Antibacterial efficacy of R-type pyocins against Pseudomonas aeruginosa on biofilms and in a murine model of acute lung infection

2020 ◽  
Author(s):  
Mar Redero ◽  
Javier Aznar ◽  
Ana I Prieto
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Murine Model ◽  
Biofilm Formation ◽  
Bacterial Load ◽  
Preventive Treatment ◽  
Lung Infection ◽  
Before And After ◽  
Treatment Alternatives ◽  
Potential Use

Abstract Background The appearance of MDR strains and the development of biofilms make Pseudomonas aeruginosa infections a therapeutic challenge. To overcome this scenario, bacteriocins have been proposed as a potential adjuvant or alternative to antibiotic treatment. Objectives To study the activity of R-pyocins on biofilms and in a murine model of pneumonia using a high-risk clone of P. aeruginosa. Methods The activity of R-pyocins on P. aeruginosa biofilms was tested on bacteria attached to a silicone surface, before and after biofilm formation. The effectiveness of R1-pyocin was studied in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. Results R-pyocins attacked adherent bacteria, preventing biofilm formation, and penetrated into the biofilm, killing P. aeruginosa within it, resulting in a dramatic reduction in bacterial load. R1-pyocin was active in a murine model of P. aeruginosa lung infection, administered before infection as a preventive treatment, and in acute pneumonia, with efficiency higher than standard colistin treatment. In addition, this work is the first to describe histopathological lung changes after administration of R-pyocins, contributing to the resolution of P. aeruginosa pneumonia in a murine model. Conclusions This work highlights the potential use of the R-pyocins as therapeutic agents, alone or as adjuvants, due to its effectiveness on biofilms and in a murine model of pneumonia using ST175, a high-risk clone of P. aeruginosa. It may thus be feasible to consider R-pyocins as a possible therapeutic alternative in XDR infections, where treatment alternatives are limited.

A Bundle of Measures to Control an Outbreak of Pseudomonas aeruginosa Associated With P-Trap Contamination

2018 ◽  
Vol 39 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Houssein Gbaguidi-Haore ◽  
Amélie Varin ◽  
Pascal Cholley ◽  
Michelle Thouverez ◽  
Didier Hocquet ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Bacterial Load ◽  
Tertiary Care ◽  
Multidrug Resistant ◽  
Control Measures ◽  
Pipe System ◽  
Infection Control Measures ◽  
Cross Transmission ◽  
Proactive Measures

OBJECTIVETo describe an outbreak of multidrug-resistant Pseudomonas aeruginosa in which the hospital waste-pipe system was the likely source of contamination and to report the bundle of measures that facilitated the long-term control of the outbreak.DESIGNOutbreak investigation.SETTINGThe hematology unit of a tertiary-care referral center.PATIENTSPatients who were colonized or infected with P. aeruginosa belonging to the clonal outbreak.METHODSPatients admitted to our 15-bed stem-cell transplantation hematology unit were screened for P. aeruginosa carriage. Pseudomonas aeruginosa isolates were also obtained from diagnostic samples. We assessed the microbiological contamination of P-traps, water and toilets for 42 months. Extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) were screened and identified by polymerase chain reaction (PCR) and sequencing. Molecular typing of ESBL- or MBL-producing isolates was carried out using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).RESULTSFrom 2009 to 2013, a biclonal outbreak of IMP-19–producing ST235 (11 cases) and IMP-29–producing ST111 (10 cases) of P. aeruginosa occurred. The environmental investigation strongly suggested that P-traps were the reservoirs for the outbreak strains. A bundle of infection control measures, including engineering interventions on water outlets and disinfection of P-traps, controlled the outbreak.CONCLUSIONSWe report a prolonged outbreak of IMP-producing high-risk clones of P. aeruginosa, for which P-traps seems to play a major role in cross-transmission. It appears essential to implement proactive measures to limit the bacterial load in water fittings of high-risk units.Infect Control Hosp Epidemiol 2018;39:164–169

Mucoid Pseudomonas aeruginosa isolates maintain the biofilm formation capacity and the gene expression profiles during the chronic lung infection of CF patients

