scholarly journals Antipathogenic Compounds That Are Effective at Very Low Concentrations and Have Both Antibiofilm and Antivirulence Effects against Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Hyeon-Ji Hwang ◽  
Heejeong Choi ◽  
Sojeong Hong ◽  
Hyung Ryong Moon ◽  
Joon-Hee Lee
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Biofilm Formation ◽  
Human Pathogen ◽  
Chemical Library ◽  
Content Type ◽  
Low Concentrations

Many antibiotics are increasingly losing their efficacy due to antibiotic resistance mediated by biofilm formation. In this study, we screened a synthetic chemical library and discovered several compounds that have both antivirulence and antibiofilm effects against Pseudomonas aeruginosa , a notorious human pathogen.

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 Role of Intracellular Proteases in the Antibiotic Resistance, Motility, and Biofilm Formation of Pseudomonas aeruginosa

2011 ◽  
Vol 56 (2) ◽  
pp. 1128-1132 ◽  
Author(s):  
Lucía Fernández ◽  
Elena B. M. Breidenstein ◽  
Diana Song ◽  
Robert E. W. Hancock
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Biofilm Formation ◽  
Regulatory Networks ◽  
Swarming Motility ◽  
Content Type ◽  
Adverse Conditions ◽  
Related Proteins ◽  
Intracellular Proteases

ABSTRACTPseudomonas aeruginosapossesses complex regulatory networks controlling virulence and survival under adverse conditions, including antibiotic pressure, which are interconnected and share common regulatory proteins. Here, we screen a panel of 13 mutants defective in intracellular proteases and demonstrate that, in addition to the known alterations in Lon and AsrA mutants, mutation of three protease-related proteins PfpI, ClpS, and ClpP differentially affected antibiotic resistance, swarming motility, and biofilm formation.

scholarly journals Evolution of Antibiotic Tolerance Shapes Resistance Development in Chronic Pseudomonas aeruginosa Infections

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Isabella Santi ◽  
Pablo Manfredi ◽  
Enea Maffei ◽  
Adrian Egli ◽  
Urs Jenal
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Prolonged Exposure ◽  
Drug Tolerance ◽  
Antibiotic Tolerance ◽  
Human Pathogen ◽  
Chronic Infections ◽  
Resistance Development ◽  
Content Type

ABSTRACT The widespread use of antibiotics promotes the evolution and dissemination of resistance and tolerance mechanisms. To assess the relevance of tolerance and its implications for resistance development, we used in vitro evolution and analyzed the inpatient microevolution of Pseudomonas aeruginosa, an important human pathogen causing acute and chronic infections. We show that the development of tolerance precedes and promotes the acquisition of resistance in vitro, and we present evidence that similar processes shape antibiotic exposure in human patients. Our data suggest that during chronic infections, P. aeruginosa first acquires moderate drug tolerance before following distinct evolutionary trajectories that lead to high-level multidrug tolerance or to antibiotic resistance. Our studies propose that the development of antibiotic tolerance predisposes bacteria for the acquisition of resistance at early stages of infection and that both mechanisms independently promote bacterial survival during antibiotic treatment at later stages of chronic infections. IMPORTANCE Over the past decades, pan-resistant strains of major bacterial pathogens have emerged and have rendered clinically available antibiotics ineffective, putting at risk many of the major achievements of modern medicine, including surgery, cancer therapy, and organ transplantation. A thorough understanding of processes leading to the development of antibiotic resistance in human patients is thus urgently needed. We show that drug tolerance, the ability of bacteria to survive prolonged exposure to bactericidal antibiotics, rapidly evolves in the opportunistic human pathogen Pseudomonas aeruginosa upon recurrent exposures to antibiotics. Our studies show that tolerance protects P. aeruginosa against different classes of antibiotics and that it generally precedes and promotes resistance development. The rapid evolution of tolerance during treatment regimens may thus act as a strong driving force to accelerate antibiotic resistance development. To successfully counter resistance, diagnostic measures and novel treatment strategies will need to incorporate the important role of antibiotic tolerance.

scholarly journals Pseudomonas aeruginosa Condensins Support Opposite Differentiation States

2016 ◽  
Vol 198 (21) ◽  
pp. 2936-2944 ◽  
Author(s):  
Hang Zhao ◽  
April L. Clevenger ◽  
Jerry W. Ritchey ◽  
Helen I. Zgurskaya ◽  
Valentin V. Rybenkov
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Competitive Growth ◽  
Human Pathogen ◽  
Functional Protein ◽  
Content Type ◽  
Bacterial Physiology ◽  
Growth Defects ◽  
Bacterial Pathogenicity ◽  
Opportunistic Human Pathogen

