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  1. AU="Barbara I Kazmierczak"
  2. AU=Gendron Joshua M
  3. AU="Klaaßen-Mielke, Renate"
  4. AU=Rao Saieesh A AU=Rao Saieesh A
  5. AU="Md. Arifur Rahman Munshi"
  6. AU=Gorbunova Vera
  7. AU="Mathias Uhlen"
  8. AU="Torrens, Alexa"
  9. AU="Moloney, E"
  10. AU="Pulawski, S."
  11. AU="Ustuner, Mehmet Cengiz"
  12. AU="Solozhentseva, Kristina"
  13. AU="Sitar, Cristian"
  14. AU="Ahmed, Md Firoz"
  15. AU=Goldberg Elad
  16. AU="Moskowitz, Jeremy D"
  17. AU="Mugunthan, Susithra Priyadarshni"
  18. AU="Matini, Lawrence"
  19. AU="Pourova, Radka"
  20. AU="Saxena, Shweta"
  21. AU="McGovern, Sophie"
  22. AU="Shuai An"
  23. AU="Kirill S. Golokhvast"
  24. AU="Cho, Kwang-Hwi"
  25. AU="Davitoiu, Dragos"
  26. AU=Templeman Charles
  27. AU="Attaluri, Anilchandra"
  28. AU="Cox, Ryan M"
  29. AU="Barua, Melissa"
  30. AU=Wong Ngai-Sze
  31. AU="Salgotra, Romesh Kumar"
  32. AU="Rossano, Adam J"
  33. AU="Pfeiffer, Christian"
  34. AU="Klostermann, Cynthia E."
  35. AU="Ivory, Joannie M"
  36. AU="Sooltangos, Aisha"
  37. AU="Marcia Adriana Poll"
  38. AU="Wenzel, Ross"
  39. AU="Wang, Ruihan"
  40. AU=Qing Enya AU=Qing Enya
  41. AU=Xu Jian AU=Xu Jian

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  1. Artikel ; Online: A conservative amino acid mutation in the master regulator FleQ renders Pseudomonas aeruginosa aflagellate.

    Ruchi Jain / Barbara I Kazmierczak

    PLoS ONE, Vol 9, Iss 5, p e

    2014  Band 97439

    Abstract: Flagellar-based motility plays a critical role in Pseudomonas aeruginosa pathogenesis, influencing both the establishment of bacterial infection and the host's response to the pathogen. Nonetheless, aflagellate clinical strains are often isolated from ... ...

    Abstract Flagellar-based motility plays a critical role in Pseudomonas aeruginosa pathogenesis, influencing both the establishment of bacterial infection and the host's response to the pathogen. Nonetheless, aflagellate clinical strains are often isolated from acutely and chronically infected patients and include the virulent laboratory strain PA103. We determined that PA103's aflagellate phenotype is the result of a single amino acid change (G240V) in the master flagellar regulator, FleQ. This mutation, which lies just outside the Walker B box of FleQ, abrogates the ability of FleQ to positively regulate flagellar gene expression. Reversal of this seemingly conservative amino acid substitution is sufficient to restore swimming motility to PA103, despite the presence of mutations in other flagellar genes of PA103. We also investigated the consequences of restoring flagellar assembly on PA103 virulence. Although a negative correlation between flagellar assembly and Type 3 secretion system (T3SS) expression has been reported previously, we did not observe downregulation of T3SS expression or function in Fla+ PA103. Restoration of flagellar assembly did, however, amplify IL-1 signals measured during murine pulmonary infection and was associated with increased bacterial clearance. These experiments suggest that loss of flagellar motility may primarily benefit PA103 by attenuating pathogen recognition and clearance during acute infection.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Interaction of the cyclic-di-GMP binding protein FimX and the Type 4 pilus assembly ATPase promotes pilus assembly.

    Ruchi Jain / Oleksii Sliusarenko / Barbara I Kazmierczak

    PLoS Pathogens, Vol 13, Iss 8, p e

    2017  Band 1006594

    Abstract: Type IVa pili (T4P) are bacterial surface structures that enable motility, adhesion, biofilm formation and virulence. T4P are assembled by nanomachines that span the bacterial cell envelope. Cycles of T4P assembly and retraction, powered by the ATPases ... ...

