Daniel Pletzer

Daniel Pletzer
University of Otago · Department of Microbiology and Immunology

PhD
fighting antimicrobial resistance and infectious diseases

About

88
Publications
12,040
Reads
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1,519
Citations
Introduction
My research is focused on recalcitrant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens; especially hard-to-treat clinical isolates involved in multidrug resistance, biofilm infections and persistence. I am especially interested in Gram-negative bacteria that have been categorized as "critical" pathogens by WHO (pathogens where antibiotics are urgently needed). Find out more: pletzerlab.com
Additional affiliations
November 2019 - February 2022
University of Otago
Position
  • Lecturer / Senior Lecturer
July 2015 - October 2019
University of British Columbia - Vancouver
Position
  • Postdoctoral Fellow
June 2014 - June 2015
Jacobs University
Position
  • Postdoctoral Fellow
Description
  • Membrane proteins and peptide ABC transporters in Pseudomonas aeruginosa
Education
July 2011 - May 2014
Jacobs University
Field of study
  • Microbiology
September 2009 - June 2011
Jacobs University
Field of study
  • Molecular Genetics and Microbiology
September 2006 - July 2009
Fachhochschule Oberösterreich
Field of study
  • Bioinformatics

Publications

Publications (88)
Article
Full-text available
Only a few, relatively cumbersome animal models enable long-term Gram-negative bacterial infections that mimic human situations, where untreated infections can last for weeks. Here, we describe a simple murine cutaneous abscess model that enables chronic or progressive infections, depending on the subcutaneously injected bacterial strain. In this m...
Article
Full-text available
Author summary There has been enormous publicity about the inexorable rise of resistance and the dearth of new therapies. However less attention has been placed on adaptively multidrug-resistant high density bacterial infections for which antibiotics are highly used but no effective therapies currently exist. Here we have provided new hope for this...
Article
Full-text available
Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) U...
Article
Full-text available
Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) are opportunistic pathogens that are most commonly co‐isolated from chronic wounds and the sputum of cystic fibrosis patients. Over the last few years, there have been plenty of contrasting results from studies involving P. aeruginosa and S. aureus co‐cultures. The general concept that P. a...
Article
Full-text available
Antimicrobial peptides (AMPs) are promising pharmaceutical candidates for the prevention and treatment of infections caused by multidrug-resistant ESKAPE pathogens, which are responsible for the majority of hospital-acquired infections. Clinical translation of AMPs has been limited, in part by apparent toxicity on systemic dosing and by instability...
Article
Full-text available
Cellulose-based wound dressings are increasingly in demand due to their biocompatibility and extra-cellular matrix (ECM) mimicking properties. Although they contain no active constituents, pure cellulose-based scaffolds have promoted tissue regeneration. On the other hand, the absence of active ingredients opens the opportunity for the wound to bec...
Article
Innate defense regulators (IDRs) are synthetic host-defense peptides (HDPs) with broad-spectrum anti-infective properties, including immunomodulatory, anti-biofilm and direct antimicrobial activities. A lack of pharmacokinetic data about these peptides hinders their development and makes it challenging to fully understand how they work in vivo sinc...
Article
Full-text available
Engineered liposomes composed of the naturally occurring lipids sphingomyelin (Sm) and cholesterol (Ch) have been demonstrated to efficiently neutralize toxins secreted by Gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Here, we hypothesized that liposomes are capable of neutralizing cytolytic virulence factors se...
Article
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Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nano-biotechnological tools for dentistry. Here, different scaffolds were tested for use during the pulp revascularization process, including poly(vinyl alcohol)-PVA hydrogels or resins, collagen hydrogels and poly(vinyl alcohol) PVA/ Chitosan (...
Article
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The arrival of SARS-CoV-2 to Aotearoa/New Zealand in February 2020 triggered a massive response at multiple levels. Procurement and sustainability of medical supplies to hospitals and clinics during the then upcoming COVID-19 pandemic was one of the top priorities. Continuing access to new personal protective equipment (PPE) was not guaranteed; thu...
