scholarly journals Antimicrobial Resistance and Type III Secretion System Virulotypes of Pseudomonas aeruginosa Isolates from Dogs and Cats in Primary Veterinary Hospitals in Japan: Identification of the International High-Risk Clone Sequence Type 235

2021 ◽  
Author(s):  
Wataru Hayashi ◽  
Katsutoshi Izumi ◽  
Satoshi Yoshida ◽  
Shino Takizawa ◽  
Kanae Sakaguchi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Virulence Determinants ◽  
Content Type ◽  
Clone Sequence ◽  
Life Threatening ◽  
Health Care Associated Infections ◽  
Opportunistic Human Pathogen

Pseudomonas aeruginosa is an environmentally ubiquitous and important opportunistic human pathogen responsible for life-threatening health care-associated infections. Because of its extensive repertoire of virulence determinants and intrinsic and acquired resistance mechanisms, the organism could be one of the most clinically and epidemiologically important causes of morbidity and mortality.

scholarly journals Development and Application of a Core Genome Multilocus Sequence Typing Scheme for the Health Care-Associated Pathogen Pseudomonas aeruginosa

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Richard A. Stanton ◽  
Gillian McAllister ◽  
Jonathan B. Daniels ◽  
Erin Breaker ◽  
Nicholas Vlachos ◽  
...  
Keyword(s):  
Health Care ◽  
Pseudomonas Aeruginosa ◽  
Multilocus Sequence Typing ◽  
Core Genome ◽  
Health Care Environment ◽  
Content Type ◽  
Health Care Associated Infections ◽  
Opportunistic Human Pathogen ◽  
The Stability ◽  
Core Genes

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen that frequently causes health care-associated infections (HAIs). Due to its metabolic diversity and ability to form biofilms, this Gram-negative nonfermenting bacterium can persist in the health care environment, which can lead to prolonged HAI outbreaks. We describe the creation of a core genome multilocus sequence typing (cgMLST) scheme to provide a stable platform for the rapid comparison of P. aeruginosa isolates using whole-genome sequencing (WGS) data. We used a diverse set of 58 complete P. aeruginosa genomes to curate a set of 4,440 core genes found in each isolate, representing ∼64% of the average genome size. We then expanded the alleles for each gene using 1,991 contig-level genome sequences. The scheme was used to analyze genomes from four historical HAI outbreaks to compare the phylogenies generated using cgMLST to those of other means (traditional MLST, pulsed-field gel electrophoresis [PFGE], and single-nucleotide variant [SNV] analysis). The cgMLST scheme provides sufficient resolution for analyzing individual outbreaks, as well as the stability for comparisons across a variety of isolates encountered in surveillance studies, making it a valuable tool for the rapid analysis of P. aeruginosa genomes.

scholarly journals Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Yanyan Hu ◽  
Yan Qing ◽  
Jiawei Chen ◽  
Congcong Liu ◽  
Jiayue Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Gastrointestinal Tract ◽  
Resistance Genes ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Human Gastrointestinal Tract ◽  
Content Type ◽  
Carbapenem Resistant

Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes.

scholarly journals Draft Genome Sequences of Two Pseudomonas aeruginosa Multidrug-Resistant Clinical Isolates, PAL0.1 and PAL1.1

2018 ◽  
Vol 7 (17) ◽  
Author(s):  
Teddy Grandjean ◽  
Rémi Le Guern ◽  
Claire Duployez ◽  
Karine Faure ◽  
Eric Kipnis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Draft Genome ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Blood Cultures ◽  
Ventilator Associated Pneumonia ◽  
Genome Sequences ◽  
Content Type ◽  
Resistant Strains

Pseudomonas aeruginosa infections are challenging due to intrinsic and acquired resistance mechanisms. We report here the draft genome sequences of two multidrug-resistant strains—PAL0.1, isolated from the airways of an intensive care unit (ICU) patient with ventilator-associated pneumonia, and PAL1.1, isolated from blood cultures of an ICU patient with sepsis.

scholarly journals Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

scholarly journals Serratia marcescens ShlA Pore-Forming Toxin Is Responsible for Early Induction of Autophagy in Host Cells and Is Transcriptionally Regulated by RcsB

2014 ◽  
Vol 82 (9) ◽  
pp. 3542-3554 ◽  
Author(s):  
Gisela Di Venanzio ◽  
Tatiana M. Stepanenko ◽  
Eleonora García Véscovi
Keyword(s):  
Serratia Marcescens ◽  
Promoter Region ◽  
Regulatory Mechanism ◽  
Host Cells ◽  
Binding Motif ◽  
Content Type ◽  
Life Threatening ◽  
Opportunistic Human Pathogen ◽  
Flagellar Biogenesis ◽  
Fine Tune

