Publications by authors named "Xin-Ee Tan"
A Comprehensive Review on Phage Therapy and Phage-Based Drug Development.
Antibiotics (Basel)
September 2024
Article Synopsis
- Phage therapy is gaining attention as a potential solution for treating infections caused by multidrug-resistant bacteria, leveraging naturally occurring viruses called bacteriophages.
- The review covers the historical background, recent advancements, and various applications of phages, including their use in medical fields like vaccine development and cancer treatment.
- Despite its advantages, phage therapy still faces obstacles such as maintaining phage stability, dealing with immune responses, and navigating regulatory challenges for approval.
Article Synopsis
- The study presents a new phagemid-based system that produces CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) specifically targeting multidrug-resistant Staphylococcus aureus.
- By optimizing phagemid copy numbers, researchers achieved higher yields and purity of AB-capsids, illustrating a direct relationship between phagemid quantity and capsid production.
- The developed AB-capsids effectively eliminate targeted S. aureus strains while leaving non-target strains unharmed, showcasing their potential as effective tools against antibiotic-resistant bacteria.
Article Synopsis
- The lab created a phagemid system to generate CRISPR-Cas13a-antimicrobial capsids specifically targeting MRSA to combat rising antimicrobial resistance.
- They faced a challenge with unwanted wild-type phage production during packaging, which was addressed by introducing silent mutations to reduce contamination while maintaining efficiency.
- The optimized system showed effective sequence-specific killing of MRSA strains but highlights the need for further research on its effectiveness against other bacteria and in real body conditions.
Article Synopsis
- The study focuses on oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA), which poses new treatment challenges due to its ability to develop resistance through chromosomal mutations.
- Researchers analyzed six mutant strains with decreased oxacillin susceptibility, examining how mutations in RNA polymerase (RNAP) genes led to transcription dysfunction and an accumulation of certain metabolites.
- The findings indicated that these mutations resulted in cell wall thickening, which ultimately decreased the mutants' susceptibility to β-lactam antibiotics, highlighting the need for a better understanding of these mechanisms for effective clinical management.
RNA and single-stranded DNA (ssDNA) phages make up an understudied subset of bacteriophages that have been rapidly expanding in the last decade thanks to advancements in metaviromics. Since their discovery, applications of genetic engineering to ssDNA and RNA phages have revealed their immense potential for diverse applications in healthcare and biotechnology. In this review, we explore the past and present applications of this underexplored group of phages, particularly their current usage as therapeutic agents against multidrug-resistant bacteria.
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- Non-menstrual toxic shock syndrome (non-mTSS) is a severe illness linked to superantigen-producing strains such as those that produce TSST-1, but the rarity of TSS cases remains largely unexplained.
- Researchers measured TSST-1 production in 541 clinical isolates, comparing strains from non-mTSS patients with those from other conditions, and investigated the role of specific mutations in the promoter affecting TSST-1 inducibility by human serum.
- Results indicated that a small percentage of clinical isolates produced more TSST-1 in the presence of serum, particularly in non-mTSS strains from clonal complex (CC)-5, with certain genetic variations in the promoter implicated in this serum-induced induction.
The bacteriophage (or phage for short) has been used as an antibacterial agent for over a century but was abandoned in most countries after the discovery and broad use of antibiotics. The worldwide emergence and high prevalence of antimicrobial-resistant (AMR) bacteria have led to a revival of interest in the long-forgotten antibacterial therapy with phages (phage therapy) as an alternative approach to combatting AMR bacteria. The rapid progress recently made in molecular biology and genetic engineering has accelerated the generation of phage-related products with superior therapeutic potentials against bacterial infection.
View Article and Find Full Text PDFStaphylococcus aureus strains that are susceptible to the β-lactam antibiotic oxacillin despite carrying mecA (OS-MRSA) cause serious clinical problems globally because of their ability to easily acquire β-lactam resistance. Understanding the genetic mechanism(s) of acquisition of the resistance is therefore crucial for infection control management. For this purpose, a whole-genome sequencing-based analysis was performed using 43 clinical OS-MRSA strains and 100 mutants with reduced susceptibility to oxacillin (MICs 1.
View Article and Find Full Text PDFWe first reported a phenomenon of cross-resistance to vancomycin (VCM) and daptomycin (DAP) in methicillin-resistant Staphylococcus aureus (MRSA) in 2006, but mechanisms underlying the cross-resistance remain incompletely understood. Here, we present a follow-up study aimed to investigate genetic determinants associated with the cross-resistance. Using 12 sets of paired DAP susceptible (DAP) and DAP non-susceptible (DAP) MRSA isolates from 12 patients who had DAP therapy, we (i) assessed susceptibility to DAP and VCM, (ii) compared whole-genome sequences, (iii) identified mutations associated with cross-resistance to DAP and VCM, and (iv) investigated the impact of altered gene expression and metabolic pathway relevant to the cross-resistance.