ABSTRACTCondensins play a key role in global chromosome packing.Pseudomonas aeruginosaencodes two condensins, SMC-ScpAB and MksBEF. We report here that the two proteins are involved in the differentiation of the bacterium and impose opposite physiological states. The inactivation of SMC induced a state characterized by increased adhesion to surfaces as well as defects in competitive growth and colony formation. In contrast, MksB-deficient cells were impaired in biofilm formation with no obvious defects during planktonic growth. The phenotype of the double mutant was dominated by the absence of MksB, indicating that the observed growth defects are regulatory in their nature rather than structural. ATPase mutations recapitulated many of the phenotypes of the condensins, indicating their requirement for a functional protein. Additionally, inactivation of condensins dramatically reduced the virulence of the bacterium in a murine model of lung infection. These data demonstrate that condensins are involved in the differentiation ofP. aeruginosaand reveal their importance for pathogenicity.IMPORTANCEAdaptation and differentiation play key roles in bacterial pathogenicity. InPseudomonas aeruginosa, an opportunistic human pathogen, these processes are mediated by the activity of an intricate regulatory network. We describe here novel members of this network, condensins. We show that the twoP. aeruginosacondensins specialize in the establishment of the sessile and planktonic states of the bacterium. Whereas condensins have well-established roles in global chromosome organization, their roles in regulating bacterial physiology have remained unknown. Our data indicate that the two programs may be linked. We further show that condensins are essential for the pathogenicity ofP. aeruginosa.

scholarly journals Cyclic Di-GMP Signaling Contributes to Pseudomonas aeruginosa-Mediated Catheter-Associated Urinary Tract Infection

2015 ◽  
Vol 198 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Stephanie J. Cole ◽  
Vincent T. Lee
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Biofilm Formation ◽  
Bacterial Burden ◽  
Wild Type ◽  
Gram Negative ◽  
Content Type ◽  
Low Concentrations

ABSTRACTBis-(3′-5′) cyclic dimeric GMP (c-di-GMP) controls the lifestyle transition between the sessile and motile states in many Gram-negative bacteria, including the opportunistic human pathogenPseudomonas aeruginosa. Under laboratory conditions, high concentrations of c-di-GMP decrease motility and promote biofilm formation, while low concentrations of c-di-GMP promote motility and decease biofilm formation. Here we sought to determine the contribution of c-di-GMP signaling to biofilm formation duringP. aeruginosa-mediated catheter-associated urinary tract infection (CAUTI). Using a murine CAUTI model, a decrease in CFU was detected in the bladders and kidneys of mice infected with strains overexpressing the phosphodiesterases (PDEs) encoded byPA3947andPA2133compared to those infected with wild-typeP. aeruginosa. Conversely, overexpression of the diguanylate cyclases (DGCs) encoded byPA3702andPA1107increased the number of bacteria in bladder and significantly increased dissemination of bacteria to the kidneys compared to wild-type infection. To determine which of the DGCs and PDEs contribute to c-di-GMP signaling during infection, a panel of PA14 in-frame deletion mutants lacking DGCs and PDEs were tested in the CAUTI model. Results from these infections revealed five mutants, three containing GGDEF domains (ΔPA14_26970, ΔPA14_72420, and ΔsiaD) and two containing dual GGDEF-EAL domains (ΔmorAand ΔPA14_07500), with decreased colonization of the bladder and dissemination to the kidneys. These results indicate that c-di-GMP signaling influencesP. aeruginosa-mediated biofilms during CAUTI.IMPORTANCEBiofilm-based infections are an important cause of nosocomial infections, since they resist the immune response and traditional antibiotic treatment. Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in many Gram-negative pathogens, includingPseudomonas aeruginosa. Here we determined the contribution of c-di-GMP signaling to catheter-associated urinary tract infection (CAUTI), an animal model of biofilm-based infection.P. aeruginosawith elevated levels of c-di-GMP during the initial infection produces an increased bacterial burden in the bladder and kidneys. Conversely, low concentrations of c-di-GMP decreased the bacterial burden in the bladder and kidneys. We screened a library of mutants with mutations in genes regulating c-di-GMP signaling and found several mutants that altered colonization of the urinary tract. This study implicates c-di-GMP signaling during CAUTI.

scholarly journals Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Bhavani Manivannan ◽  
Niranjana Mahalingam ◽  
Sudhir Jadhao ◽  
Amrita Mishra ◽  
Pravin Nilawe ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Genome Assembly ◽  
Biofilm Formation ◽  
Draft Genome ◽  
Drug Resistant ◽  
Draft Genome Assembly ◽  
Extensively Drug Resistant ◽  
History Of ◽  
Urinary Tuberculosis

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.

