scholarly journals NtrBC Selectively Regulates Host-Pathogen Interactions, Virulence, and Ciprofloxacin Susceptibility of Pseudomonas aeruginosa

2021 ◽  
Vol 11 ◽  
Author(s):  
Morgan A. Alford ◽  
Beverlie Baquir ◽  
Andy An ◽  
Ka-Yee G. Choi ◽  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Transient State ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Upper Respiratory Tract ◽  
Intrinsic Resistance ◽  
Swarming Motility ◽  
Adaptive Resistance ◽  
Host Interactions

Pseudomonas aeruginosa is a metabolically versatile opportunistic pathogen capable of infecting distinct niches of the human body, including skin wounds and the lungs of cystic fibrosis patients. Eradication of P. aeruginosa infection is becoming increasingly difficult due to the numerous resistance mechanisms it employs. Adaptive resistance is characterized by a transient state of decreased susceptibility to antibiotic therapy that is distinct from acquired or intrinsic resistance, can be triggered by various environmental stimuli and reverted by removal of the stimulus. Further, adaptive resistance is intrinsically linked to lifestyles such as swarming motility and biofilm formation, both of which are important in infections and lead to multi-drug adaptive resistance. Here, we demonstrated that NtrBC, the master of nitrogen control, had a selective role in host colonization and a substantial role in determining intrinsic resistance to ciprofloxacin. P. aeruginosa mutant strains (ΔntrB, ΔntrC and ΔntrBC) colonized the skin but not the respiratory tract of mice as well as WT and, unlike WT, could be reduced or eradicated from the skin by ciprofloxacin. We hypothesized that nutrient availability contributed to these phenomena and found that susceptibility to ciprofloxacin was impacted by nitrogen source in laboratory media. P. aeruginosa ΔntrB, ΔntrC and ΔntrBC also exhibited distinct host interactions, including modestly increased cytotoxicity toward human bronchial epithelial cells, reduced virulence factor production and 10-fold increased uptake by macrophages. These data might explain why NtrBC mutants were less adept at colonizing the upper respiratory tract of mice. Thus, NtrBC represents a link between nitrogen metabolism, adaptation and virulence of the pathogen P. aeruginosa, and could represent a target for eradication of recalcitrant infections in situ.

scholarly journals Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient

2020 ◽  
Vol 9 (26) ◽  
Author(s):  
Andrea Sass ◽  
Tom Coenye
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Cystic Fibrosis Patient ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Opportunistic Pathogen ◽  
Content Type ◽  
Airway Infections ◽  
Early Isolate

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

scholarly journals Pseudomonas aeruginosa Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump

2020 ◽  
Author(s):  
Zheng Fan ◽  
Xiaolei Pan ◽  
Dan Wang ◽  
Ronghao Chen ◽  
Tongtong Fu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Opportunistic Pathogen ◽  
Aminoglycoside Antibiotics ◽  
Polynucleotide Phosphorylase ◽  
Multidrug Efflux ◽  
Intrinsic Resistance ◽  
Multidrug Efflux Pump ◽  
Fluoroquinolone Antibiotics

Pseudomonas aeruginosa is an opportunistic pathogen that shows high intrinsic resistance to a variety of antibiotics. The MexX-MexY-OprM efflux pump plays an important role in the bacterial resistance to aminoglycoside antibiotics. Polynucleotide phosphorylase (PNPase) is a highly conserved exonuclease that plays important roles in RNA processing and bacterial response to environmental stresses. Previously, we demonstrated that PNPase controls the tolerance to fluoroquinolone antibiotics by influencing the production of pyocin in P. aeruginosa. In this study, we found that mutation of the PNPase coding gene (pnp) in P. aeruginosa increases the bacterial tolerance to aminoglycoside antibiotics. We further demonstrate that upregulation of the mexXY genes is responsible for the increased tolerance in the pnp mutant. Furthermore, our experimental results revealed that PNPase controls translation of the armZ mRNA through its 5′ untranslated region (5′-UTR). ArmZ had previously been shown to positively regulate the expression of mexXY. Therefore, our results revealed a novel role of PNPase in the regulation of armZ and subsequently the MexXY efflux pump.

scholarly journals Life in the cystic fibrosis upper respiratory tract influences competitive ability of the opportunistic pathogen Pseudomonas aeruginosa

2018 ◽  
Vol 5 (9) ◽  
pp. 180623 ◽  
Author(s):  
Jeffrey J. Bara ◽  
Zachary Matson ◽  
Susanna K. Remold
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Competitive Ability ◽  
Incubation Temperature ◽  
Interference Competition ◽  
Opportunistic Pathogen ◽  
Shared Environment ◽  
Upper Respiratory Tract ◽  
Environmental Isolates ◽  
Bacteriocin Gene

