Research

Cain AK

• Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IP_3-4K March 31, 2025
  New antifungals are urgently needed to treat deadly fungal infections. Targeting the fungal inositol polyphosphate kinases IP(3-4)K (Arg1) and IP(6)K (Kcs1) is a promising strategy as it has been validated genetically to be crucial for fungal virulence but never pharmacologically. We now report the synthesis of DT-23, an analogue of N2-(m-trifluorobenzylamino)-N6-(p-nitrobenzylamino)purine (TNP), and demonstrate that […]
  Desmarini Desmarini
• High-throughput transposon mutagenesis in the family Enterobacteriaceae reveals core essential genes and rapid turnover of essentiality August 29, 2024
  The Enterobacteriaceae are a scientifically and medically important clade of bacteria, containing the model organism Escherichia coli, as well as major human pathogens including Salmonella enterica and Klebsiella pneumoniae. Essential gene sets have been determined for several members of the Enterobacteriaceae, with the Keio E. coli single-gene deletion library often regarded as a gold standard. […]
  Fatemeh A Ghomi
• A synthetic peptide mimic kills Candida albicans and synergistically prevents infection August 9, 2024
  More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited. Here we investigate the antifungal mode […]
  Sebastian Schaefer
• Spectrum of activity and mechanisms of azole-bisphosphonate synergy in pathogenic <em>Candida</em> May 2, 2024
  Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common Candida species implicated in human disease is Candida albicans, but other species like Candida glabrata are emerging. The use of azole antifungals for treatment is limited by increasing […]
  Aidan Kane
• High-precision screening and sorting of double emulsion droplets April 18, 2024
  Mounting evidence suggests that cell populations are extremely heterogeneous, with individual cells fulfilling different roles within the population. Flow cytometry (FC) is a high-throughput tool for single-cell analysis that works at high optical resolution. Sub-populations with unique properties can be screened, isolated and sorted through fluorescence-activated cell sorting (FACS), using intracellular fluorescent products or surface-tagged […]
  Siyuan Zhuang
• Transposons Carrying the <em>aacC2e</em> Aminoglycoside and <em>bla</em>_TEM Beta-Lactam Resistance Genes in <em>Acinetobacter</em> April 9, 2024
  This study examines the genetic contexts and evolutionary steps responsible for the formation of the widely spread transposon Tn6925 carrying bla(TEM) and aacC2e, which confers resistance to beta-lactam and aminoglycoside antibiotics in Gram-negative bacteria. The bla(TEM-1) and aacC2e genes were found in several transposons. They were first observed within an IS26 bounded 3.7 kb transposon […]
  Liam A Tobin
• The 3' UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions April 7, 2024
  Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S. aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using […]
  Daniel G Mediati
• A method to correct for local alterations in DNA copy number that bias functional genomics assays applied to antibiotic-treated bacteria March 12, 2024
  Functional genomics techniques, such as transposon insertion sequencing and RNA-sequencing, are key to studying relative differences in bacterial mutant fitness or gene expression under selective conditions. However, certain stress conditions, mutations, or antibiotics can directly interfere with DNA synthesis, resulting in systematic changes in local DNA copy numbers along the chromosome. This can lead to […]
  Geraldine J Sullivan
• Systematic analyses identify modes of action of ten clinically relevant biocides and antibiotic antagonism in Acinetobacter baumannii October 9, 2023
  Concerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic […]
  Liping Li
• The Antimicrobial Properties of Pd^II - and Ru^II -pyta Complexes August 18, 2023
  Infections associated with antimicrobial resistance (AMR) are poised to become the leading cause of death in the next few decades, a scenario that can be ascribed to two phenomena: antibiotic over-prescription and a lack of antibiotic drug development. The crowd-sourced initiative Community for Open Antimicrobial Drug Discovery (CO-ADD) has been testing research compounds contributed by […]
  Annick van Niekerk
• Portrait of a killer: Uncovering resistance mechanisms and global spread of Acinetobacter baumannii August 10, 2023
  Antibiotic resistance is a growing global concern in the field of medicine as it renders bacterial infections difficult to treat and often more severe. Acinetobacter baumannii is a gram-negative bacterial pathogen causing a wide range of infections, including pneumonia, sepsis, urinary tract infections, and wound infections. A. baumannii has emerged as a significant healthcare-associated pathogen […]
