scholarly journals The putative bacterial oxygen sensor Pseudomonas prolyl hydroxylase (PPHD) suppresses antibiotic resistance and pathogenicity in Pseudomonas aeruginosa

2019 ◽  
Vol 295 (5) ◽  
pp. 1195-1201 ◽  
Author(s):  
Bettina Schaible ◽  
Bianca Crifo ◽  
Kirsten Schaffer ◽  
Cormac T. Taylor
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Oxygen Sensor ◽  
Bacterial Pathogen ◽  
Clinical Problem ◽  
Infectious Complications ◽  
Prolyl Hydroxylase ◽  
Oxygen Levels ◽  
Multiple Strains ◽  
Underlying Diseases

Pseudomonas aeruginosa is an extracellular opportunistic bacterial pathogen commonly associated with infectious complications in susceptible individuals, such as those with underlying diseases including HIV/AIDS and cystic fibrosis. Antibiotic resistance in multiple strains of P. aeruginosa is a rapidly developing clinical problem. We have previously demonstrated that the oxygen levels at the site of P. aeruginosa infection can strongly influence virulence and antibiotic resistance in this pathogen, although the oxygen-sensing and -signaling mechanisms underpinning this response have remained unknown. In this study, we investigated the potential role of the putative oxygen sensor Pseudomonas prolyl hydroxylase (PPHD) in the control of virulence and antibiotic resistance in P. aeruginosa. We found that a P. aeruginosa strain lacking PPHD (PAO310) exhibits increased virulence associated with increased bacterial motility. Furthermore, PPHD-deficient P. aeruginosa displayed enhanced antibiotic resistance against tetracycline through increased expression of the xenobiotic transporters mexEF-oprN and MexXY. Of note, the effect of the PPHD knockout on antibiotic resistance was phenocopied in bacteria exposed to atmospheric hypoxia. We conclude that PPHD is a putative bacterial oxygen sensor that may link microenvironmental oxygen levels to virulence and antibiotic resistance in P. aeruginosa.

scholarly journals Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa

2020 ◽  
Vol 2020 (1) ◽  
pp. 148-157 ◽  
Author(s):  
James Gurney ◽  
Léa Pradier ◽  
Joanne S Griffin ◽  
Claire Gougat-Barbera ◽  
Benjamin K Chan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogen ◽  
Antibiotic Sensitivity ◽  
Resistant Bacteria ◽  
Phage Resistance ◽  
Antibiotic Resistant ◽  
Trade Off

Abstract Background and objectives Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance—so called ‘phage steering’. Methodology Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). Results We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. Conclusions and implications Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called ‘steering phages’ kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

scholarly journals Inhibition of Pseudomonas aeruginosa Biofilm Formation with Surface Modified Polymeric Nanoparticles

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 55 ◽  
Author(s):  
Tyler Flockton ◽  
Logan Schnorbus ◽  
Agustin Araujo ◽  
Jill Adams ◽  
Maryjane Hammel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Polymeric Nanoparticles ◽  
Bacterial Pathogen ◽  
Gram Negative ◽  
Treatment Technologies ◽  
New Treatment ◽  
Surface Modified

The gram-negative bacterial pathogen Pseudomonas aeruginosa represents a prominent clinical concern. Due to the observed high levels of antibiotic resistance, copious biofilm formation, and wide array of virulence factors produced by these bacteria, new treatment technologies are required. Here, we present the development of a series of P. aeruginosa LecA-targeted polymeric nanoparticles and demonstrate the anti-adhesion and biofilm inhibitory properties of these constructs.

scholarly journals Competition in Biofilms between Cystic Fibrosis Isolates ofPseudomonas aeruginosaIs Shaped by R-Pyocins

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. e01828-18 ◽  
Author(s):  
Olubukola Oluyombo ◽  
Christopher N. Penfold ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Clinical Problem ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Content Type ◽  
Global Concern ◽  
Antibiofilm Agents ◽  
Major Clinical Problem