Apmis ◽  
2011 ◽  
Vol 119 (4-5) ◽  
pp. 263-274 ◽  
Author(s):  
BAOLERI LEE ◽  
CHARLOTTE K. SCHJERLING ◽  
NIKOLAI KIRKBY ◽  
NADINE HOFFMANN ◽  
REHANNAH BORUP ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Lung Infection ◽  
Chronic Lung Infection

scholarly journals Role of Toll Interleukin-1 Receptor (IL-1R) 8, a Negative Regulator of IL-1R/Toll-Like Receptor Signaling, in Resistance to Acute Pseudomonas aeruginosa Lung Infection

2011 ◽  
Vol 80 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Tania Véliz Rodriguez ◽  
Federica Moalli ◽  
Nadia Polentarutti ◽  
Moira Paroni ◽  
Eduardo Bonavita ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Interleukin 1 ◽  
Bacterial Load ◽  
Lung Infection ◽  
Negative Regulator ◽  
Current Evidence ◽  
Toll Like Receptor ◽  
Content Type ◽  
Deficient Mice

ABSTRACTToll interleukin-1 receptor (IL-1R) 8 (TIR8), also known as single Ig IL-1 receptor (IL-R)-related molecule, or SIGIRR, is a member of the IL-1R-like family, primarily expressed by epithelial cells. Current evidence suggests that TIR8 plays a nonredundant role as a negative regulatorin vivounder different inflammatory conditions that are dependent on IL-R and Toll-like receptor (TLR) activation. In the present study, we examined the role of TIR8 in innate resistance to acute lung infections caused byPseudomonas aeruginosa, a Gram-negative pathogen responsible for life-threatening infections in immunocompromised individuals and cystic fibrosis patients. We show that Tir8 deficiency in mice was associated with increased susceptibility to acuteP. aeruginosainfection, in terms of mortality and bacterial load, and to exacerbated local and systemic production of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], IL-1β, and IL-6) and chemokines (CXCL1, CXCL2, and CCL2). It has been reported that host defense againstP. aeruginosaacute lung infection can be improved by blocking IL-1 since exaggerated IL-1β production may be harmful for the host in this infection. In agreement with these data, IL-1RI deficiency rescues the phenotype observed in Tir8-deficient mice: in Tir8−/−IL-1RI−/−double knockout mice we observed higher survival rates, enhanced bacterial clearance, and reduced levels of local and systemic cytokine and chemokine levels than in Tir8-deficient mice. These results suggest that TIR8 has a nonredundant effect in modulating the inflammation caused byP. aeruginosa, in particular, by negatively regulating IL-1RI signaling, which plays a major role in the pathogenesis of this infectious disease.

scholarly journals Anthranilate Acts as a Signal to Modulate Biofilm Formation, Virulence, and Antibiotic Tolerance of Pseudomonas aeruginosa and Surrounding Bacteria

2022 ◽  
Author(s):  
Hyeon-Ji Hwang ◽  
Xi-Hui Li ◽  
Soo-Kyoung Kim ◽  
Joon-Hee Lee
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Biofilm Formation ◽  
Chronic Infection ◽  
Antibiotic Tolerance ◽  
Content Type ◽  
Before And After

Pseudomonas aeruginosa is a notorious pathogen with high antibiotic resistance, strong virulence, and ability to cause biofilm-mediated chronic infection. We found that these characteristics change profoundly before and after the time when anthranilate is produced as an “anthranilate peak”.

scholarly journals P678 Definition of a microbial signature as a predictor of post-surgical recurrence in patients with Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S599-S600
Author(s):  
L Oliver ◽  
J Amoedo ◽  
D Julià ◽  
B Camps ◽  
S Ramió-Pujol ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bacterial Load ◽  
High Capacity ◽  
Intestinal Resection ◽  
Preventive Treatment ◽  
Endoscopic Recurrence ◽  
Surgical Recurrence ◽  
Before And After ◽  
One Year