  Amy K Cain
• A global data-driven census of <em>Salmonella</em> small proteins and their potential functions in bacterial virulence May 24, 2023
  Small proteins are an emerging class of gene products with diverse roles in bacterial physiology. However, a full understanding of their importance has been hampered by insufficient genome annotations and a lack of comprehensive characterization in microbes other than Escherichia coli. We have taken an integrative approach to accelerate the discovery of small proteins and […]
  Elisa Venturini
• The evolutionary tale of eight novel plasmids in a colistin-resistant environmental <em>Acinetobacter baumannii</em> isolate May 12, 2023
  Acinetobacter baumannii is an important opportunistic pathogen known for its high levels of resistance to many antibiotics, particularly those considered last resorts such as colistin and carbapenems. Plasmids of this organism are increasingly associated with the spread of clinically important antibiotic resistance genes. Although A. baumannii is a ubiquitous organism, to date, most of the […]
  Farzana T Prity
• DksA is a conserved master regulator of stress response in Acinetobacter baumannii May 9, 2023
  Coordination of bacterial stress response mechanisms is critical for long-term survival in harsh environments for successful host infection. The general and specific stress responses of well-studied Gram-negative pathogens like Escherichia coli are controlled by alternative sigma factors, archetypically RpoS. The deadly hospital pathogen Acinetobacter baumannii is notoriously resistant to environmental stresses, yet it lacks RpoS, […]
  Ram P Maharjan
• Cross-protection and cross-feeding between Klebsiella pneumoniae and Acinetobacter baumannii promotes their co-existence February 9, 2023
  Acinetobacter baumannii and Klebsiella pneumoniae are opportunistic pathogens frequently co-isolated from polymicrobial infections. The infections where these pathogens co-exist can be more severe and recalcitrant to therapy than infections caused by either species alone, however there is a lack of knowledge on their potential synergistic interactions. In this study we characterise the genomes of A. […]
  Lucie Semenec
• Microfluidic Separation and Enrichment of <em>Escherichia coli</em> by Size Using Viscoelastic Flows January 19, 2023
  Here, we achieve the separation and enrichment of Escherichia coli clusters from its singlets in a viscoelastic microfluidic device. E. coli, an important prokaryotic model organism and a widely used microbial factory, can aggregate in clusters, leading to biofilm development that can be detrimental to human health and industrial processes. The ability to obtain high-purity […]
  Tianlong Zhang
• Identification of a Novel LysR Family Transcriptional Regulator Controlling Acquisition of Sulfur Sources in Acinetobacter baumannii January 10, 2023
  l-cysteine biosynthesis from inorganic sulfur represents a major mechanism by which reduced sulfur is incorporated into organic compounds. Cysteine biosynthesis and regulation is well characterized in Escherichia coli. However, the regulation of sulfur metabolism in Acinetobacter baumannii is only partly understood, with the LysR-type regulator, GigC known to control some aspects of sulfur reduction. In […]
  Alaska Pokhrel
• Breaching the Barrier: Genome-Wide Investigation into the Role of a Primary Amine in Promoting E. coli Outer-Membrane Passage and Growth Inhibition by Ampicillin November 21, 2022
  Gram-negative bacteria are problematic for antibiotic development due to the low permeability of their cell envelopes. To rationally design new antibiotics capable of breaching this barrier, more information is required about the specific components of the cell envelope that prevent the passage of compounds with different physiochemical properties. Ampicillin and benzylpenicillin are β-lactam antibiotics with […]
  Claire Maher
• Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First <em>In Vivo</em> Experiments October 31, 2022
  There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so […]
  Angelo Frei
• Shape-based separation of drug-treated <em>Escherichia coli</em> using viscoelastic microfluidics June 1, 2022
  Here, we achieve shape-based separation of drug-treated Escherichia coli (E. coli) by viscoelastic microfluidics. Since shape is critical for modulating biological functions of E. coli, the ability to prepare homogeneous E. coli populations adopting uniform shape or sort bacterial sub-population based on their shape has significant implications for a broad range of biological, biomedical and […]
  Tianlong Zhang