have several advantages desired in antimicrobial coatings such as high antimicrobial activity, low toxicity toward mammalian cells, visualization and ease of synthesis and fabrication, all of which are necessary for translation to the clinic.