scholarly journals rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiangke Duan ◽  
Yanrong Pan ◽  
Zhao Cai ◽  
Yumei Liu ◽  
Yingdan Zhang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Point Mutations ◽  
Opportunistic Pathogen ◽  
Antimicrobial Treatment ◽  
High Dose ◽  
Sequencing Analysis ◽  
Adverse Conditions ◽  
Diguanylate Cyclases ◽  
Cyclic Treatment

Abstract Background Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance. Results In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants. Conclusion Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.

RpoS Mutation Leads to Prolonged Biofilm Mode of Growth and a Higher Fitness in Pseudomonas Aeruginosa Biofilms

2021 ◽  
Author(s):  
Xiangke Duan ◽  
Yanrong Pan ◽  
Zhao Cai ◽  
Yumei Liu ◽  
Yingdan Zhang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Biofilm Formation ◽  
Point Mutations ◽  
Opportunistic Pathogen ◽  
Antimicrobial Treatment ◽  
Clinical Isolates ◽  
High Dose ◽  
Sequencing Analysis ◽  
Cyclic Treatment

Abstract BackgroundPseudomonas aeruginosa is a notorious opportunistic pathogen causing various biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune responses. ResultsIn this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilm by prolonging the biofilm mode of growth but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS enhanced biofilm formation by prolonging the biofilm mode of growth and elevating the intracellular c-di-GMP level. Mutation in rpoS increased pyocyanin production and virulence in both P. aeruginosa laboratory strains and clinical isolates. ConclusionHere, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.

Pseudomonas aeruginosa in Bronchiectasis

2021 ◽  
Vol 42 (04) ◽  
pp. 587-594
Author(s):  
Laia Fernández-Barat ◽  
Victoria Alcaraz-Serrano ◽  
Rosanel Amaro ◽  
Antoni Torres
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chronic Infection ◽  
Opportunistic Pathogen ◽  
Oxygen Depletion ◽  
Antimicrobial Treatment ◽  
Consensus Definition ◽  
Abiotic Surfaces ◽  
Technological Advances ◽  
Patients At Risk ◽  
Definition Of

Abstract Pseudomonas aeruginosa (PA) in patients with bronchiectasis (BE) is associated with a poor outcome and quality of life, and its presence is considered a marker of disease severity. This opportunistic pathogen is known for its ability to produce biofilms on biotic or abiotic surfaces and to survive environmental stress exerted by antimicrobials, inflammation, and nutrient or oxygen depletion. The presence of PA biofilms has been linked to chronic respiratory infection in cystic fibrosis but not in BE. There is considerable inconsistency in the reported infection/eradication rates of PA and chronic PA. In addition, inadequate antimicrobial treatment may potentiate the progression from intermittent to chronic infection and also the emergence of antibiotic resistance. A better comprehension of the pathophysiology of PA infections and its implications for BE is urgently needed. This can drive improvements in diagnostic accuracy, can move us toward a new consensus definition of chronic infection, can better define the follow-up of patients at risk of PA, and can achieve more successful eradication rates. In addition, the new technological advances regarding molecular diagnostics, -omics, and biomarkers require us to reconsider our traditional concepts.

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 Universal antibiotic tolerance arising from antibiotic-triggered accumulation of redox metabolites

2018 ◽  
Author(s):  
Kui Zhu ◽  
Shang Chen ◽  
Tatyana A. Sysoeva ◽  
Lingchong You
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Opportunistic Pathogen ◽  
Antibiotic Tolerance ◽  
Treatment Protocols ◽  
Collective Behaviors ◽  
Redox Active ◽  
Redox Metabolites ◽  
The Individual ◽  
Sublethal Concentrations

AbstractPseudomonas aeruginosais an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established,P. aeruginosainfections are notoriously difficult to eradicate. This difficulty is in part due to the ability ofP. aeruginosato tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here we describe a new mechanism by whichP. aeruginosatolerates antibiotic treatment by modulating its global cellular metabolism. In particular, treatment ofP. aeruginosawith sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine - pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for bothP. aeruginosaand other Gram-negative and Gram-positive bacteria. We show that PYO promotes energy generation to enhance the activity of efflux pumps, leading to enhanced antibiotic tolerance. This property is shared by other redox-active phenazines produced byP. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.Author SummaryAntibiotic tolerance can facilitate the evolution of resistance, and here we describe a previously unknown mechanism of collective antibiotic tolerance inPseudomonas aeruginosa. In particular,P. aeruginosatreated with sublethal concentrations of antibiotics covering all major classes promotes accumulation of pyocyanin (PYO), an important virulence factor. In turn, PYO confers general tolerance against diverse antibiotics for bothP. aeruginosaand other bacteria. Our discovery is a perfect example of what Nietzsche once said:That which does not kill me makes me stronger.

scholarly journals Antimicrobial resistance and novel mutations detected in the gyrA and parC genes of Pseudomonas aeruginosa strains isolated from companion dogs