Article
As a natural material that is abundant, versatile, and sustainable, cellulose is an alternative that is expected to substitute non-renewable polymers. The physicochemical characteristics of natural cellulose are related to its isolation process that results in cellulose having a particular chain length, crystallinity, and number of inter and intram...
Preprint
Full-text available
Members of the bacterial genus Pseudomonas form mutualistic, commensal and pathogenic associations with diverse hosts. The prevalence of host association across the genus suggests that symbiosis may be a conserved ancestral trait and that distinct symbiotic lifestyles may be more recently evolved. Here we show that the ColR/S two-component system,...
Article
Host defense peptides (HDPs) have been the subject of great interest for the treatment of multidrug-resistant bacterial infections due to their multimodal activity and low induction of resistance. However, aggregation, toxicity, and short biological half-life have limited their applicability for clinical treatment. Many methods have been explored t...
Article
Trans-translation is a unique bacterial ribosome rescue system that plays important roles in the tolerance to environmental stresses. It is composed of an ssrA-encoded tmRNA and a protein SmpB. In this study, we examined the role of trans-translation in antibiotic tolerance in Klebsiella pneumoniae and explored whether the inhibition of this mechan...
Article
Full-text available
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that causes considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis. P. aeruginosa can adapt to surface growth by undergoing swarming motility, a rapid multicellular movement that occurs on viscous soft surfaces with amino ac...
Article
Full-text available
Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear ma...
Article
Full-text available
The very common condition of sinusitis is characterized by persistent inflammation of the nasal cavity, which contributes to chronic rhinosinusitis and morbidity of cystic fibrosis patients. Colonization by opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa triggers inflammation that is exacerbated by defects in the in...
Article
Due to the increasing inability of antibiotics to treat multidrug-resistant (MDR) bacteria, metal and metal oxide nanoparticles have been gaining interest as antimicrobial agents. Among those, silver nanoparticles have been used extensively as broad-spectrum antimicrobial agents. Here, we describe a newly-developed, 10-min (120 °C at 5 bar pressure...
Article
Antibiotic resistance in Gram-negative bacteria causes serious health issues worldwide. Bacteria employ several resistance mechanisms to cope with antimicrobials. One of their strategies is to reduce the permeability of antibiotics either through general diffusion porins or substrate-specific channels. In this study, one of the substrate-specific c...
Article
Swarming motility in Pseudomonas aeruginosa is a multicellular adaptation induced by semisolid medium with amino acids as a nitrogen source. By phenotypic screening, we differentiated swarming from other complex adaptive phenotypes, such as biofilm formation, swimming and twitching, by identifying a swarming-specific mutant in ptsP, a metabolic reg...
Article
Significance The host environment in which infection occurs plays a crucial role in the interaction between Pseudomonas aeruginosa and antibiotic treatments. To make up for the lack of new antibiotics, alternative approaches, such as combination therapy and discovery of novel activity of known antibiotics in the host environment, are vital for trea...
Article
Therapeutic options to treat multidrug resistant bacteria, especially when present in biofilms, are limited due to their high levels of antibiotic resistance. Here, we report the anti-biofilm and immunomodulatory activities of the host defense peptide (HDP)-mimicking β-peptide polymer (20:80 Bu:DM) and investigated its activity in vivo. The polymer...
Article
Full-text available
There is a critical need for more-effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing clinical drugs to be repurposed as antibiotics. We examined the mechanisms of action and basis of innate Gram-negative resistance for the anthelmintic dr...
Article
Host defence peptides have drawn significant attention as new drugs or drug adjuvants to combat multi-drug resistant bacteria. In this study, we report the development of cyclic derivatives of the immunomodulatory and anti-biofilm innate defence regulator peptide (IDR)-1018, based on three different synthetic strategies including head-to-tail cycli...
Article
Full-text available
Microorganisms need to adapt rapidly to survive harsh environmental changes. Here, we showed the broad influence of the highly studied bacterial stringent stress response under nonstressful conditions that indicate its general physiological importance and might reflect the readiness of bacteria to respond to and activate acute stress responses. Usi...
Article
Full-text available
Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membrane perforation and inoculatio...