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen and the leading cause of morbidity and mortality in cystic fibrosis (CF) patients.P. aeruginosainfections are difficult to treat due to a number of antibiotic resistance mechanisms and the organism’s propensity to form multicellular biofilms. Epidemic strains ofP. aeruginosaoften dominate within the lungs of individual CF patients, but how they achieve this is poorly understood. One way that strains ofP. aeruginosacan compete is by producing chromosomally encoded bacteriocins, called pyocins. Three major classes of pyocin have been identified inP. aeruginosa: soluble pyocins (S types) and tailocins (R and F types). In this study, we investigated the distribution of S- and R-type pyocins in 24 clinical strains isolated from individual CF patients and then focused on understanding their roles in interstrain competition. We found that (i) each strain produced only one R-pyocin type, but the number of S-pyocins varied between strains, (ii) R-pyocins were generally important for strain dominance during competition assays in planktonic cultures and biofilm communities in strains with both disparate R- and S-pyocin subtypes, and (iii) purified R-pyocins demonstrated significant antimicrobial activity against established biofilms. Our work provides support for a role played by R-pyocins in the competition betweenP. aeruginosastrains and helps explain why certain strains and lineages ofP. aeruginosadominate and displace others during CF infection. Furthermore, we demonstrate the potential of exploiting R-pyocins for therapeutic gains in an era when antibiotic resistance is a global concern.IMPORTANCEA major clinical problem caused byPseudomonas aeruginosa, is chronic biofilm infection of the lungs in individuals with cystic fibrosis (CF). EpidemicP. aeruginosastrains dominate and displace others during CF infection, but these intraspecies interactions remain poorly understood. Here we demonstrate that R-pyocins (bacteriocins) are important factors in driving competitive interactions in biofilms betweenP. aeruginosastrains isolated from different CF patients. In addition, we found that these phage-like pyocins are inhibitory against mature biofilms of susceptible strains. This highlights the potential of R-pyocins as antimicrobial and antibiofilm agents at a time when new antimicrobial therapies are desperately needed.

scholarly journals Competition in biofilms between cystic fibrosis isolates ofPseudomonas aeruginosais shaped by R-pyocins

2018 ◽  
Author(s):  
Olubukola Oluyombo ◽  
Christopher N. Penfold ◽  
Stephen P. Diggle
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Species Interactions ◽  
Clinical Problem ◽  
Opportunistic Pathogen ◽  
Resistance Mechanisms ◽  
Global Concern ◽  
Human Infections ◽  
Antibiofilm Agents

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen responsible for a number of different human infections and is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients.P. aeruginosainfections are difficult to treat due to a number of antibiotic resistance mechanisms and the organisms propensity to form multicellular biofilms. Epidemic strains ofP. aeruginosaoften dominate within the lungs of individual CF patients, but how they achieve this is poorly understood. One of the ways strains ofP. aeruginosacan compete, is by producing chromosomally encoded bacteriocins, called pyocins. Three major classes of pyocin have been identified inP. aeruginosa:soluble pyocins (S-types) and tailocins (R- and F-types). In this study, we investigated the distribution of S- and R-type pyocins in 24 clinical strains isolated from individual CF patients and then focused on understanding their roles on inter-strain competition. We found that (i) each strain produced only one R-pyocin type, but the number of S-pyocins varied between strains; (ii) R-pyocins were generally important for strain dominance during competition assays in planktonic cultures and biofilm communities in strains with both disparate R and S pyocin sub-types. (iii) purified R-pyocins demonstrated significant antimicrobial activity against established biofilms. Our work provides support for a key role played by R-pyocins in the competition betweenP. aeruginosastrains, and may help explain why certain strains and lineages ofP. aeruginosadominate and displace others during CF lung infection. Furthermore, we demonstrate the potential of exploiting R-pyocins for therapeutic gains in an era when antibiotic resistance is a global concern.IMPORTANCEA major clinical problem caused byPseudomonas aeruginosa, is chronic biofilm infection of the lungs in individuals with cystic fibrosis (CF). EpidemicP. aeruginosastrains dominate and displace others during CF infection, but these intra-species interactions remain poorly understood. Here we demonstrate that R-pyocins (bacterocins) are important factors in driving competitive interactions in biofilms betweenP. aeruginosastrains isolated from different CF patients. In addition, we found that these phage-like pyocins are inhibitory against mature biofilms of susceptible strains. This highlights the potential of R-pyocins as antimicrobial and antibiofilm agents, at a time when new antimicrobial therapies are desperately needed.

Quintuplex PCR to Detect Antibiotic Resistance Genes in Streptococcus pneumoniae

2016 ◽  
Vol 1 (2) ◽  
pp. 22 ◽  
Author(s):  
Navindra Kumari Palanisamy ◽  
Parasakthi Navaratnam ◽  
Shamala Devi Sekaran
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Antibiotic Resistance Genes ◽  
Pcr Amplification ◽  
Penicillin Resistance ◽  
Penicillin Binding Proteins ◽  
Efflux Mechanism ◽  
Mic Value

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.

Epidemiology and antimicrobial resistance of Acinetobacter

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova
Keyword(s):  
Antibiotic Resistance ◽  
Laboratory Testing ◽  
Immunocompromised Host ◽  
Clinical Problem ◽  
Healthcare Associated Infections ◽  
Opportunistic Bacteria ◽  
Acinetobacter Spp ◽  
Healthcare Associated ◽  
Major Clinical Problem

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.

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