    Abstract Type IVa pili (T4P) are bacterial surface structures that enable motility, adhesion, biofilm formation and virulence. T4P are assembled by nanomachines that span the bacterial cell envelope. Cycles of T4P assembly and retraction, powered by the ATPases PilB and PilT, allow bacteria to attach to and pull themselves along surfaces, so-called "twitching motility". These opposing ATPase activities must be coordinated and T4P assembly limited to one pole for bacteria to show directional movement. How this occurs is still incompletely understood. Herein, we show that the c-di-GMP binding protein FimX, which is required for T4P assembly in Pseudomonas aeruginosa, localizes to the leading pole of twitching bacteria. Polar FimX localization requires both the presence of T4P assembly machine proteins and the assembly ATPase PilB. PilB itself loses its polar localization pattern when FimX is absent. We use two different approaches to confirm that FimX and PilB interact in vivo and in vitro, and further show that point mutant alleles of FimX that do not bind c-di-GMP also do not interact with PilB. Lastly, we demonstrate that FimX positively regulates T4P assembly and twitching motility by promoting the activity of the PilB ATPase, and not by stabilizing assembled pili or by preventing PilT-mediated retraction. Mutated alleles of FimX that no longer bind c-di-GMP do not allow rapid T4P assembly in these assays. We propose that by virtue of its high-affinity for c-di-GMP, FimX can promote T4P assembly when intracellular levels of this cyclic nucleotide are low. As P. aeruginosa PilB is not itself a high-affinity c-di-GMP receptor, unlike many other assembly ATPases, FimX may play a key role in coupling T4P mediated motility and adhesion to levels of this second messenger.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2017-08-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Structural insights into the career path between pre- and postgraduate physician-scientist training programs

    Christopher S Williams / Emily J Gallagher / Don C Rockey / Olujimi A Ajijola / Patrick J Hu / Barbara I Kazmierczak / Christopher D Kontos / Jatin M Vyas / Mone Zaidi / Kyu Y Rhee

    eLife, Vol

    2023  Band 12

    Abstract: The growing complexities of clinical medicine and biomedical research have clouded the career path for physician-scientists. In this perspective piece, we address one of the most opaque career stage transitions along the physician-scientist career path, ... ...

    Abstract The growing complexities of clinical medicine and biomedical research have clouded the career path for physician-scientists. In this perspective piece, we address one of the most opaque career stage transitions along the physician-scientist career path, the transition from medical school to research-focused internal medicine residency programs, or physician-scientist training programs (PSTPs). We present the perspectives of medical scientist training program (MSTP) and PSTP directors on critical features of PSTPs that can help trainees proactively align their clinical and scientific training for successful career development. We aim to provide both trainees and MSTP directors with a conceptual framework to better understand and navigate PSTPs. We also offer interview-specific questions to help trainees gather data and make informed decisions in choosing a residency program that best supports their career.
    Schlagwörter physician scientist ; PSTP ; training ; career ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 370
    Sprache Englisch
    Erscheinungsdatum 2023-10-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Modulation of flagellar rotation in surface-attached bacteria

    Maren Schniederberend / Jessica F Williams / Emilee Shine / Cong Shen / Ruchi Jain / Thierry Emonet / Barbara I Kazmierczak

    PLoS Pathogens, Vol 15, Iss 11, p e

    A pathway for rapid surface-sensing after flagellar attachment.

    2019  Band 1008149

    Abstract: Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa can initially attach ... ...

    Abstract Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa can initially attach to surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached and express surface-associated structures, such as Type IV pili, and behaviors, including twitching motility and biofilm initiation. P. aeruginosa that lack the GTPase FlhF assemble a randomly placed flagellum that is motile; however, we observed that these mutant bacteria show defects in biofilm formation comparable to those seen for non-motile, aflagellate bacteria. This phenotype was associated with altered behavior of ΔflhF bacteria immediately following surface-attachment. Forward and reverse genetic screens led to the discovery that FlhF interacts with FimV to control flagellar rotation at a surface, and implicated cAMP signaling in this pathway. Although cAMP controls many transcriptional programs in P. aeruginosa, known targets of this second messenger were not required to modulate flagellar rotation in surface-attached bacteria. Instead, alterations in switching behavior of the motor appeared to result from direct or indirect effects of cAMP on switch complex proteins and/or the stators associated with them.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2019-11-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Rampant Cheating by Pathogens?

    Ethan A Rundell / Saria A McKeithen-Mead / Barbara I Kazmierczak

    PLoS Pathogens, Vol 12, Iss 9, p e

    2016  Band 1005792

    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2016-09-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Pearls of wisdom for aspiring physician-scientist residency applicants and program directors

    Emily J. Gallagher / Don C. Rockey / Christopher D. Kontos / Jatin M. Vyas / Lawrence F. Brass / Patrick J. Hu / Carlos M. Isales / Olujimi A. Ajijola / W. Kimryn Rathmell / Paul R. Conlin / Robert A. Baiocchi / Barbara I. Kazmierczak / Myles H. Akabas / Christopher S. Williams

    JCI Insight, Vol 7, Iss

    2022  Band 6

    Abstract: Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant ...

    Abstract Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant competitiveness for these programs would be enhanced, and unnecessary trainee anxiety relieved, by a clear understanding of what factors define a successful PSTP matriculant. Such information would also be invaluable to PSTP directors and would allow benchmarking of their admissions processes with peer programs. We conducted a survey of PSTP directors across the US to understand the importance they placed on components of PSTP applications. Of 41 survey respondents, most were from internal medicine and pediatrics residency programs. Of all components in the application, two elements were considered very important by a majority of PSTP directors: (a) having one or more first-author publications and (b) the thesis advisor’s letter. Less weight was consistently placed on factors often considered more relevant for non-physician-scientist postgraduate applicants — such as US Medical Licensing Examination scores, awards, and leadership activities. The data presented here highlight important metrics for PSTP applicants and directors and suggest that indicators of scientific productivity and commitment to research outweigh traditional quantitative measures of medical school performance.
    Schlagwörter Medicine ; R
    Thema/Rubrik (Code) 020
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag American Society for Clinical investigation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Host suppression of quorum sensing during catheter-associated urinary tract infections