Preprint
Full-text available
The bacterial stringent stress response, mediated by the signaling molecule guanosine tetra-phosphate, ppGpp, has recently gained attention as being important during normal cellular growth and as potential new therapeutic target, which warrants detailed mechanistic understanding. Here, we used intracellular protein tracking in Pseudomonas aeruginos...
Article
Full-text available
The emergence of multidrug-resistant Escherichia coli has become a great challenge in treating nosocomial infections. The polymyxin antibiotic colistin is used as a ‘last-line’ therapy for such strains, but resistance to colistin is increasingly emerging all over the world. In this study, we investigated lipopolysaccharides (LPS) of colistin-resist...
Article
Full-text available
Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of nosocomial and chronic infections contributing to morbidity and mortality in cystic fibrosis patients. One of the reasons for its success as a pathogen is its ability to adapt to a broad range of circumstances. Here, we show the involvement of the general nitrogen regulato...
Preprint
Full-text available
One avenue to combat multidrug-resistant Gram-negative bacteria is the co-administration of multiple drugs (combination therapy), which can be particularly promising if drugs synergize. The identification of synergistic drug combinations, however, is challenging. Detailed understanding of antibiotic mechanisms can address this issue by facilitating...
Article
Full-text available
Cystic fibrosis (CF) is a genetic disease that affects mucin-producing body organs such as the lungs. Characteristic of CF is the production of thick, viscous mucus, containing the glycoprotein mucin, that can lead to progressive airway obstruction. Recently, we demonstrated that the presence of mucin induced a rapid surface adaptation in motile ba...
Article
Bacterial biofilm formation on medical devices is a threat to healthcare systems worldwide as bacteria within a biofilm are more resistant to standard antimicrobial therapies. Herein, we introduce a nitroxide-based antibiofilm coating strategy, which is specifically designed to prevent biofilm formation of Gram-negative pathogens such as Pseudomona...
Article
Anti-biofilm peptides are a subset of antimicrobial peptides and represent promising broad-spectrum agents for the treatment of bacterial biofilms, though some display host toxicity in vivo. Here we evaluated nanogels composed of modified hyaluronic acid for the encapsulation of the anti-biofilm peptide DJK-5 in vivo. Nanogels of 174 to 194 nm enca...
Article
Full-text available
In the face of rising antimicrobial resistance, there is an urgent need for the development of efficient and effective anti‐infective compounds. Adaptive resistance, a reversible bacterial phenotype characterized by the ability to surmount antibiotic challenge without mutation, is triggered to cope in situ with several stressors and is very common...
Article
Antimicrobial peptides have been the focus of considerable research, however issues associated with toxicity and aggregation have the potential to limit clinical applications. Here, a derivative of a truncated version of aurein 2.2 (aurein 2.2Δ3), namely peptide 73, was investigated, along with its D-amino acid counterpart (D-73) and a retro-invers...
Article
Antimicrobial resistance is an increasing threat to human health because it reduces available treatment options for common infectious diseases, rendering them extremely dangerous and potentially fatal. Bacterial pathogens resistant to last resort antibiotics are on the rise and have spread all over the globe. Although antibiotics have been successf...
Data
Antibiotics used in this study. (DOCX)
Data
Outer membrane permeabilization by peptides, cf. antibiotics, at 10-fold higher than their corresponding MICs. The uptake of the fluorophore NPN in the presence of different antibiotics and synthetic peptides was determined by assessing increased fluorescence at an excitation wavelength of 350 nm and an emission wavelength of 420 nm due to partitio...
Data
Plasmids used in this study. (DOCX)
Data
Activity of tested antibiotics and peptides in vivo in the mouse abscess model. (DOCX)
Data
Influence of the stringent response on the combined efficacy of ciprofloxacin and peptides against P. aeruginosa LESB58 in vitro. The MIC values refer to the concentration required to give 100% inhibition of planktonic cell growth in MHB medium. Checkerboard titration experiments were performed to assess the synergistic interactions between DJK-5 o...
Data
Strains used in this study. (DOCX)
Article
Full-text available
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), typified by the pulse-field type USA300, is an emerging endemic pathogen that is spreading rapidly among healthy people. CA-MRSA causes skin and soft tissue infections, life-threatening necrotizing pneumonia and sepsis, and is remarkably resistant to many antibiotics. Here...