Abstract Background Although there are several effective drugs for the treatment of Crohn’s disease (CD), almost 80% of patients will end up needing a surgical resection throughout their lives. This procedure is not always curative, as the disease often reappears in the intestine. Endoscopic recurrence occurs in 65%-90% of patients after one year from surgery. The aetiology of the recurrence is unknown; however, several studies have shown how the resident microbiota is modified after surgery. The aim of this study is to evaluate samples from patients with CD before and after an intestinal resection to determine if at baseline there are differences in the abundance of different microbial markers, which could be capable of predicting endoscopic recurrences. Methods In this observational study, a stool sample was obtained from 20 patients with CD before undergoing surgery, recruited at Hospital Universitari Dr. Josep Trueta, Hospital Universitari of Bellvitge, and the Hospital Universitari Germans Trias i Pujol. From each sample, DNA was purified and the relative abundance of the following microbial markers was quantified using qPCR: F. prausnitzii (Fpra) and its phylogroups (PHG-I and PHG-II), E. coli (Eco ), A. muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac), M. smithii (Msm), and total bacterial load (Eub). Results Individually, none of the biomarkers demonstrated the ability to differentiate patients who will develop post-surgical recurrence from those who will not. In contrast, the combination of 4 microbial markers (Eco, PHGI, Bac, and Eub) showed a high capacity of discrimination between the 2 groups. The algorithm that incorporates these three markers shows a sensitivity and specificity of 100% and 90.91%, respectively, and a positive and negative predictive value of 90.00% and 100%, respectively. Conclusion A microbial signature to determine patients who will have post-surgical recurrence has been identified. This tool can be very useful in daily clinical practice allowing to schedule a personalized therapy, enabling preventive treatment only in that subgroup of patients who really require it. A broader prospective study will be needed to validate these results.

scholarly journals Adipose-Derived Mesenchymal Stem Cells Ameliorating Pseudomonas aeruginosa–induced Acute Lung Infection via Inhibition of NLRC4 Inflammasome

2021 ◽  
Vol 10 ◽  
Author(s):  
Lu-lu Li ◽  
Ying-gang Zhu ◽  
Xin-ming Jia ◽  
Dong Liu ◽  
Jie-ming Qu
Keyword(s):  
Stem Cells ◽  
Pseudomonas Aeruginosa ◽  
Mesenchymal Stem Cells ◽  
Lung Tissue ◽  
Pulmonary Infection ◽  
Bacterial Load ◽  
Lung Infection ◽  
Inflammasome Activation ◽  
Macrophage Phagocytosis

BackgroundPseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear.ObjectiveThe purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA.MethodsThe therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an in vitro model stimulated by PA and co-cultured with ASCs.Results1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. PA infection mainly activated Nod-like receptor containing a caspase activating and recruitment domain 4 (NLRC4) inflammasome in the lung of mice. ASCs attenuated acute lung infection in mice by inhibiting NLRC4 inflammasome activation. 3. NLRC4−/− mice showed a significant improvement in survival rate and lung bacterial load after PA infection. 4. ASCs mainly increased expression and secretion of STC‐1 in response to PA‐stimulated NLRC4 inflammasome activation.ConclusionsPA infection attenuated macrophage phagocytosis through activation of NLRC4 inflammasome in macrophages, which eventually led to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.

scholarly journals Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

2004 ◽  
Vol 48 (6) ◽  
pp. 2251-2259 ◽  
Author(s):  
Towako Nagata ◽  
Hiroshi Mukae ◽  
Junichi Kadota ◽  
Tomayoshi Hayashi ◽  
Takeshi Fujii ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Murine Model ◽  
Biofilm Formation ◽  
Term Therapy ◽  
Diffuse Panbronchiolitis ◽  
Chronic Respiratory Infection ◽  
Model Treatment ◽  
Long Term Therapy

ABSTRACT Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation.

scholarly journals Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Laura C. McCaughey ◽  
Neil. D. Ritchie ◽  
Gillian R. Douce ◽  
Thomas J. Evans ◽  
Daniel Walker
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Murine Model ◽  
Lung Infection ◽  
Specific Protein ◽  
Species Specific

scholarly journals Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

2013 ◽  
Vol 57 (11) ◽  
pp. 5527-5535 ◽  
Author(s):  
Xavier Mulet ◽  
Gabriel Cabot ◽  
Alain A. Ocampo-Sosa ◽  
M. Angeles Domínguez ◽  
Laura Zamorano ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Multicenter Study ◽  
Biological Markers ◽  
Biofilm Formation ◽  
Specific Treatment ◽  
Spontaneous Mutant ◽  
Biological Parameters ◽  
Content Type

ABSTRACTA limited number ofPseudomonas aeruginosagenotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study ofP. aeruginosabloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n= 6], ST-111 [n= 7], and ST-235 [n= 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and thein vitrocompetition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies.

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