View Article and Find Full Text PDFThe emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. Here we report the development of a series of CRISPR-Cas13a-based antibacterial nucleocapsids, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus by recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs are generated by packaging programmed CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes.
View Article and Find Full Text PDFComplete Genome Sequence of a Panton-Valentine Leukocidin-Negative Staphylococcus aureus Strain Isolated from a Patient with Pervasive Necrotizing Soft Tissue Infection.
Microbiol Resour Announc
June 2020
Article Synopsis
- The role of Panton-Valentine leukocidin (PVL) toxin in necrotizing soft tissue infections (NSTI) remains debated among researchers.
- This study presents the complete genome sequence of a PVL-negative strain, identified as JMUB1273.
- The strain was obtained from a patient suffering from severe NSTI, highlighting the complexity of these infections.
Article Synopsis
- The text mentions a correction related to a previous article published with the DOI: 10.3389/fmicb.2019.02838.!
- It indicates that there may have been errors or updates that needed to be addressed in the original article.!
- The correction aims to clarify information and ensure the accuracy of the published research within the field of microbiology.!
Article Synopsis
- CRISPR-Cas13a, an RNA-targeting system, exhibits unique cleavage activities for single-stranded RNA and was studied through whole genome sequences of 11 strains compared to 18 others to analyze its diversity and occurrence.
- The research found a wide distribution of various CRISPR-Cas types among the genomes, with notable absence in 20.5% of strains, and highlighted the highly divergent nature of Cas13a effectors, yet their ability to impede bacterial growth remained consistent.
- Analysis of CRISPR spacers revealed significant diversity, with only 4.4% shared between strains, while the organization and prevalence of different CRISPR-Cas types underscored the evolutionary relationships and characteristics of these
Pulsed-field gel electrophoresis (PFGE) is considered the "gold standard" for bacteria typing. The method involves enzyme restriction of bacteria DNA, separation of the restricted DNA bands using a pulsed-field electrophoresis chamber, followed by clonal assignment of bacteria based on PFGE banding patterns. Various PFGE protocols have been developed for typing different bacteria, leading it to be one of the most widely used methods for phylogenetic studies, food safety surveillance, infection control and outbreak investigations.
View Article and Find Full Text PDFIn this study, vancomycin-intermediate (VISA) cells carrying and (or) mutations were shown to be more resistant to oxidative stress. infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appear to be physiological adaptations associated with the VISA phenotype in the Mu50 lineage.
View Article and Find Full Text PDFSevere community-acquired pneumonia (CAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare and is usually associated with rapid progression to death. Here, we report the complete genome sequence of the MRSA strain JMUB3031, which was isolated from a patient with fatal CAP.
View Article and Find Full Text PDFBackground: Staphylococcus caprae is an animal-associated bacterium regarded as part of goats' microflora. Recently, S. caprae has been reported to cause human nosocomial infections such as bacteremia and bone and joint infections.
View Article and Find Full Text PDFComparative proteomic profiling between 2 vancomycin-intermediate Staphylococcus aureus (VISA) strains, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm, and vancomycin-susceptible S. aureus (VSSA) strain Mu50Ω revealed upregulated levels of catabolic ornithine carbamoyltransferase (ArcB) of the arginine catabolism pathway in VISA strains. Subsequent analyses showed that the VISA strains have higher levels of cellular ATP and ammonia, which are by-products of arginine catabolism, and displayed thicker cell walls.
View Article and Find Full Text PDFThe annual prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia has been estimated to be 30 % to 40 % of all S. aureus infections. Nevertheless, data on the antimicrobial resistance and genetic diversity of Malaysian MRSAs remain few.
View Article and Find Full Text PDFObjective: To genotypically characterize methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from medical and surgical wards in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in 2009.
Methods: MRSA strains were collected and molecularly typed by pulsed-field gel electrophoresis (PFGE).
Results: PFGE typing on 180 MRSA isolated in UKMMC identified 5 pulsotypes (A-E) and 6 singletons, where pulsotypes B and C were suspected to be divergent clones originating from a single ancestor.
Draft Genome Sequences of Four Nosocomial Methicillin-Resistant Staphylococcus aureus (MRSA) Strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) Representative of Dominant MRSA Pulsotypes Circulating in a Malaysian University Teaching Hospital.
Genome Announc
January 2013
Here, we report the draft genome sequences of four nosocomial methicillin-resistant Staphylococcus aureus strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) isolated from a university teaching hospital in Malaysia. Three of the strains belong to sequence type 239 (ST239), which has been associated with sustained hospital epidemics worldwide.
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