The filamentous basidiomycete Ceriporia lacerata, an agent of white rot on wood, has never been reported in human disease and its clinical significance is not yet known. We describe 4 patients with respiratory diseases where C. lacerata was implicated in a wide spectrum of clinical manifestations ranging from saprobic colonization to fungal pneumonia. The isolates did not show the morphological characteristics that facilitate recognition of filamentous basidiomycetes, such as the presence of clamp connections, spicules along hyphae, or fruiting bodies. The identity of the mold was confirmed by sequencing the internal transcribed spacer 1 and 4 (ITS-1 and ITS-4) and D1/D2 regions of the rRNA gene. All of the isolates exhibited the lowest MICs of posaconazole and isavuconazole (MIC range, 0.06 to 0.125 μg/ml), followed by itraconazole (MIC range, 0.06 to 0.5 μg/ml), voriconazole (MIC range, 0.125 to 0.5 μg/ml), and amphotericin B (MIC range, 0.25 to 1 μg/ml). The infections reported here occurred in patients with preexisting lung damage induced by tuberculosis or chronic obstructive pulmonary disease. Chronic, sometimes fatal infections by the ascomycete Aspergillus fumigatus and the basidiomycete Schizophyllum commune are well established in the presence of an anatomical pulmonary defect or in the background of immunodeficiency. It is postulated that C. lacerata, a novel opportunist basidiomycete, may be involved in similar pathological processes.
Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant healthcare burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work demonstrated that Pseudomonas aeruginosa (PAO1) biofilmchallenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2 day old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm-challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks; 64% of the biofilm-challenged wounds healed by 6 weeks; and all of the biofilm-challenged wounds healed by 8 weeks. During the wound healing process, P. aeruginosa were gradually cleared from the wounds while the presence of S. aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 107
P. aeruginosa, which was 100 fold higher than the counts isolated from wound beds (i.e. 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization and increased inflammatory cytokines. Hypoxia inducible factor (HIF) expression increased 3 fold in 4 week wounds. In summary, our study demonstrates that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than non biofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test anti-biofilm strategies the treatment of chronic wounds.
Pseudomonas aeruginosa; biofilm; wound infection; keratinocytes; inflammatory response; gene expression
Perenniporia species are basidiomycetes, resupinate shelf fungi responsible for white rot decay of wood. Here, we report for the first time an intracavitary pulmonary fungal ball due to a species of Perenniporia that has not been recognized so far as a human pathogen. The fungus was identified by sequencing of the partial ribosomal operon of a culture from a clinical specimen.
Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled “Future Research Directions in Early CF Lung Disease” on September 21–22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene–environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.
cystic fibrosis; airway disease; innate immunity; microbiology; genetics
Cryptosporidium hominis and Cryptosporidium
parvum, which infect humans equally, are genetically/antigenically almost identical. It remains unclear, however, whether infection with C. hominis protects against C. parvum. Gnotobiotic piglets were used to investigate cross-protection. After ≥3 days of recovery from C. hominis infection, the piglets were completely protected against subsequent challenge with C. hominis but only partially against challenge with C. parvum, as compared with age-matched control animals challenged with either species. In conclusion, C. hominis–specific immunity was sufficient to completely protect against challenge with the same species but insufficient to provide the same level of protection against C. parvum.
PLUNC (palate, lung and nasal epithelium clone) protein is an abundant secretory product of epithelia throughout the mammalian conducting airways. Despite its homology with the innate immune defence molecules BPI (bactericidal/permeability-increasing protein) and LBP (lipopolysaccharide-binding protein), it has been difficult to define the functions of PLUNC. Based on its marked hydrophobicity and expression pattern, we hypothesized that PLUNC is an airway surfactant. We found that purified recombinant human PLUNC exhibited potent surfactant activity by several different measures, and experiments with airway epithelial cell lines and primary cultures indicate that native PLUNC makes a significant contribution to the overall surface tension in airway epithelial secretions. Interestingly, we also found that physiologically relevant concentrations of PLUNC-inhibited Pseudomonas aeruginosa biofilm formation in vitro without acting directly as a bactericide. This finding suggests that PLUNC protein may inhibit biofilm formation by airway pathogens, perhaps through its dispersant properties. Our data, along with reports from other groups on activity against some airway pathogens, expand on an emerging picture of PLUNC as a multifunctional protein, which plays a novel role in airway defences at the air/liquid interface.