ABSTRACTSerratia marcescensis a Gram-negative bacterium that thrives in a wide variety of ambient niches and interacts with an ample range of hosts. As an opportunistic human pathogen, it has increased its clinical incidence in recent years, being responsible for life-threatening nosocomial infections.S. marcescensproduces numerous exoproteins with toxic effects, including the ShlA pore-forming toxin, which has been catalogued as its most potent cytotoxin. However, the regulatory mechanisms that govern ShlA expression, as well as its action toward the host, have remained unclear. We have shown thatS. marcescenselicits an autophagic response in host nonphagocytic cells. In this work, we determine that the expression of ShlA is responsible for the autophagic response that is promoted prior to bacterial internalization in epithelial cells. We show that a strain unable to express ShlA is no longer able to induce this autophagic mechanism, while heterologous expression of ShlA/ShlB suffices to confer on noninvasiveEscherichia colithe capacity to trigger autophagy. We also demonstrate thatshlBAharbors a binding motif for the RcsB regulator in its promoter region. RcsB-dependent control ofshlBAconstitutes a feed-forward regulatory mechanism that allows interplay with flagellar-biogenesis regulation. At the top of the circuit, activated RcsB downregulates expression of flagella by binding to theflhDCpromoter region, preventing FliA-activated transcription ofshlBA. Simultaneously, RcsB interaction within theshlBApromoter represses ShlA expression. This circuit offers multiple access points to fine-tune ShlA production. These findings also strengthen the case for an RcsB role in orchestrating the expression ofSerratiavirulence factors.

A Critical Evaluation of Newer β-Lactam Antibiotics for Treatment of Pseudomonas aeruginosa Infections

2020 ◽  
pp. 106002802097400
Author(s):  
Kathleen C. Blomquist ◽  
David E. Nix
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Data ◽  
Therapeutic Potential ◽  
Data Extraction ◽  
Relevant Literature ◽  
Acquired Resistance ◽  
Critical Evaluation ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Study Selection

Objective: This article critically evaluates common Pseudomonas aeruginosa resistance mechanisms and the properties newer β-lactam antimicrobials possess to evade these mechanisms. Data Sources: An extensive PubMed, Google Scholar, and ClinicalTrials.gov search was conducted (January 1995 to July 2020) to identify relevant literature on epidemiology, resistance mechanisms, antipseudomonal agents, newer β-lactam agents, and clinical data available pertaining to P aeruginosa. Study Selection and Data Extraction: Relevant published articles and package inserts were reviewed for inclusion. Data Synthesis: Therapeutic options to treat P aeruginosa infections are limited because of its intrinsic and acquired resistance mechanisms. The goal was to identify advances with newer β-lactams and characterize improvements in therapeutic potential for P aeruginosa infections. Relevance to Patient Care and Clinical Practice: Multidrug-resistant (MDR) P aeruginosa isolates are increasingly encountered from a variety of infections. This review highlights potential activity gains of newer β-lactam antibacterial drugs and the current clinical data to support their use. Pharmacists will be asked to recommend or evaluate the use of these agents and need to be aware of information specific to P aeruginosa, which differs from experience derived from Enterobacterales infections. Conclusions: Newer agents, including ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol, are useful for the treatment of MDR P aeruginosa infections. These agents offer improved efficacy and less toxicity compared with aminoglycosides and polymyxins and can be used for pathogens that are resistant to first-line antipseudomonal β-lactams. Selection of one agent over another should consider availability, turnaround of susceptibility testing, and product cost. Efficacy data specific for pseudomonal infections are limited, and there are no direct comparisons between the newer agents.

scholarly journals Derivatives of Plant Phenolic Compound Affect the Type III Secretion System of Pseudomonas aeruginosa via a GacS-GacA Two-Component Signal Transduction System

2011 ◽  
Vol 56 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Akihiro Yamazaki ◽  
Jin Li ◽  
Quan Zeng ◽  
Devanshi Khokhani ◽  
William C. Hutchins ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Virulence Factors ◽  
Type Iii Secretion ◽  
Small Rnas ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Human Pathogen ◽  
Content Type ◽  
Type Iii

ABSTRACTAntibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability.Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors by which it secretes and translocates T3 effector proteins into human host cells. The fact that this human pathogen also is able to infect several plant species led us to screen a library of phenolic compounds involved in plant defense signaling and their derivatives for novel T3 inhibitors. Promoter activity screening ofexoS, which encodes a T3-secreted toxin, identified two T3 inhibitors and two T3 inducers ofP. aeruginosaPAO1. These compounds alterexoStranscription by affecting the expression levels of the regulatory small RNAs RsmY and RsmZ. These two small RNAs are known to control the activity of carbon storage regulator RsmA, which is responsible for the regulation of the key T3SS regulator ExsA. As RsmY and RsmZ are the only targets directly regulated by GacA, our results suggest that these phenolic compounds affect the expression ofexoSthrough the GacSA-RsmYZ-RsmA-ExsA regulatory pathway.

scholarly journals Inactivation of the Pseudomonas -Derived Cephalosporinase-3 (PDC-3) by Relebactam

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Melissa D. Barnes ◽  
Christopher R. Bethel ◽  
Jim Alsop ◽  
Scott A. Becka ◽  
Joseph D. Rutter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Life Threatening ◽  
Lactamase Inhibitor

ABSTRACT Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas -derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa . In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a k 2 / K of 41,400 M −1 s −1 and a k off of 0.00095 s −1 . Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa .

scholarly journals cAMP and Vfr Control Exolysin Expression and Cytotoxicity of Pseudomonas aeruginosa Taxonomic Outliers

2018 ◽  
Vol 200 (12) ◽  
Author(s):  
Alice Berry ◽  
Kook Han ◽  
Julian Trouillon ◽  
Mylène Robert-Genthon ◽  
Michel Ragno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Transcriptional Activation ◽  
Opportunistic Pathogen ◽  
Secretion System ◽  
Intracellular Camp ◽  
Virulence Determinants ◽  
Cell Infection ◽  
Content Type

ABSTRACT The two-partner secretion system ExlBA, expressed by strains of Pseudomonas aeruginosa belonging to the PA7 group, induces hemorrhage in lungs due to disruption of host cellular membranes. Here we demonstrate that the exlBA genes are controlled by a pathway consisting of cAMP and the virulence factor regulator (Vfr). Upon interaction with cAMP, Vfr binds directly to the exlBA promoter with high affinity (equilibrium binding constant [ K eq ] of ≈2.5 nM). The exlB and exlA expression was diminished in the Vfr-negative mutant and upregulated with increased intracellular cAMP levels. The Vfr binding sequence in the exlBA promoter was mutated in situ , resulting in reduced cytotoxicity of the mutant, showing that Vfr is required for the exlBA expression during intoxication of epithelial cells. Vfr also regulates function of type 4 pili previously shown to facilitate ExlA activity on epithelial cells, which indicates that the cAMP/Vfr pathway coordinates these two factors needed for full cytotoxicity. As in most P. aeruginosa strains, the adenylate cyclase CyaB is the main provider of cAMP for Vfr regulation during both in vitro growth and eukaryotic cell infection. We discovered that the absence of functional Vfr in the reference strain PA7 is caused by a frameshift in the gene and accounts for its reduced cytotoxicity, revealing the conservation of ExlBA control by the CyaB-cAMP/Vfr pathway in P. aeruginosa taxonomic outliers. IMPORTANCE The human opportunistic pathogen Pseudomonas aeruginosa provokes severe acute and chronic human infections associated with defined sets of virulence factors. The main virulence determinant of P. aeruginosa taxonomic outliers is exolysin, a membrane-disrupting pore-forming toxin belonging to the two-partner secretion system ExlBA. In this work, we demonstrate that the conserved CyaB-cAMP/Vfr pathway controls cytotoxicity of outlier clinical strains through direct transcriptional activation of the exlBA operon. Therefore, despite the fact that the type III secretion system and exolysin are mutually exclusive in classical and outlier strains, respectively, these two major virulence determinants share similarities in their mechanisms of regulation.

scholarly journals Contextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Stephen K. Dolan ◽  
Michael Kohlstedt ◽  
Stephen Trigg ◽  
Pedro Vallejo Ramirez ◽  
Clemens F. Kaminski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Metabolic Flux ◽  
Antimicrobial Agents ◽  
Carbon Sources ◽  
Aerobic Denitrification ◽  
Human Pathogen ◽  
Content Type ◽  
Opportunistic Human Pathogen

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized “EDEMP cycle” (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each. IMPORTANCE Pseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer (“fluxomic”) analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed (“fluxed”) through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell’s electron transfer pathways. Having access to this “blueprint” is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.

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