Understanding characteristic differences between host-associated and free-living opportunistic pathogens can provide insight into the fundamental requirements for success after dispersal to the host environment, and more generally into the ecological and evolutionary processes by which populations respond to simultaneous selection on complex interacting traits. We examined how cystic fibrosis (CF)-associated and environmental isolates of the opportunistic pathogen Pseudomonas aeruginosa differ in the production of an ecologically important class of proteinaceous toxins known as bacteriocins, and how overall competitive ability depends on the production of and resistance to these bacteriocins. We determined bacteriocin gene content in a diverse collection of environmental and CF isolates and measured bacteriocin-mediated inhibition, resistance and the outcome of competition in a shared environment between all possible pairs of these isolates at 25°C and 37°C. Although CF isolates encoded significantly more bacteriocin genes, our phenotypic assays suggest that they have diminished bacteriocin-mediated killing and resistance capabilities relative to environmental isolates, regardless of incubation temperature. Notably, however, although bacteriocin killing and resistance profiles significantly predicted head-to-head competitive outcomes, CF and environmental isolates did not differ significantly in their competitive ability. This suggests that the contribution of bacteriocins to competitive ability involves selection on other traits that may be pleiotropically linked to interference competition mediated by bacteriocins.

scholarly journals Genotyping of Different Pseudomonas Aeruginosa Morphotypes Arising from the Lower Respiratory Tract of a Patient Taken to an Intensive Care Unit

2008 ◽  
Vol 21 (4) ◽  
pp. 941-947 ◽  
Author(s):  
L. Putignani ◽  
R. Sessa ◽  
A. Petrucca ◽  
C. Manfredini ◽  
L. Coltella ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Intensive Care ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Opportunistic Pathogen ◽  
Growth Media ◽  
Environmental Bacterium ◽  
Genotypic Analysis

Pseudomonas aeruginosa is an opportunistic pathogen and an ubiquitous environmental bacterium. Fifty-seven days after hospitalization, we isolated three distinct P. aeruginosa morphotypes (smooth, rough and mucoid) from the lower respiratory tract of a patient admitted to a Cardiology Intensive Care Unit (ICU). Moreover, a group of nine colony variants, arising from the three P. aeruginosa isolates growing in laboratory growth media, were also isolated. The resulting 12 isolates were characterised for antibiotic resistance profile and subjected to genotypic analysis by fluorescent-Amplified Fragment Length Polymorphism (f-AFLP) and automated repetitive extragenic palindromic-PCR (rep-PCR) fingerprinting. The three smooth, rough and mucoid morphotypes presented different antibiotic resistance profiles and genotyping analysis showed that they belonged to distinct clones, indicating that at day 57 after the admission the patient was simultaneously colonized by three distinct P. aeruginosa isolates. On the other hand, the nine colony variants presented heterogeneous antibiotic resistance profiles and clustered together with the three parental isolates. The understanding of the link between genotype plasticity and antibiotic resistance may contribute to improving our knowledge of this life-threatening pathogen.

scholarly journals PQS Produced by the Pseudomonas aeruginosa Stress Response Repels Swarms Away from Bacteriophage and Antibiotics

2019 ◽  
Vol 201 (23) ◽  
Author(s):  
Jean-Louis Bru ◽  
Brandon Rawson ◽  
Calvin Trinh ◽  
Katrine Whiteson ◽  
Nina Molin Høyland-Kroghsbo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Stress Response ◽  
Antibiotic Treatment ◽  
Bacterial Pathogen ◽  
Warning Signal ◽  
Opportunistic Pathogen ◽  
Evolutionary Strategy ◽  
Swarming Motility ◽  
Content Type ◽  
Bacteriophage Infection

ABSTRACT We investigate the effect of bacteriophage infection and antibiotic treatment on the coordination of swarming, a collective form of flagellum- and pilus-mediated motility in bacteria. We show that phage infection of the opportunistic bacterial pathogen Pseudomonas aeruginosa abolishes swarming motility in the infected subpopulation and induces the release of the Pseudomonas quinolone signaling molecule PQS, which repulses uninfected subpopulations from approaching the infected area. These mechanisms have the overall effect of limiting the infection to a subpopulation, which promotes the survival of the overall population. Antibiotic treatment of P. aeruginosa elicits the same response, abolishing swarming motility and repulsing approaching swarms away from the antibiotic-treated area through a PQS-dependent mechanism. Swarms are entirely repelled from the zone of antibiotic-treated P. aeruginosa, consistent with a form of antibiotic evasion, and are not repelled by antibiotics alone. PQS has multiple functions, including serving as a quorum-sensing molecule, activating an oxidative stress response, and regulating the release of virulence and host-modifying factors. We show that PQS serves additionally as a stress warning signal that causes the greater population to physically avoid cell stress. The stress response at the collective level observed here in P. aeruginosa is consistent with a mechanism that promotes the survival of bacterial populations. IMPORTANCE We uncover a phage- and antibiotic-induced stress response in the clinically important opportunistic pathogen Pseudomonas aeruginosa. Phage-infected P. aeruginosa subpopulations are isolated from uninfected subpopulations by the production of a stress-induced signal. Activation of the stress response by antibiotics causes P. aeruginosa to physically be repelled from the area containing antibiotics altogether, consistent with a mechanism of antibiotic evasion. The stress response observed here could increase P. aeruginosa resilience against antibiotic treatment and phage therapy in health care settings, as well as provide a simple evolutionary strategy to avoid areas containing stress.

