Biology subjects

Maree, M.

Publications and source records attributed to Maree, M..

5 recordsLinked to original sources

bioRxiv2025

Barriers to Antimicrobial Resistance Gene Exchange in Methicillin Resistant Staphylococcus aureus Cluster into Transfer Islands

Horizontal gene transfer (HGT) via generalised transduction is a major driver of antimicrobial resistance (AMR) in Staphylococcus aureus, yet the genetic barriers regulating phage-mediated transfer remain poorly defined. Using a co-culture gene transfer rate assay (COGTRA) that quantifies phage-dependent resistance gene exchange under competitive, antibiotic-free conditions, we screened 1,920 mutants from the Nebraska Transposon Mutant Library for elevated transfer. We identified 32 validated high-transfer mutants that act as HGT barriers, 66% of which clustered within two chromosomal regions that we term S. aureus Transfer Islands (SauTI1 and SauTI2). SauTI loci restricted generalised transduction bidirectionally, and SauTI1 genes were widespread across S. aureus genomes yet showed lineage-specific variation. SauTI1 encodes an SMC2-Cbf1 condensin-nuclease module whose disruption markedly increases generalised transduction and plasmid transfer, resembling Wadjet-like restriction systems. Together, these findings identify clustered defence loci that restrict HGT in S. aureus and identify SauTIs as key regulators of AMR evolution.

genetics↗

bioRxiv2025

Targeting Aurora kinases as essential cell cycle regulators to deliver multi-stage antimalarials against Plasmodium falciparum

Kinases that play critical roles in the development and adaptation of Plasmodium falciparum present novel opportunities for chemotherapeutic intervention. Of particular interest are mitotic kinases that regulate the proliferation of the parasites by controlling nuclear division, segregation and cytokinesis. We evaluated the potential of human Aurora kinase (Aur) inhibitors to inhibit P. falciparum development by targeting members of the Aurora-related kinase (Ark) family in this parasite. Several human AurB inhibitors exhibited multistage potency (<250 nM) against all proliferative stages of parasite development, including asexual blood stages, liver schizonts and male gametes. Among the most potent compounds, hesperadin and AT83 exhibit >1000x selectivity towards the parasite without concerns about mammalian cell toxicity. Importantly, we identified PfArk1 as the principal vulnerable Ark family member, with specific inhibition of PfArk1 as the primary target for hesperadin and the human anaplastic lymphoma kinase (ALK) inhibitor TAE684. Hesperadins whole-cell and protein activity validates it as a unique PfArk1 tool compound. Inhibition of PfArk1 results in the parasites inability to complete mitotic processes, presenting with unsegregated, multi-lobed nuclei caused by aberrant microtubule organization. This suggests that PfArk1 is the main Aur mitotic kinase in proliferative stages of Plasmodium, characterized by bifunctional AurA and B activity. This paves the way for drug discovery campaigns based on hesperadin targeting PfArk1.

molecular biology↗

bioRxiv2023

SCCmec transformation requires living donor cells in mixed biofilms

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that has emerged through the horizontal acquisition of the staphylococcus cassette chromosome mec (SCCmec). Previously, we showed that SCCmec from heat-killed donors can be transferred via natural transformation in biofilms at frequencies of 10-8-10-7. Here, we show an improved transformation assay of SCCmec with frequencies up to 10-2 using co-cultured biofilms with living donor cells. The Ccr-attB system played an important role in SCCmec transfer, and the deletion of ccrAB recombinase genes reduced the frequency [~]30-fold. SCCmec could be transferred from either MRSA or methicillin-resistant coagulase-negative staphylococci to some of methicillin-sensitive S. aureus recipients. In addition, the transformation of other plasmid or chromosomal genes is enhanced by using living donor cells. This study emphasizes the role of natural transformation as an evolutionary ability of S. aureus and in MRSA emergence. ImportanceMethicillin-resistant Staphylococcus aureus (MRSA) stands out as the leading contributor to fatalities attributed to antibiotic-resistant infections. To comprehend its emergence and dissemination, it is crucial to understand the mechanisms behind it. MRSA has arisen through the horizontal acquisition of the methicillin resistance gene mecA, which is harboured within the staphylococcal cassette chromosome (SCCmec). Our study sheds light on a noteworthy discovery: when methicillin-sensitive S. aureus recipient cells are grown alongside viable methicillin-resistant donor cells in co-cultured biofilms, a highly efficient transfer of SCCmec occurs, both within the same species and between different species. This remarkable transfer process is facilitated by natural transformation, underscoring its pivotal role in the evolution of staphylococci and the emergence of MRSA.

microbiology↗

bioRxiv2020

Novel multicellular prokaryote discovered next to an underground stream

The emergence of multicellularity is a key event in the evolution of life and is an attractive challenge among researchers, including those investigating the artificial design of cellular behavior1. Multicellular organisms are widely distributed on Earth, and retracing the specific conditions conducive for the initial transition from unicellularity to multicellularity is difficult. However, by examining organisms that inhabit unique (e.g., isolated) environmental niches, we may be able to get a glimpse into primitive multicellularity in the context of a given environment. Here we report the discovery of a new bacterium that displayed multicellular-like characteristics and behavior. The bacterium, which was isolated adjacent to an underground stream in a limestone cave, is to be named Jeongeupia sacculi sp. nov. HS-3. On a solid surface, HS-3 self-organizes its filamentous cells to form an appearance similar to the nematic phase of a liquid crystal2. Mature colonies produce and accommodate clusters of coccobacillus progeny, and release them upon contact with water. HS-3 demonstrated novel, spatiotemporally regulated multicellularity that can resolve the so-called competition-dispersal trade-off problem3. This study illustrates a hypothetical missing link on the emergence of multicellularity.

evolutionary biology↗

bioRxiv2020

MRSA emerges through natural transformation

Methicillin-resistant Staphylococcus aureus (MRSA) carries the resistance gene mecA in the staphylococcal cassette chromosome (SCC) that disseminates among staphylococci but the cell-to-cell transmission mechanism of SCC has not been clarified for half a century1. Here, we present evidence for efficient natural transformation in Staphylococcus aureus and its relevance in SCCmec transmission. We found that growth in biofilm conditions increased the transformation efficiency in a dependent manner on two component signal transduction systems, TCS13 (AgrCA) and TCS17 (BraSR). Strikingly, we demonstrate that natural transformation mediates the transfer of SCCmec from MRSA or methicillin-resistant coagulase negative staphylococci to methicillin-sensitive S. aureus. The site-specific insertion/excision system mediated by cassette chromosome recombinases was essential for SCCmec transformation while the stability of SCCmec varied depending on SCC types and recipients. We propose that natural transformation is the key process in the emergence of MRSA.

microbiology↗