biofilm; conducting airway; innate immunity; palate; lung and nasal epithelium clone (PLUNC); surfactant
Azole resistance is an emerging problem in Aspergillus which impacts the management of aspergillosis. Here in we report the emergence and clonal spread of resistance to triazoles in environmental Aspergillus fumigatus isolates in India. A total of 44 (7%) A. fumigatus isolates from 24 environmental samples were found to be triazole resistant. The isolation rate of resistant A. fumigatus was highest (33%) from soil of tea gardens followed by soil from flower pots of the hospital garden (20%), soil beneath cotton trees (20%), rice paddy fields (12.3%), air samples of hospital wards (7.6%) and from soil admixed with bird droppings (3.8%). These strains showed cross-resistance to voriconazole, posaconazole, itraconazole and to six triazole fungicides used extensively in agriculture. Our analyses identified that all triazole-resistant strains from India shared the same TR34/L98H mutation in the cyp51 gene. In contrast to the genetic uniformity of azole-resistant strains the azole-susceptible isolates from patients and environments in India were genetically very diverse. All nine loci were highly polymorphic in populations of azole-susceptible isolates from both clinical and environmental samples. Furthermore, all Indian environmental and clinical azole resistant isolates shared the same multilocus microsatellite genotype not found in any other analyzed samples, either from within India or from the Netherlands, France, Germany or China. Our population genetic analyses suggest that the Indian azole-resistant A. fumigatus genotype was likely an extremely adaptive recombinant progeny derived from a cross between an azole-resistant strain migrated from outside of India and a native azole-susceptible strain from within India, followed by mutation and then rapid dispersal through many parts of India. Our results are consistent with the hypothesis that exposure of A. fumigatus to azole fungicides in the environment causes cross-resistance to medical triazoles. The study emphasises the need of continued surveillance of resistance in environmental and clinical A. fumigatus strains.
Herein we report the topochemical modification of polymer surfaces with perfluorinated aromatic azides. The aryl azides, which have quaternary amine or aldehyde functional groups, were linked to the surface of the polymer by UV irradiation. The polymer substrates used in this study were cyclic olefin copolymer (COC) and poly(methylmethacrylate) (PMMA). These substrates were characterized before and after modification, using reflection-absorption infrared spectroscopy (RAIRS), sessile water contact angle measurements, and X-ray photoelectron spectroscopy (XPS). Analysis of the surface confirmed the presence of an aromatic groups with aldehyde or quaternary amine functionality. Enzyme immobilization and patterning onto polymer surfaces were studied using confocal microscopy. Enzymatic digests were carried out on modified probes manufactured from thermoplastic substrates and the resulting peptide analysis was completed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
Costus speciosus Koen. (Keu, Crape ginger), an ornamental plant, widely distributed in India is traditionally used as astringent, aphrodisiac, purgative, anthelmintic, depurative, febrifuge and expectorant. The plant is also used in rheumatism, dropsy, urinary diseases and jaundice. The purpose of this study is to evaluate the anti-arthritic activity of the methanolic extract of the aerial parts of Costus speciosus (CS) in experimental animal models.
Materials and Methods:
The powdered drug was subjected to successive solvent extraction, with solvents in increasing order of polarity to obtain the methanolic extract of the aerial parts of the plant. CS was evaluated for anti-arthritic action by Freund's adjuvant induced arthritis test in adult Albino rats (150-200 gm). Rats were injected 0.1 ml of complete Freund's adjuvant into the planter region of the left hind paw. Statistical analysis was performed using One way analysis of variance (ANOVA) followed by Bonferonni test. P<0.05 was considered statistically significant.
The methanolic extract of CS in doses of 400 and 800 mg/kg showed 75.50% and 68.33% protection against increase in paw edema, respectively. CS showed dose-dependent action in all the experimental models.
The present study indicates that CS has significant anti-arthritic properties.
Arthritis; Costus speciosus; diclofenac sodium; Freund's complete adjuvant; paw volume
Intradural lumbar disc herniation (ILDH) is uncommon pathology. In present report, authors present a case of ILDH associated with dorsal herniation of the cauda equina rootlets in a 30-year-old male laborer who had chronic backache since last two years. To the best of our knowledge we are reporting this for first time. Report demonstrates the natural course of ILDH.