scholarly journals Specific Control of Pseudomonas aeruginosa Surface-Associated Behaviors by Two c-di-GMP Diguanylate Cyclases

mBio ◽  
2010 ◽  
Vol 1 (4) ◽  
Author(s):  
Judith H. Merritt ◽  
Dae-Gon Ha ◽  
Kimberly N. Cowles ◽  
Wenyun Lu ◽  
Diana K. Morales ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Extracellular Polysaccharide ◽  
Diguanylate Cyclase ◽  
Flagellar Motility ◽  
Critical Question ◽  
Cyclic Diguanylate ◽  
Critical Signal ◽  
Content Type ◽  
Wide Range

ABSTRACT The signaling nucleotide cyclic diguanylate (c-di-GMP) regulates the transition between motile and sessile growth in a wide range of bacteria. Understanding how microbes control c-di-GMP metabolism to activate specific pathways is complicated by the apparent multifold redundancy of enzymes that synthesize and degrade this dinucleotide, and several models have been proposed to explain how bacteria coordinate the actions of these many enzymes. Here we report the identification of a diguanylate cyclase (DGC), RoeA, of Pseudomonas aeruginosa that promotes the production of extracellular polysaccharide (EPS) and contributes to biofilm formation, that is, the transition from planktonic to surface-dwelling cells. Our studies reveal that RoeA and the previously described DGC SadC make distinct contributions to biofilm formation, controlling polysaccharide production and flagellar motility, respectively. Measurement of total cellular levels of c-di-GMP in ∆roeA and ∆sadC mutants in two different genetic backgrounds revealed no correlation between levels of c-di-GMP and the observed phenotypic output with regard to swarming motility and EPS production. Our data strongly argue against a model wherein changes in total levels of c-di-GMP can account for the specific surface-related phenotypes of P. aeruginosa. IMPORTANCE A critical question in the study of cyclic diguanylate (c-di-GMP) signaling is how the bacterial cell integrates contributions of multiple c-di-GMP-metabolizing enzymes to mediate its cognate functional outputs. One leading model suggests that the effects of c-di-GMP must, in part, be localized subcellularly. The data presented here show that the phenotypes controlled by two different diguanylate cyclase (DGC) enzymes have discrete outputs despite the same total level of c-di-GMP. These data support and extend the model in which localized c-di-GMP signaling likely contributes to coordination of the action of the multiple proteins involved in the synthesis, degradation, and/or binding of this critical signal.

Pseudomonas aeruginosa transition from environmental generalist to human pathogen

2021 ◽  
Vol 13 (1) ◽  
pp. 11
Author(s):  
Gabriela Vasco ◽  
Gabriel Trueba
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Human Body ◽  
Biofilm Formation ◽  
Reduction Reaction ◽  
Human Pathogen ◽  
Opportunistic Bacteria ◽  
Oxidation Reduction ◽  
Mammalian Tissues ◽  
Oxidation Reduction Reaction ◽  
Source Sink

Opportunistic bacteria Pseudomonas aeruginosa is one of the major concerns as an etiological agent of nosocomial infections in humans. Many virulence factors used to colonize the human body are the same as those used by P. aeruginosa to thrive in the environment such as membrane transport, biofilm formation, oxidation/reduction reaction, among others. P. aeruginosa origin is mainly from the environment, the adaptation to mammalian tissues may follow a source-sink evolution model; the environment is the source of many lineages, some of them capable of adaptation to the human body. Some lineages may adapt to humans and go through reductive evolution in which some genes are lost.  The understanding of this process may be critical to implement better methods to control outbreaks in hospitals.

scholarly journals Antimicrobial Resistance and Biofilm Formation of Pseudomonas aeruginosa

10.3823/846 ◽  
2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Abdelraouf A Elmanama ◽  
Suhaila Al-Sheboul ◽  
Renad I Abu-Dan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Quorum Sensing ◽  
Bacterial Adhesion ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Developmental Stages ◽  
Infection Site ◽  
Major Virulence Factor

Abstract Pseudomonas aeruginosa threatens patient’s care. It is considered as the most complicated health care associated pathogen to be eliminated from infection site. The biofilm forming ability of P. aeruginosa, being a major virulence factor for most pathogenic microorganism, protects it from host immunity and contribute to antibiotic resistance of this organism. It is estimated that about 80% of infectious diseases are due to biofilm mode of growth. Biofilm forming ability of bacteria imparts antimicrobial resistance that leads to many persistent and chronic bacterial infections. The world is becoming increasingly under the threat of entering the “post-antibiotic era”, an era in which the rate of death from bacterial infections is higher than from cancer. This review focus on P. aeruginosa biofilm forming ability; definition, developmental stages, and significance. In addition, the quorum sensing and the antibiotic resistance of this pathogen is discussed. Keywords: Biofilm; bacterial adhesion; Pseudomonas aeruginosa; antimicrobial resistance; quorum sensing.

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