2020 ◽  
Author(s):  
Youjin Park ◽  
Jaeyoung Oh ◽  
Sowon Park ◽  
Samuth Sum ◽  
Wonkeun Song ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Point Mutations ◽  
Clinical Signs ◽  
Infected Group ◽  
Fluoroquinolone Resistance ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Novel Mutations ◽  
Healthy Group ◽  
Companion Dogs

Abstract Background: Fluoroquinolone agents, such as enrofloxacin and marbofloxacin, are commonly used for pseudomonal infection in veterinary medicine. However, the rate of resistance to fluoroquinolones is rapidly increasing, according to multiple studies in various countries. Point mutations in the quinolone resistance-determining region (QRDR) are closely related to the increased fluoroquinolone resistance of Pseudomonas aeruginosa. The aim of this study was to investigate current antimicrobial susceptibility and fluoroquinolone resistance in P. aeruginosa strains isolated from dogs. The presence of point mutations in the QRDR was confirmed by gyrA and parC polymerase chain reaction and nucleotide sequencing analysis.Results: A total of 84 nonduplicated P. aeruginosa strains were obtained from 228 healthy dogs (healthy group) and 260 dogs with clinical signs (infected group). Among these isolates, 38 strains from the healthy group were detected in several sample types, whereas 46 strains from the infected group were obtained mostly from dogs’ ears with otitis externa (41/260, 15.8%). All strains were resistant to nalidixic acid, while some were also resistant to enrofloxacin (23/84, 27.4%), marbofloxacin (17/84, 20.2%), levofloxacin (12/84, 14.3%), or ciprofloxacin (11/84, 13.1%). Enrofloxacin resistance was significantly higher in strains from the infected group than in those from the healthy group (p<0.05). Among the 23 fluoroquinolone-resistant strains, 8 and 4 different mutations were detected in the gyrA and parC genes, respectively. Mutations in gyrA were significantly common in the infected group (p<0.05). Hotspots for the gyrA and parC mutations were Thr83 (34.8%, 8/23) and Pro116 (91.3%, 21/23), respectively. Double and triple mutations were also found in 5 of the strains.Conclusion: Novel mutations in the gyrA and parC genes were first found in P. aeruginosa isolated from companion dogs in South Korea. These findings suggest that it is important to encourage prudent use of fluoroquinolone antibiotics in canine pseudomonal infection treatment.

Antibiotic treatment of Pseudomonas aeruginosa biofilms stimulates expression of the magnesium transporter gene mgtE

Microbiology ◽  
2014 ◽  
Vol 160 (1) ◽  
pp. 165-178 ◽  
Author(s):  
Carly V. Redelman ◽  
Shubham Chakravarty ◽  
Gregory G. Anderson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Transporter Protein ◽  
Magnesium Transporter ◽  
High Concentrations ◽  
Serious Disease

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with the capacity to cause serious disease, including chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. These infections are treated with high concentrations of antibiotics. Virulence modulation is an important tool utilized by P. aeruginosa to propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified, including the magnesium transporter protein MgtE. We have recently found that isogenic deletion of mgtE leads to increased cytotoxicity through effects on the type III secretion system. To explore the role of the CF lung environment in MgtE activity, we investigated mgtE transcriptional regulation following antibiotic treatment. Utilizing quantitative real-time-PCR, we have demonstrated an increase in mgtE transcript levels following antibiotic treatment with most of the 12 antibiotics tested. To begin to determine the regulatory network governing mgtE expression, we screened a transposon-mutant library of P. aeruginosa to look for mutants with potentially altered mgtE activity, using cytotoxicity as a readout. In this screen, we observed that AlgR, which regulates production of the biofilm polysaccharide alginate, alters MgtE-mediated cytotoxicity. This cross-talk between MgtE and AlgR suggests that AlgR is involved in linking external inducing signals (e.g. antibiotics) to mgtE transcription and downstream virulence and biofilm activities. Analysing such interactions may lead to a better understanding of how the CF lung environment shapes P. aeruginosa biofilm infections.

The In Vitro Antibiofilm Activity of Water Leaf Extract of Papaya (Carica papaya L.) against Pseudomonas aeruginosa

2017 ◽  
Vol 2 (3) ◽  
pp. 150-163
Author(s):  
Ekajayanti Kining ◽  
Syamsul Falah ◽  
Novik Nurhidayat
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Contact Time ◽  
Cell Attachment ◽  
Water Extract ◽  
Opportunistic Pathogen ◽  
Bacterial Biofilm ◽  
Antibiofilm Activity ◽  
Bacterial Survival ◽  
Optimum Conditions

Pseudomonas aeruginosa is one of opportunistic pathogen forming bacterial biofilm. The biofilm sustains the bacterial survival and infections. This study aimed to assess the activity of water extract of papaya leaves on inhibition of cells attachment, growth and degradation of the biofilm using crystal violet (CV) biofilm assay. Research results showed that water extract of papaya leaves contains alkaloids, tanins, flavonoids, and steroids/terpenoids and showed antibacterial activity and antibiofilm against P. aeruginosa. Addition of extract can inhibit the cell attachment and was able to degrade the biofilm of 40.92% and 48.058% respectively at optimum conditions: extract concentration of 25% (v/v), temperature 37.5 °C and contact time 45 minutes. With a concentration of 25% (v/v), temperature of 50 °C and the contact time of 3 days, extract of papaya leaves can inhibit the growth of biofilms of 39.837% v/v.

