scholarly journals Suicidal chemotaxis in bacteria

2021 ◽  
Author(s):  
Nuno M Oliveira ◽  
James H R Wheeler ◽  
Cyril Deroy ◽  
Sean C Booth ◽  
Edmond J Walsh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Microfluidic Devices ◽  
Chemical Compounds ◽  
Opportunistic Pathogen ◽  
Twitching Motility ◽  
Direct Response ◽  
Spatial Gradients ◽  
Migrating Cells

Bacteria commonly live in communities on surfaces where steep gradients of antibiotics and other chemical compounds routinely occur. While many species of bacteria can move on surfaces, we know surprisingly little about how such antibiotic gradients affect cell motility. Here we study the behaviour of the opportunistic pathogen Pseudomonas aeruginosa in stable spatial gradients of a range of antibiotics by tracking thousands of cells in microfluidic devices as they form biofilms. Unexpectedly, these experiments reveal that individual bacteria use pili-based ('twitching') motility to actively navigate towards regions with higher antibiotic concentrations. Our analyses suggest that this biased migration is driven, at least in part, by a direct response to the antibiotics. Migrating cells can reach antibiotic concentrations hundreds of times higher than their minimum inhibitory concentration in a few hours and remain highly motile. However, isolating these cells - using fluid-walled microfluidic devices that can be reconfigured in situ - suggests that these bacteria are terminal and not able to reproduce. In spite of moving towards their death, we show that migrating cells are capable of entering a suicidal program to release bacteriocins that are used to kill other bacteria. Our work suggests that bacteria respond to antibiotics as if they come from a competing colony growing in the neighbourhood, inducing them to invade and attack. As a result, clinical antibiotics have the potential to serve as a bait that lures bacteria to their death.

scholarly journals Disparate Subcellular Localization Patterns of Pseudomonas aeruginosa Type IV Pilus ATPases Involved in Twitching Motility

2005 ◽  
Vol 187 (3) ◽  
pp. 829-839 ◽  
Author(s):  
Poney Chiang ◽  
Marc Habash ◽  
Lori L. Burrows
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Fluorescent Protein ◽  
Protein Localization ◽  
Yellow Fluorescent Protein ◽  
Distribution Patterns ◽  
Opportunistic Pathogen ◽  
Twitching Motility ◽  
Polar Localization ◽  
Type Iv ◽  
And Function

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa expresses polar type IV pili (TFP), which are responsible for adhesion to various materials and twitching motility on surfaces. Twitching occurs by alternate extension and retraction of TFP, which arise from assembly and disassembly of pilin subunits at the base of the pilus. The ATPase PilB promotes pilin assembly, while the ATPase PilT or PilU or both promote pilin dissociation. Fluorescent fusions to two of the three ATPases (PilT and PilU) were functional, as shown by complementation of the corresponding mutants. PilB and PilT fusions localized to both poles, while PilU fusions localized only to the piliated pole. To identify the portion of the ATPases required for localization, sequential C-terminal deletions of PilT and PilU were generated. The conserved His and Walker B boxes were dispensable for polar localization but were required for twitching motility, showing that localization and function could be uncoupled. Truncated fusions that retained polar localization maintained their distinctive distribution patterns. To dissect the cellular factors involved in establishing polarity, fusion protein localization was monitored with a panel of TFP mutants. The localization of yellow fluorescent protein (YFP)-PilT and YFP-PilU was independent of the subunit PilA, other TFP ATPases, and TFP-associated proteins previously shown to be associated with the membrane or exhibiting polar localization. In contrast, YFP-PilB exhibited diffuse cytoplasmic localization in a pilC mutant, suggesting that PilC is required for polar localization of PilB. Finally, localization studies performed with fluorescent ATPase chimeras of PilT and PilU demonstrated that information responsible for the characteristic localization patterns of the ATPases likely resides in their N termini.

Reservoirs of resistance: polymyxin resistance in veterinary-associated companion animal isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 185 (7) ◽  
pp. 206-206 ◽  
Author(s):  
Andrea Scott ◽  
Sian Pottenger ◽  
Dorina Timofte ◽  
Matthew Moore ◽  
Laura Wright ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Respiratory Infections ◽  
Companion Animals ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Potential Reservoir ◽  
Human Infections ◽  
Animal Isolates

BackgroundPseudomonas aeruginosa is an opportunistic pathogen and a major cause of infections. Widespread resistance in human infections are increasing the use of last resort antimicrobials such as polymyxins. However, these have been used for decades in veterinary medicine. Companion animals are an understudied source of antimicrobial resistant P. aeruginosa isolates. This study evaluated the susceptibility of P. aeruginosa veterinary isolates to polymyxins to determine whether the veterinary niche represents a potential reservoir of resistance genes for pathogenic bacteria in both animals and humans.Methods and resultsClinical P. aeruginosa isolates (n=24) from UK companion animals were compared for antimicrobial susceptibility to a panel of human-associated isolates (n=37). Minimum inhibitory concentration (MIC) values for polymyxin B and colistin in the companion animals was significantly higher than in human isolates (P=0.033 and P=0.013, respectively). Genotyping revealed that the veterinary isolates were spread throughout the P. aeruginosa population, with shared array types from human infections such as keratitis and respiratory infections, suggesting the potential for zoonotic transmission. Whole genome sequencing revealed mutations in genes associated with polymyxin resistance and other antimicrobial resistance-related genes.ConclusionThe high levels of resistance to polymyxin shown here, along with genetic similarities between some human and animal isolates, together suggest a need for sustained surveillance of this veterinary niche as a potential reservoir for resistant, clinically relevant bacteria in both animals and humans.