Intradural disc herniation; Duroplasty; Herniated cauda equina rootlets
Hemolytic uremic syndrome (HUS) leading to acute kidney failure, is a condition linked to the production of primarily Shiga toxin 2 (Stx2) by some E. coli serotypes. We have previously shown that Stx2 A subunit-specific human monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit cultured cell death, and protect mice and piglets from fatal Stx2-intoxication. We have also shown that 5H8 blocks binding of Stx2 to its cell-surface receptor globotriaosyl ceramide (Gb3), whereas Stx2 when complexed with 5C12 binds Gb3 with higher affinity than Stx2. The mechanism by which 5C12 neutralizes Stx2 in vitro involves trapping of Stx2 in the recycling endosomes and releasing it into the extracellular environment. Because of the clinical implications associated with the formation of Stx2/antibody complexes and the potential for trapping and clearance through a severely damaged kidney associated with HUS, we investigated the likely site(s) of Stx2/antibody localization and clearance in intoxicated mice treated with antibody or placebo.
Mice were injected with radiolabeled Stx2 (125I-Stx2) 4 hours after administration of 5C12, 5H8, or phosphate buffered saline (PBS) and the sites of localization of labeled Stx2, were investigated 3, 24 and 48 hours later. The liver recorded statistically much higher concentrations of labeled Stx2 for groups receiving 5C12 and 5H8 antibodies after 3, 24 and 48 hours, as compared with the PBS group. In contrast, highest levels of labeled Stx2 were detected in the kidneys of the PBS group at all 3 sampling times. Mice receiving either of the two HuMAbs were fully protected against the lethal effect of Stx2, as compared with the fatal outcome of the control group.
The results suggest that HuMAbs 5C12 and 5H8 promoted hepatic accumulation and presumably clearance of toxin/antibody complexes, significantly diverting Stx2 localization in the kidneys, the target of Stx2 and the cause of HUS. This is in contrast to the fatal outcome of the control group receiving PBS. The results also confirm earlier observations that both HuMAbs are highly and equally protective against Stx2 intoxication in mice.
Shiga toxin; Radiolabel; Antibody; Toxin elimination; Toxin concentration; Pharmacokinetic; Human monoclonal antibody
Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system.
Chronic wounds are a major clinical problem that leads to considerable morbidity and mortality. We hypothesized that an important factor in the failure of chronic wounds to heal was the presence of microbial biofilm resistant to antibiotics and protected from host defenses. A major difficulty in studying chronic wounds is the absence of suitable animal models. The goal of this study was to create a reproducible chronic wound model in diabetic mice by application of bacterial biofilm. Six millimeter punch biopsy wounds were created on the dorsal surface of diabetic (db/db) mice, subsequently challenged with Pseudomonas aeruginosa (PAO1) biofilms two days post-wounding, and covered with semi-occlusive dressings for two weeks. Most of the control wounds were epithelialized by 28 days post-wounding. In contrast, none of biofilm challenged wounds were closed. Histological analysis showed extensive inflammatory cell infiltration, tissue necrosis and epidermal hyperplasia adjacent to challenged wounds- all indicators of an inflammatory non-healing wound. Quantitative cultures and transmission electron microscopy demonstrated that the majority of bacteria were in the scab above the wound bed rather than in the wound tissue. The model was reproducible, allowed localized cutaneous wound infections without high mortality and demonstrated delayed wound healing following biofilm challenge. This model may provide an approach to study the role of microbial biofilms in chronic wounds as well as the effect of specific biofilm therapy on wound healing.
wound matrix; bacteria; scab; immunohistology; electron microscopy
Trauma is the leading nonobstetric cause of maternal death. The worst complication can be fetal compromise that threatens premature labor or even fetal death. We are reporting a case of a 30-year-old primi, short stature woman who had fracture femur with hypovolaemic shock. Managing such trauma complicated by shock in a pregnant patient needs multidisciplinary approach. Clinician team evaluating and coordinating the care of pregnant trauma patient should understand the pathophysiological changes in pregnancy with trauma to manage hypovolaemic shock, related complications, treatment of fracture, and radiation exposure to the fetus. The use of imaging studies, invasive hemodynamics and surgery, if necessary, should be individualized. A clear understanding of fetal viability, physiological changes of pregnancy, and pathophysiology of shock, is mandatory for optimal, maternal functional, and obstetrical outcome.