scholarly journals An Eschar-like souvenir from a journey to Colombia: Ecthyma gangrenosum as a differential diagnosis of tropical diseases in immunocompromised patients – a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriela M. Wiedemann ◽  
Jochen Schneider ◽  
Mareike Verbeek ◽  
Björn Konukiewitz ◽  
Christoph D. Spinner ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Differential Diagnosis ◽  
Antibiotic Treatment ◽  
Partial Remission ◽  
Combined Treatment ◽  
Lymphocytic Leukemia ◽  
Entire Body ◽  
Tropical Diseases ◽  
Ecthyma Gangrenosum ◽  
Skin Ulcers

Abstract Background Ecthyma gangrenosum (EG) is a cutaneous infectious disease characterized by eschar-like skin ulcers typically caused by Pseudomonas aeruginosa. Here, we report a case of relapsing EG in a patient who had returned from a trip to Colombia, thus establishing EG as an important differential diagnosis of tropical diseases, and demonstrating that even long-term antibiotic treatment can result in only partial remission of EG. Case presentation A 77-year-old man with underlying chronic lymphocytic leukemia (CLL) on ibrutinib treatment was admitted because of a superinfected mosquito bite on the left ear and multiple partially necrotic skin lesions disseminated all over the entire body five days after returning from a trip to Colombia. The initial clinical suspicion of a tropical disease (leishmaniosis, systemic mycosis, or others) could not be confirmed. During the diagnostic workup, microbiological cultures of the skin biopsies and bronchoalveolar lavage revealed Pseudomonas aeruginosa, leading to a diagnosis of EG. Initial antibiotic treatment resulted in partial remission. However, the patient had to be re-admitted due to a relapse 3–4 weeks after the first episode. Finally, the patient was successfully treated with a combined approach consisting of antibiotics, recurrent surgical incisions, and administration of immunoglobulins. Conclusions In conclusion, EG should be considered as a differential diagnosis in immunosuppressed patients presenting with eschar-like skin ulcers. A combined treatment approach seems to be the best choice to achieve clinical cure and avoid relapse.

scholarly journals Prevalence of metallo-β-lactamase genes among Pseudomonas aeruginosa isolated from various clinical samples in China

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Wei Wang ◽  
Xiaoya Wang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Susceptibility ◽  
Ethylenediaminetetraacetic Acid ◽  
Carbapenem Resistance ◽  
Opportunistic Pathogen ◽  
Detection Methods ◽  
Clinical Samples ◽  
Routine Practice ◽  
Carbapenem Resistant ◽  
High Prevalence

AbstractBackgroundPseudomonas aeruginosa is an opportunistic pathogen which is associated with nosocomial infections and causes various diseases including urinary tract infection, pneumonia, soft-tissue infection and sepsis. The emergence of P. aeruginosa-acquired metallo-β-lactamase (MBL) is most worrisome and poses a serious threat during treatment and infection control. The objective of this study was to identify antibiotic susceptibility, phenotypic detection of MBL production and to determine the prevalence of MBL genes in carbapenem-resistant P. aeruginosa isolated from different clinical samples.MethodsA total of 329 non-duplicate P. aeruginosa isolated from various clinical samples from two hospitals in China between September 2017 and March 2019 were included in this study. Phenotypic detection of MBL was performed by the combined detection method using imipenem and imipenem-ethylenediaminetetraacetic acid (EDTA) discs. MBL-encoding genes including blaVIM-1, blaVIM-2, blaIMP-1, blaIMP-2, blaSPM-1, blaSIM, blaNDM-1 and blaGIM were detected by polymerase chain reaction (PCR).ResultsOf the 329 P. aeruginosa, majority of the isolates were resistant to imipenem (77.5%) followed by meropenem (64.7%). Of the 270 P. aeruginosa isolates tested, 149 (55.2%) isolates were found to be positive for MBL detection. Of the different samples, 57.8% (n = 26) of P. aeruginosa isolated from blood were found to be positive for MBL production. Of the various MBL genes, blaIMP-1 (28.2%) was the most predominant gene detected followed by blaVIM-2 (18.8%), blaVIM-1 (16.1%), blaNDM-1 (9.4%), blaIMP-2 (6.7%), blaSIM (6.0%), blaSPM-1 (4.0%) and blaGIM (1.3%) genes.ConclusionsThe high resistance of P. aeruginosa toward imipenem and meropenem and the high prevalence of blaIMP-1 and blaVIM-2 set the alarm on the increasing, perhaps the increased, carbapenem resistance. In addition to routine antibiotic susceptibility testings, our results emphasize the importance of both the phenotypic and genotypic MBL detection methods in routine practice for early detection of carbapenem resistance and to prevent further dissemination of this resistant pathogen.

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