scholarly journals Cyclic AMP-Independent Control of Twitching Motility in Pseudomonas aeruginosa

2017 ◽  
Vol 199 (16) ◽  
Author(s):  
Ryan N. C. Buensuceso ◽  
Martin Daniel-Ivad ◽  
Sara L. N. Kilmury ◽  
Tiffany L. Leighton ◽  
Hanjeong Harvey ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Response Regulator ◽  
Opportunistic Pathogen ◽  
Regulatory Elements ◽  
Twitching Motility ◽  
Camp Phosphodiesterase ◽  
Content Type ◽  
Polar Localization ◽  
Camp Levels

ABSTRACT FimV is a Pseudomonas aeruginosa inner membrane hub protein that modulates levels of the second messenger, cyclic AMP (cAMP), through the activation of adenylate cyclase CyaB. Although type IVa pilus (T4aP)-dependent twitching motility is modulated by cAMP levels, mutants lacking FimV are twitching impaired, even when exogenous cAMP is provided. Here we further define FimV's cAMP-dependent and -independent regulation of twitching. We confirmed that the response regulator of the T4aP-associated Chp chemotaxis system, PilG, requires both FimV and the CyaB regulator, FimL, to activate CyaB. However, in cAMP-replete backgrounds—lacking the cAMP phosphodiesterase CpdA or the CheY-like protein PilH or expressing constitutively active CyaB—pilG and fimV mutants failed to twitch. Both cytoplasmic and periplasmic domains of FimV were important for its cAMP-dependent and -independent roles, while its septal peptidoglycan-targeting LysM motif was required only for twitching motility. Polar localization of the sensor kinase PilS, a key regulator of transcription of the major pilin, was FimV dependent. However, unlike its homologues in other species that localize flagellar system components, FimV was not required for swimming motility. These data provide further evidence to support FimV's role as a key hub protein that coordinates the polar localization and function of multiple structural and regulatory proteins involved in P. aeruginosa twitching motility. IMPORTANCE Pseudomonas aeruginosa is a serious opportunistic pathogen. Type IVa pili (T4aP) are important for its virulence, because they mediate dissemination and invasion via twitching motility and are involved in surface sensing, which modulates pathogenicity via changes in cAMP levels. Here we show that the hub protein FimV and the response regulator of the Chp system, PilG, regulate twitching independently of their roles in the modulation of cAMP synthesis. These functions do not require the putative scaffold protein FimL, proposed to link PilG with FimV. PilG may regulate asymmetric functioning of the T4aP system to allow for directional movement, while FimV appears to localize both structural and regulatory elements—including the PilSR two-component system—to cell poles for optimal function.

scholarly journals Mechanotaxis directs Pseudomonas aeruginosa twitching motility

2021 ◽  
Author(s):  
Marco J. Kühn ◽  
Lorenzo Talà ◽  
Yuki Inclan ◽  
Ramiro Patino ◽  
Xavier Pierrat ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Cells ◽  
Opportunistic Pathogen ◽  
Type Iv Pili ◽  
Twitching Motility ◽  
Response Regulators ◽  
Spatially Resolved ◽  
Type Iv ◽  
Mechanical Signal ◽  
Chp System

AbstractThe opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili. Single cells twitch by successive pili extension, attachment and retraction. However, whether and how single cells control twitching migration remains unclear. We discovered that P. aeruginosa actively directs twitching in the direction of mechanical input from type IV pili, in a process we call mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. On surfaces, Chp senses type IV pili attachment at one pole thereby sensing a spatially-resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. This distinct localization of response regulators establishes a signaling landscape known as local-excitation, global-inhibition in higher order organisms, identifying a conserved strategy to transduce spatially-resolved signals. Our discovery finally resolves the function of the Chp system and expands our view of the signals regulating motility.

scholarly journals Discovery and Characterization of Chemical Compounds That Inhibit the Function of Aspartyl-tRNA Synthetase from Pseudomonas aeruginosa

2017 ◽  
Vol 23 (3) ◽  
pp. 294-301 ◽  
Author(s):  
Araceli Corona ◽  
Stephanie O. Palmer ◽  
Regina Zamacona ◽  
Benjamin Mendez ◽  
Frank B. Dean ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aspartic Acid ◽  
Cell Cultures ◽  
Human Cell ◽  
Efflux Pump ◽  
Chemical Compounds ◽  
Opportunistic Pathogen ◽  
Trna Synthetase ◽  
Bacterial Strains ◽  
Human Cell Cultures