Fracture femur; ionizing; pregnancy; radiation; trauma
To evaluate the usefulness of conventional spinal surgery as palliative procedure to rehabilitate dorsolumbar injuries in a rural setup.
Materials and Methods:
Twenty-three patients with dorsolumbar spine injury with complete paraplegia were assessed on the clinical and social rehabilitation parameters after surgical stabilization at Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha, India. The study group comprised 21 male and 2 female patients. The dorsolumbar spine injury was fixed by conventional posterior instrumentation using short-segment pedicle screw system and Harrington rod system with or without fusion. Functional and neurologic outcome was recorded in the follow-up period by using Functional Independence Measure and Frankel grade, respectively. Correlation and analysis of results was established statistically.
Functional outcome showed statistically significant improvement. Social cognition was found intact in a significant number of patients.
This study demonstrates the usefulness of conventional instrumentation as palliative surgical approach to stabilize and rehabilitate patients from deprived sector of rural India.
Conventional spinal instrumentation; Palliative care; Rehabilitation; Rural setup; Total traumatic paraplegia
The problems of inflammation and infection as a leading cause of organ dysfunction and failure is a major problem after injury or operations. When systemic inflammatory response syndrome (SIRS) progress to multiple organ failure (MOF), the mortality reach up to 30–80% depending on the number of failed organs. Recent discoveries and improvement in patient care, a reasonable question then arises, are the incidence of MOF decreasing? The literature suggests a decrease in mortality of patients with severe organ failure and a decrease in elective surgical mortality in patients.
This is prospective study of 50 patients who underwent surgical procedure. They were followed up till date of termination with daily SIRS monitoring, development of MODS and MOF. Risk factors for MOF are addressed.
There are total 31 patients who develop SIRS, of whom 7 patients develop severe sepsis and 4 went into MOF.
Early detection of SIRS helps us to prevent multiple organ dysfunction syndrome (MODS)/MOF, leading to lesser hospital stay and better outcome.
SIRS; MODS; MOF
We present a rare case of extramedullary plasmacytoma of the palatine tonsil with cervical lymph node involvement treated by surgical resection. A 58-year-old Caucasian male presented with a solitary 3 cm × 3 cm jugulodigastric lymph node and was found to have an ipsilateral tonsillar swelling. The involved tonsil and lymph node were surgically resected after two inconclusive fine-needle aspirates, and plasmacytoma was confirmed histologically and by immunocytochemistry. Adjuvant radiotherapy was not indicated as adequate resection was achieved at surgery. We also highlight the challenges of diagnosis when fine-needle aspiration is inconclusive and the need for careful planning before surgery.
Alzheimer's disease (AD) is the most common form of dementia that affects several million people worldwide. The major neuropathological hallmarks of AD are the presence of extracellular amyloid plaques that are composed of Aβ40 and Aβ42 and intracellular neurofibrillary tangles (NFT), which is composed of hyperphosphorylated protein Tau. While the amyloid plaques and NFT could define the disease progression involving neuronal loss and dysfunction, significant cognitive decline occurs before their appearance. Although significant advances in neuroimaging techniques provide the structure and physiology of brain of AD cases, the biomarker studies based on cerebrospinal fluid (CSF) and plasma represent the most direct and convenient means to study the disease progression. Biomarkers are useful in detecting the preclinical as well as symptomatic stages of AD. In this paper, we discuss the recent advancements of various biomarkers with particular emphasis on CSF biomarkers for monitoring the early development of AD before significant cognitive dysfunction.
Shiga toxin 2 (Stx2), one of two Stx liberated by Stx-producing Escherichia coli, is composed of an A subunit monomer and a B subunit pentamer, and is directly linked with hemolytic uremic syndrome in children. The pentameric B subunit binds to its cell surface receptor Gb3 for toxin internalization, and the A subunit follows intracellular retrograde transport to the cytosol where its RNA N-glycosidase activity (RNA-NGA) shuts down the protein synthesis, and leads to cell death. The present study investigated the ability of 19 Stx2 A subunit-specific human monoclonal antibodies (HuMAbs) to neutralize the RNA-NGA, and the association this neutralizing activity with protection of HeLa cells and mice against Stx2-induced death.