Article
The concept of Helicobacter pylori biofilm formation is relatively new. To help provide a foundation for future biofilm studies, we characterized the biofilm formation ability of a common H. pylori lab strain, G27. The goal of this study was to evaluate biofilm formation by G27 in response to common culture conditions and to explore the biofilm mat...
Chapter
Chronic wounds are a growing clinical concern worldwide with only a few treatment options available to address the fundamental causes of non-healing wounds. There is increasing evidence that the colonization of chronic wounds by bacteria growing within biofilms complicates treatment with conventional antibiotics and prevents proper wound healing. C...
Article
The conjugation of siderophores to antimicrobial molecules is an attractive strategy to overcome the low outer membrane permeability of Gram-negative bacteria. In this Trojan horse approach the transport of drug conjugates is redirected via TonB-dependent receptors (TBDR), involved in the uptake of essential nutrients including iron. Previous repor...
Article
Microbial biofilms, which are elaborate and highly resistant microbial aggregates formed on surfaces or medical devices, cause two-thirds of infections and constitute a serious threat to public health. Immunocompromised patients, individuals who require implanted devices, artificial limbs, organ transplants, or external life support and those with...
Article
Full-text available
Microorganisms continuously monitor their surroundings and adaptively respond to environmental cues. One way to cope with various stress-related situations is through the activation of the stringent stress response pathway. In Pseudomonas aeruginosa this pathway is controlled and coordinated by the activity of the RelA and SpoT enzymes that metabol...
Article
Biofilms represent an adaptive lifestyle where microbes grow as structured aggregates in many different environments, e.g. on body surfaces and medical devices. They are a profound threat in medical (and industrial) settings and cause two-thirds of all infections. Biofilm bacteria are especially recalcitrant to common antibiotic treatments, demonst...
Article
The OccK protein subfamily located in the outer membrane of Pseudomonas aeruginosa contains dynamic channels with several conformational states that range from open to closed forms. The molecular determinants of the OccK channels that contribute to the diverse gating has, however, remained elusive so far. Performing molecular dynamics simulations (...
Article
Full-text available
The outer membrane of Gram-negative bacteria presents an efficient barrier to the permeation of antimicrobial molecules. One strategy pursued to circumvent this obstacle is to hijack transport systems for essential nutrients such as iron. BAL30072 and MC-1 are two monobactams conjugated to a dihydroxypyridone siderophore that are active against Pse...
Article
Full-text available
The β-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum β-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the prese...
Article
Full-text available
Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacte...
Article
Synthesis of the exopolysaccharide levan occurs in the bacterial blight pathogen of soybean, Pseudomonas syringae pv. glycinea PG4180, when this bacterium encounters moderate to high concentrations of sucrose inside its host plant. The process is mediated by the temperature-dependent expression and secretion of two levansucrases, LscB and LscC. Pre...
Article
Full-text available
Here, we report the draft genome sequence of Dietzia maris , known previously as Rhodococcus maris . It is 3,505,372 bp in size with a G+C content of 73%. The draft genome sequence will improve our understanding of Dietzia maris related to other mycolata species and constitutes a basic tool for exploring the cell wall proteins.
Article
Full-text available
In the present study, we characterised the putative peptide ABC transporter SppABCD, which is co-transcribed with the TonB-dependent receptor SppR in Pseudomonas aeruginosa PA14. However, our data show that this transporter complex is not involved in the uptake of peptides. The fact that the TonB-dependent receptor SppR is regulated by an iron star...
Article
The treatment of bacterial diseases is facing twin threats with increasing bacterial antibiotic resistance and relatively few novel compounds or strategies under development or entering the clinic. Bacteria frequently grow on surfaces as biofilm communities encased in a polymeric matrix. The biofilm mode of growth is associated with 65-80% of all c...
Article
Several members of the ubiquitously found γ-proteobacterial genus Marinobacter were described or assumed to inhabit marine environments naturally enriched in heavy metals. However, direct studies that describe the ability of this genus to occupy such environments have not been conducted. To cope with heavy metal stress, bacteria possess specific ef...