Pseudomonas aeruginosa, an opportunistic pathogen, is highly susceptible to developing resistance to multiple antibiotics. The gene encoding aspartyl-tRNA synthetase (AspRS) from P. aeruginosa was cloned and the resulting protein characterized. AspRS was kinetically evaluated, and the KM values for aspartic acid, ATP, and tRNA were 170, 495, and 0.5 μM, respectively. AspRS was developed into a screening platform using scintillation proximity assay (SPA) technology and used to screen 1690 chemical compounds, resulting in the identification of two inhibitory compounds, BT02A02 and BT02C05. The minimum inhibitory concentrations (MICs) were determined against nine clinically relevant bacterial strains, including efflux pump mutant and hypersensitive strains of P. aeruginosa. The compounds displayed broad-spectrum antibacterial activity and inhibited growth of the efflux and hypersensitive strains with MICs of 16 μg/mL. Growth of wild-type strains were unaffected, indicating that efflux was likely responsible for this lack of activity. BT02A02 did not inhibit growth of human cell cultures at any concentration. However, BT02C05 did inhibit human cell cultures with a cytotoxicity concentration (CC50) of 61.6 μg/mL. The compounds did not compete with either aspartic acid or ATP for binding AspRS, indicating that the mechanism of action of the compound occurs outside the active site of aminoacylation.

scholarly journals Minimum Inhibitory Concentration of Ciprofloxacin against Pseudomonas Aeruginosa in the Presence of the Efflux Inhibitor Phenylalanine-arginine Beta-naphthylamide

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Fatemeh Abbasi ◽  
Saber Yusefi ◽  
Shohreh Afshar Yavar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Minimum Inhibitory Concentration ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Opportunistic Pathogen ◽  
Outpatient Clinics ◽  
Multi Drug Resistance ◽  
Efflux System ◽  
Concentration Test ◽  
Multiple Drugs

Introduction: Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen causing infections in patients staying in the hospital and is resistant to multiple drugs. This study investigated the resistance to ciprofloxacin by the efflux system of Pseudomonas aeruginosa.Materials and Methods: For this purpose, the inhibitor of the efflux system phenylalanine-arginine beta-naphthylamide was used. In this study, 135 isolates of Pseudomonas aeruginosa were collected from the hospitalized patients of Imam Khomeini Hospital and outpatient clinics in Urmia during a ten-month period from June 2015 to March 2016. These isolates were re-identified by standard microbiological and biochemical methods. Finally, 51 isolates were selected for antibiotic susceptibility testing.Results: According to the antibiogram test, the Pseudomonas aeruginosa isolates exhibited highest resistance against ciprofloxacin (90.2%), tobramycin (88.2%), and gentamycin (86.3%) and the highest sensitivity towards colistin (76.4%), and imipenem (72.5%). The 51 isolates, which were selected for the minimum inhibitory concentration test, had multi-drug resistance regulators.Conclusion: The discovery and development of the efflux system inhibitors is an important strategy to deal with bacterial infections.

scholarly journals Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa

2017 ◽  
Vol 13 (5) ◽  
pp. e1006392 ◽  
Author(s):  
Jianfang Li ◽  
Matteo M. E. Metruccio ◽  
David J. Evans ◽  
Suzanne M. J. Fleiszig
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Twitching Motility

scholarly journals Correction: Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa

2017 ◽  
Vol 13 (9) ◽  
pp. e1006612 ◽  
Author(s):  
Jianfang Li ◽  
Matteo M. E. Metruccio ◽  
Benjamin E. Smith ◽  
David J. Evans ◽  
Suzanne M. J. Fleiszig
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Twitching Motility

scholarly journals Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 208 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Panchanathan Manivasagan ◽  
Jang-Won Lee ◽  
Dung Pham ◽  
Junghwan Oh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Brown Seaweed ◽  
Opportunistic Pathogen ◽  
Biofilm Inhibition ◽  
Transmission Electron ◽  
Inhibition Concentration ◽  
Life Threatening

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

scholarly journals Mechanotaxis directs Pseudomonas aeruginosa twitching motility

2021 ◽  
Vol 118 (30) ◽  
pp. e2101759118
Author(s):  
Marco J. Kühn ◽  
Lorenzo Talà ◽  
Yuki F. Inclan ◽  
Ramiro Patino ◽  
Xavier Pierrat ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Cells ◽  
Opportunistic Pathogen ◽  
Group Behavior ◽  
Twitching Motility ◽  
Response Regulators ◽  
Spatially Resolved ◽  
Type Iv ◽  
Mechanical Signal ◽  
Global Inhibition

The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili (T4P). Single cells twitch by sequential T4P extension, attachment, and retraction. How single cells coordinate T4P to efficiently navigate surfaces remains unclear. We demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from T4P in a process called mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. Collisions between twitching cells stimulate reversals, but Chp mutants either always or never reverse. As a result, while wild-type cells colonize surfaces uniformly, collision-blind Chp mutants jam, demonstrating a function for mechanosensing in regulating group behavior. On surfaces, Chp senses T4P attachment at one pole, thereby sensing a spatially resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization, inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local excitation–global inhibition in higher-order organisms, identifying a conserved strategy to transduce spatially resolved signals.

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