The HuMAbs that were stronger inhibitors of RNA-NGA were also better at neutralizing Stx2 mediated HeLa cell death, and those that were weaker inhibitors of RNA-NGA activity were also weaker in protecting HeLa cells. These results suggest that the ability of an A subunit-specific antibody to block the RNA-NGA of the toxin is directly related to its ability to neutralize Stx2-mediated HeLa cell death. However, with the exception of the best RNA-NGA blocking antibodies 5C12 and 2F10, the efficacies of antibody neutralization of RNA-NGA of Stx2 did not correlate with their in vivo protective efficacies. The HuMAb 6C3, which neutralized RNA N-glycosidase activity of Stx2 less effectively than the HuMAbs 6D8 and 6B7, protected 100% of the mice against Stx2 challenge at 50 μg/mouse dose. In contrast, the HuMAbs 6D8 and 6B7, which neutralized RNA N-glycosidase activity of Stx2 more effectively than 6C3, protected 20% and 0% mice at that dose, respectively.
The neutralization efficiency of the RNA-NGA of Stx2 by A subunit-specific antibodies correlate strongly with their abilities to protect HeLa cells against Stx2-mediated toxicity but only the strongest RNA-NGA-neutralizing antibodies correlate very well with both protecting HeLa cells and mice against Stx2 challenge.
The PLUNC (“Palate, lung, nasal epithelium clone”) protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP) family. Two members of this family - the bactericidal/permeability increasing protein (BPI) and the lipopolysaccharide binding protein (LBP) - are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways.
Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms , we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model.
Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.
We present a case of a 35 yrs old female who presented with swelling over her forearm. This is a rare case of a giant cell tumour in a nonepiphyseal region.
Case report and presentation of clinical, radiological and histological data on single case of giant cell tumour of diaphysis of radius.
Although age, clinical features and radiological features are helpful, it is still the histology that helps to clinch the diagnosis.
A thorough literature search and an exhaustive online search using various search engines revealed seven reported cases of giant cell tumours in the diaphysis of long bones. We reiterate the fact that irrespective of the location, a giant cell tumour should be diagnosed based on its histology.
A novel antiinfective approach is to exploit stresses already imposed on invading organisms by the in vivo environment. Fe metabolism is a key vulnerability of infecting bacteria because organisms require Fe for growth, and it is critical in the pathogenesis of infections. Furthermore, humans have evolved potent Fe-withholding mechanisms that can block acute infection, prevent biofilm formation leading to chronic infection, and starve bacteria that succeed in infecting the host. Here we investigate a “Trojan horse” strategy that uses the transition metal gallium to disrupt bacterial Fe metabolism and exploit the Fe stress of in vivo environments. Due to its chemical similarity to Fe, Ga can substitute for Fe in many biologic systems and inhibit Fe-dependent processes. We found that Ga inhibits Pseudomonas aeruginosa growth and biofilm formation and kills planktonic and biofilm bacteria in vitro. Ga works in part by decreasing bacterial Fe uptake and by interfering with Fe signaling by the transcriptional regulator pvdS. We also show that Ga is effective in 2 murine lung infection models. These data, along with the fact that Ga is FDA approved (for i.v. administration) and there is the dearth of new antibiotics in development, make Ga a potentially promising new therapeutic for P. aeruginosa infections.
Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave α2,3-linked sialic acids from glycoconjugates. As mucosal surfaces are heavily sialylated, neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors. However, in contrast to neuraminidase produced by the influenza virus, a role for bacterial neuraminidase in pathogenesis has not yet been clearly established. We constructed a mutant of P. aeruginosa PAO1 by deleting the PA2794 neuraminidase locus (Δ2794) and tested its virulence and immunostimulatory capabilities in a mouse model of infection. Although fully virulent when introduced i.p., the Δ2794 mutant was unable to establish respiratory infection by i.n. inoculation. The inability to colonize the respiratory tract correlated with diminished production of biofilm, as assessed by scanning electron microscopy and in vitro assays. The importance of neuraminidase in biofilm production was further demonstrated by showing that viral neuraminidase inhibitors in clinical use blocked P. aeruginosa biofilm production in vitro as well. The P. aeruginosa neuraminidase has a key role in the initial stages of pulmonary infection by targeting bacterial glycoconjugates and contributing to the formation of biofilm. Inhibiting bacterial neuraminidases could provide a novel mechanism to prevent bacterial pneumonia.