    Stephanie J. Cole / Cherisse L. Hall / Maren Schniederberend / John M. Farrow III / Jonathan R. Goodson / Everett C. Pesci / Barbara I. Kazmierczak / Vincent T. Lee

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Band 8

    Abstract: Pseudomonas aeruginosa can cause chronic infections on medical devices by forming biofilms, a process regulated by quorum sensing (QS). Here, the authors show that P. aeruginosa is unable to perceive QS signals in the presence of either host urine or ... ...

    Abstract Pseudomonas aeruginosa can cause chronic infections on medical devices by forming biofilms, a process regulated by quorum sensing (QS). Here, the authors show that P. aeruginosa is unable to perceive QS signals in the presence of either host urine or urea, and clinical isolates are often defective in QS.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2018-10-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Host suppression of quorum sensing during catheter-associated urinary tract infections

    Stephanie J. Cole / Cherisse L. Hall / Maren Schniederberend / John M. Farrow III / Jonathan R. Goodson / Everett C. Pesci / Barbara I. Kazmierczak / Vincent T. Lee

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Band 8

    Abstract: Pseudomonas aeruginosa can cause chronic infections on medical devices by forming biofilms, a process regulated by quorum sensing (QS). Here, the authors show that P. aeruginosa is unable to perceive QS signals in the presence of either host urine or ... ...

    Abstract Pseudomonas aeruginosa can cause chronic infections on medical devices by forming biofilms, a process regulated by quorum sensing (QS). Here, the authors show that P. aeruginosa is unable to perceive QS signals in the presence of either host urine or urea, and clinical isolates are often defective in QS.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2018-10-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: The ability of virulence factor expression by Pseudomonas aeruginosa to predict clinical disease in hospitalized patients.

    Michel Ledizet / Thomas S Murray / Sailaja Puttagunta / Martin D Slade / Vincent J Quagliarello / Barbara I Kazmierczak

    PLoS ONE, Vol 7, Iss 11, p e

    2012  Band 49578

    Abstract: Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes hospital acquired colonization and infection. Accurate identification of host and bacterial factors associated with infection could aid treatment decisions for patients with P. ... ...

    Abstract Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes hospital acquired colonization and infection. Accurate identification of host and bacterial factors associated with infection could aid treatment decisions for patients with P. aeruginosa cultured from clinical sites.We identified a prospective cohort of 248 hospitalized patients with positive P. aeruginosa cultures. Clinical data were analyzed to determine whether an individual met predefined criteria for infection versus colonization. P. aeruginosa isolates were tested for the expression of multiple phenotypes previously associated with virulence in animal models and humans. Logistic regression models were constructed to determine the degree of association between host and bacterial factors with P. aeruginosa infection of the bloodstream, lung, soft tissue and urinary tract.One host factor (i.e. diabetes mellitus), and one bacterial factor, a Type 3 secretion system positive phenotype, were significantly associated with P. aeruginosa infection in our cohort. Subgroup analysis of patients with P. aeruginosa isolated from the urinary tract revealed that the presence of a urinary tract catheter or stent was an additional factor for P. aeruginosa infection.Among hospitalized patients with culture-documented P. aeruginosa, infection is more likely to be present in those with diabetes mellitus and those harboring a Type 3 secretion positive bacterial strain.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: The carbon monoxide releasing molecule CORM-2 attenuates Pseudomonas aeruginosa biofilm formation.

    Thomas S Murray / Chinweike Okegbe / Yuan Gao / Barbara I Kazmierczak / Roberto Motterlini / Lars E P Dietrich / Emanuela M Bruscia

    PLoS ONE, Vol 7, Iss 4, p e

    2012  Band 35499

    Abstract: Chronic infections resulting from biofilm formation are difficult to eradicate with current antimicrobial agents and consequently new therapies are needed. This work demonstrates that the carbon monoxide-releasing molecule CORM-2, previously shown to ... ...

    Abstract Chronic infections resulting from biofilm formation are difficult to eradicate with current antimicrobial agents and consequently new therapies are needed. This work demonstrates that the carbon monoxide-releasing molecule CORM-2, previously shown to kill planktonic bacteria, also attenuates surface-associated growth of the gram-negative pathogen Pseudomonas aeruginosa by both preventing biofilm maturation and killing bacteria within the established biofilm. CORM-2 treatment has an additive effect when combined with tobramycin, a drug commonly used to treat P. aeruginosa lung infections. CORM-2 inhibited biofilm formation and planktonic growth of the majority of clinical P. aeruginosa isolates tested, for both mucoid and non-mucoid strains. While CORM-2 treatment increased the production of reactive oxygen species by P. aeruginosa biofilms, this increase did not correlate with bacterial death. These data demonstrate that CO-RMs possess potential novel therapeutic properties against a subset of P. aeruginosa biofilm related infections.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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