scholarly journals Inference of the phenotypic resistance profile of Pseudomonas aeruginosa through an interpretative reading of the antibiogram in a pediatric hospital. 2006-2014.

2016 ◽  
Vol 64 (3) ◽  
pp. 409
Author(s):  
Juan Jailer Arango ◽  
Aura Lucia Leal ◽  
Maria Del Pilar Montilla ◽  
German Camacho Moreno
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Capacity ◽  
Pediatric Intensive Care ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Resistance Phenotype ◽  
Phenotypic Resistance ◽  
Male Subjects

Introduction: Pseudomonas aeruginosa behaves as an opportunistic pathogen involved in hospital infections, with high capacity to generate resistance to antibiotic treatment. The interpretative reading of the antibiogram makes possible inferring these resistance mechanisms and establishing appropriate antibiotic treatment.Objective: The interpretative reading of the antibiogram seeks to infer the resistance phenotype of P. aeruginosa at Fundación Hospital de la Misericordia (HOMI, by its acronym in Spanish) between 2006 and 2014.Materials and methods: Descriptive cross-sectional study where a search of positive antibiogram reports for P. aeruginosa was performed. The resistance phenotype was deduced based on the interpretative reading of the antibiogram.Results: A sample of 463 positive antibiograms for P. aeruginosa was obtained; these samples were taken from children aged 0 to 17, showing a higher prevalence among infants and toddlers. The antibiograms mainly came from male subjects (62.2%). The most frequent hospitalization services were: PICU —pediatric intensive care unit— (30.2%) and general hospitalization (27.3%). The most common sources of isolation were: blood (24.4%) and urine (23.8%). 11 phenotypes were characterized, being the most common: natural phenotype (63.2%), loss of porin OprD (5.7%) and partial and full AmpC derepression (8.4% and 8.2%, respectively).Conclusion: Isolation of P. aeruginosa at HOMI predominantly shows a natural phenotype. The interpretative reading of the antibiogram allowed inferring 11 phenotypes.

Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation

Microbiology ◽  
2005 ◽  
Vol 151 (5) ◽  
pp. 1313-1323 ◽  
Author(s):  
Denis Tielker ◽  
Stephanie Hacker ◽  
Remy Loris ◽  
Martin Strathmann ◽  
Jost Wingender ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Biofilm Formation ◽  
Membrane Fraction ◽  
Opportunistic Pathogen ◽  
Cell Fractionation ◽  
Intrinsic Resistance ◽  
Outer Membrane Fraction ◽  
Airway Mucosa ◽  
Tract Infections

Pseudomonas aeruginosa is an opportunistic pathogen which causes a variety of diseases, including respiratory tract infections in patients suffering from cystic fibrosis. Therapeutic treatment of P. aeruginosa infections is still very difficult because the bacteria exhibit high intrinsic resistance against a variety of different antibiotics and, in addition, form stable biofilms, e.g. in the human lung. Several virulence factors are produced by P. aeruginosa, among them the two lectins LecA and LecB, which exert different cytotoxic effects on respiratory epithelial cells and presumably facilitate bacterial adhesion to the airway mucosa. Here, the physiology has been studied of the lectin LecB, which binds specifically to l-fucose. A LecB-deficient P. aeruginosa mutant was shown to be impaired in biofilm formation when compared with the wild-type strain, suggesting an important role for LecB in this process. This result prompted an investigation of the subcellular localization of LecB by cell fractionation and subsequent immunoblotting. The results show that LecB is abundantly present in the bacterial outer-membrane fraction. It is further demonstrated that LecB could be released specifically by treatment of the outer-membrane fraction with p-nitrophenyl α-l-fucose, whereas treatment with d-galactose had no effect. In contrast, a LecB protein carrying the mutation D104A, which results in a defective sugar-binding site, was no longer detectable in the membrane fraction, suggesting that LecB binds to specific carbohydrate ligands located at the bacterial cell surface. Staining of biofilm cells using fluorescently labelled LecB confirmed the presence of these ligands.

