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Transcriptomic insights into the virulence of Acinetobacter baumannii during infection-role of iron uptake and siderophore production genes

Ten KE, Rahman S, Tan HS

FEBS Lett, 2025 Jan;599(1):120-139.
PMID: 39572900 DOI: 10.1002/1873-3468.15061

Acinetobacter baumannii, a top-priority WHO pathogen, causes life-threatening infections in immunocompromised patients, leading to prolonged hospitalisation and high mortality. Here, we used the Galleria mellonella model to investigate community strain C98 (Ab-C98) virulence via transcriptomic analysis. Ab-C98 showed greater killing and faster colonisation in larvae than the clinical reference strain (ATCC BAA1605). Genes in three iron clusters, acinetobactin, baumannoferrin and the Feo system, were significantly up-regulated. Targeted knockout of siderophore genes (basC, bfnD, and the gene encoding isochorismatase) significantly increased the survival of infected larvae by at least 35.16%, identifying these genes as potential targets for developing anti-virulence agents against A. baumannii.
Fulltext Uncovering the transcriptome-wide RNA modifications in Acinetobacter baumannii

Ten KE, Rahman S, Tan HS

Microb Genom, 2024 Nov;10(11).
PMID: 39565092 DOI: 10.1099/mgen.0.001327

Despite being a major human pathogen, limited studies have reported RNA modifications in Acinetobacter baumannii. These post-transcriptional modifications play crucial regulatory roles in bacteria and have also been shown to modulate bacterial virulence. Using nanopore sequencing, we characterized RNA modifications in a virulent A. baumannii strain (Ab-C98) under free-living (mid-exponential phase in vitro culture) and during an early stage of infection (3 h post-infection) in Galleria mellonella larvae. Analysis revealed that m5C methylations are essential for ribosome synthesis, while m6A and Ψ are involved in metabolic pathways and translation processes. Iron-chelating genes exbD (m5C and m6A) and feoB (m6A and Ψ) and RNA polymerase subunit rpoC (m6A and Ψ) were selectively modified during infection. This first transcriptome-wide study highlights the potential regulatory roles of m5C, m6A and Ψ modifications in A. baumannii during infection.
Fulltext Characterization of multidrug-resistant Acinetobacter baumannii strain ATCC BAA1605 using whole-genome sequencing

Ten KE, Md Zoqratt MZH, Ayub Q, Tan HS

BMC Res Notes, 2021 Mar 04;14(1):83.
PMID: 33663564 DOI: 10.1186/s13104-021-05493-z

OBJECTIVE: The nosocomial pathogen, Acinetobacter baumannii, has acquired clinical significance due to its ability to persist in hospital settings and survive antibiotic treatment, which eventually resulted in the rapid spread of this bacterium with antimicrobial resistance (AMR) phenotypes. This study used a multidrug-resistant A. baumannii (strain ATCC BAA1605) as a model to study the genomic features of this pathogen.
RESULTS: One circular chromosome and one circular plasmid were discovered in the complete genome of A. baumannii ATCC BAA1605 using whole-genome sequencing. The chromosome is 4,039,171 bp long with a GC content of 39.24%. Many AMR genes, which confer resistance to major classes of antibiotics (beta-lactams, aminoglycosides, tetracycline, sulphonamides), were found on the chromosome. Two genomic islands were predicted on the chromosome, one of which (Genomic Island 1) contains a cluster of AMR genes and mobile elements, suggesting the possibility of horizontal gene transfer. A subtype I-F CRISPR-Cas system was also identified on the chromosome of A. baumannii ATCC BAA1605. This study provides valuable genome data that can be used as a reference for future studies on A. baumannii. The genome of A. baumannii ATCC BAA1605 has been deposited at GenBank under accession no. CP058625 and CP058626.
Fulltext Use of the waxworm Galleria mellonella larvae as an infection model to study Acinetobacter baumannii

Ten KE, Muzahid NH, Rahman S, Tan HS

PLoS One, 2023;18(4):e0283960.
PMID: 37018343 DOI: 10.1371/journal.pone.0283960

Galleria mellonella larvae have been increasingly used in research, including microbial infection studies. They act as suitable preliminary infection models to study host-pathogen interactions due to their advantages, such as the ability to survive at 37°C mimicking human body temperature, their immune system shares similarities with mammalian immune systems, and their short life cycle allowing large-scale studies. Here, we present a protocol for simple rearing and maintenance of G. mellonella without requiring special instruments and specialized training. This allows the continuous supply of healthy G. mellonella for research purposes. Besides, this protocol also provides detailed procedures on the (i) G. mellonella infection assays (killing assay and bacterial burden assay) for virulence studies and (ii) bacterial cell harvesting from infected larvae and RNA extraction for bacterial gene expression studies during infection. Our protocol could not only be used in the studies of A. baumannii virulence but can also be modified according to different bacterial strains.
Fulltext Genomic and phenotypic characterization of Acinetobacter colistiniresistens isolated from the feces of a healthy member of the community

Muzahid NH, Md Zoqratt MZH, Ten KE, Hussain MH, Su TT, Ayub Q, et al.

Sci Rep, 2023 Aug 03;13(1):12596.
PMID: 37537198 DOI: 10.1038/s41598-023-39642-0

Acinetobacter species are widely known opportunistic pathogens causing severe community and healthcare-associated infections. One such emerging pathogen, Acinetobacter colistiniresistens, is known to exhibit intrinsic resistance to colistin. We investigated the molecular characteristics of A. colistiniresistens strain C-214, isolated from the fecal sample of a healthy community member, as part of a cohort study being conducted in Segamat, Malaysia. Comparison of the whole genome sequence of C-214 with other A. colistiniresistens sequences retrieved from the NCBI database showed 95% sequence identity or more with many of the genome sequences representing that species. Use of the Galleria mellonella killing assay showed that C-214 was pathogenic in this model infection system. The strain C-214 had a colistin and polymyxin B MIC of 32 and 16 mg/L, respectively. Besides, it was resistant to cefotaxime, amikacin, and tetracycline and showed moderate biofilm-producing ability. Different genes associated with virulence or resistance to major classes of antibiotics were detected. We observed mutations in lpxA/C/D in C-214 and other A. colistiniresistens strains as probable causes of colistin resistance, but the biological effects of these mutations require further investigation. This study provides genomic insights into A. colistiniresistens, a potentially pathogenic bacterium isolated from a community member and notes the public health threat it may pose.