scholarly journals Complex Ciprofloxacin Resistome Revealed by Screening a Pseudomonas aeruginosa Mutant Library for Altered Susceptibility

2008 ◽  
Vol 52 (12) ◽  
pp. 4486-4491 ◽  
Author(s):  
Elena B. M. Breidenstein ◽  
Bhavjinder K. Khaira ◽  
Irith Wiegand ◽  
Joerg Overhage ◽  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mutant Library ◽  
Intrinsic Resistance ◽  
Adaptive Resistance ◽  
Broth Dilution

ABSTRACT Pseudomonas aeruginosa offers substantial therapeutic challenges due to its high intrinsic resistance to many antibiotics and its propensity to develop mutational and/or adaptive resistance. The PA14 comprehensive mutant library was screened for mutants exhibiting either two- to eightfold increased susceptibilities (revealing genes involved in intrinsic resistance) or decreased susceptibilities (mutational resistance) to the fluoroquinolone ciprofloxacin. Thirty-five and 79 mutants with increased and decreased susceptibilities, respectively, were identified, as confirmed by broth dilution.

scholarly journals Stomatococcus mucilaginosus meningitis in a healthy 2-month-old child

2008 ◽  
Vol 57 (3) ◽  
pp. 382-383 ◽  
Author(s):  
Meher Rizvi ◽  
Nazish Fatima ◽  
Indu Shukla ◽  
Kamran Afzal
Keyword(s):  
Respiratory Tract ◽  
Healthy Child ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Immunocompromised Patients ◽  
Upper Respiratory Tract ◽  
Gram Positive ◽  
Normal Human ◽  
Upper Respiratory

Stomatococcus mucilaginosus is a Gram-positive, catalase-variable organism considered part of the normal human oral and upper respiratory tract flora. Although traditionally believed to be an organism of low virulence, Stomatococcus mucilaginosus has been reported to be an opportunistic pathogen in immunocompromised patients. We describe what we believe is the first reported case of Stomatococcus mucilaginosus meningitis in a healthy child. The isolate was multidrug-resistant, susceptible only to vancomycin. The patient was treated successfully with vancomycin after initial trials with amikacin and cefotaxime.

scholarly journals The Prevalence of Metallo-β-Lactamases and Efflux-Mediated Mechanisms in Carbapenem Nonsusceptible Nosocomial Pseudomonas aeruginosa Isolated in Moscow in 2012–2015

2015 ◽  
Vol 70 (6) ◽  
pp. 679-683
Author(s):  
Anna Valer'evna Lazareva ◽  
Ol'ga Andreevna Kryzhanovskaya ◽  
Yuliya Aleksandrovna Bocharova ◽  
Igor' Viktorovich Chebotar' ◽  
Nikolay Andreevich Mayanskiy
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Carbapenem Resistance ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Active Efflux ◽  
Minimal Inhibitory Concentrations ◽  
Highly Active ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Carbonyl Cyanide

Background. Pseudomonas aeruginosa, the major nosocomial opportunistic pathogen, is an important cause of infectious morbidity and mortality among immunocompromised patients.Objective. To establish the role of metallo-β-lactamases (MBL) and efflux-mediated mechanisms in conferring carbapenem resistance in nosocomial isolates of P. aeruginosa.Methods. We analyzed carbapenem nonsusceptible nosocomial P. aeruginosa isolates obtained from pediatric and adult patients at three hospitals in Moscow in 2012–2015. Carbapenem susceptibility was assessed using the E-test. In addition, minimal inhibitory concentrations (MICs) of meropenem were tested by the broth microdilution method. The presence of MBL was determined using the EDTA-mediated suppression test. Efflux-dependent resistance was measured using an assay based on MIC modification by an ionophore carbonyl cyanide 3-chlorophenyl hydrazine (CCCP).Results. A total of 54 carbapenem nonsusceptible P. aeruginosa isolates was examined. The presence of an MBL was detected in 37 (69%) isolates, 29 (54%) isolates had efflux-mediated resistance. In 10 (19%) isolates neither MBL nor efflux activity was found. Five out of 6 isolates (83%) with highly active efflux were MBL-positive. Among isolates with low efflux activity, 74% (17/23) possessed MBL, whereas in isolates with no efflux the rate of MBL-positivity was 60% (15/25).Conclusion. The prevalence of MBL- and efflux-mediated carbapenem resistance in nosocomial P. aeruginosa is high. Moreover, our results reveal that several resistance mechanisms may combine at the isolate level. These data may contribute to the development of novel strategies in combating carbapenem resistance.

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