Dr Varsha Naidu
Post Doctoral Researcher
School of Environmental and Life Sciences
Career Summary
Biography
Biography
Dr. Varsha Naidu earned her PhD from Macquarie University in 2021, with the Vice-chancellor’s Commendation for Academic Excellence under the guidance of Distinguished Professor Ian Paulsen. Her doctoral work delved into the molecular adaptations of a highly drug resistant hospital pathogen, Acinetobacter baumannii, and the role of multidrug efflux transport systems in pathogenic bacteria. Currently, as a Postdoctoral Fellow at the School of Environmental and Life Sciences in Associate Professor Karl Hassan’s lab, her research focusses on integrating functional and comparative genomics with molecular biology, protein engineering and biochemistry.
Research focus
Varsha’s research interest delves deep into three distinct focal areas. These include (1) identifying novel enzymes that play a crucial role in the catabolism of persistent pollutants, such as polycyclic aromatic hydrocarbons (PAHs), in the metabolically affluent Rhodococcus species for bioremediation purposes; (2) utilising coevolutionary methods to engineer membrane-embedded transport proteins for industrial applications and to decipher the evolutionary trajectory of these proteins (3) investigating molecular adaptations of antimicrobial resistant Acinetobacter baumannii, which has led to its success in a nosocomial environment.
Expertise for collaboration
- Computational biology - phylogenetics, multiomics, WGCNA, systems biology and highly experienced in transcriptomics data analysis
- Protein Chemistry - engineering, purification, characterisation and proteomics
- Molecular Biology - genetic manipulation (cloning, KOs and nucleic acid extractions)
- Other - Transposon Directed Insertion Site (TraDIS) sequencing, Electron Microscopy (TEM & SEM) and radioligand assays
Qualifications
- Master of Research, Macquarie University
Keywords
- Antimicrobial Resistance
- Functional Genomics
- Microbial Genomics
- Molecular Microbiology
- Multidrug Transporters
- Pathogens
Fields of Research
Code | Description | Percentage |
---|---|---|
310299 | Bioinformatics and computational biology not elsewhere classified | 30 |
310704 | Microbial genetics | 40 |
310199 | Biochemistry and cell biology not elsewhere classified | 30 |
Professional Experience
UON Appointment
Title | Organisation / Department |
---|---|
Post Doctoral Researcher | University of Newcastle School of Environmental and Life Sciences Australia |
Academic appointment
Dates | Title | Organisation / Department |
---|---|---|
1/3/2018 - 1/4/2018 | Visiting Research Scholar | University of Oslo Norway |
Professional appointment
Dates | Title | Organisation / Department |
---|---|---|
1/3/2021 - 1/9/2021 | BioCyc Curator | SRI International (Macquarie University node) Australia |
Awards
Award
Year | Award |
---|---|
2021 |
Vice-chancellor’s Commendation for Academic Excellence Macquarie University |
2019 |
NSW-ACT Nancy Millis Finalist Australian Society for Microbiology |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (12 outputs)
Year | Citation | Altmetrics | Link | ||||||||
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2023 |
Li L, Short FL, Hassan KA, Naidu V, Pokhrel A, Nagy SS, et al., 'Systematic analyses identify modes of action of ten clinically relevant biocides and antibiotic antagonism in
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2023 |
Naidu V, Shah B, Maher C, Paulsen IT, Hassan KA, 'AadT, a new weapon in
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2023 |
Naidu V, Bartczak A, Brzoska AJ, Lewis P, Eijkelkamp BA, Paulsen IT, et al., 'Evolution of RND efflux pumps in the development of a successful pathogen', Drug Resistance Updates, 66 (2023) [C1] Aims: This study examined the origins and evolution of the AdeABC, AdeFGH and AdeIJK efflux pumps in the Acinetobacter genus, including human and animal pathogens and species from... [more] Aims: This study examined the origins and evolution of the AdeABC, AdeFGH and AdeIJK efflux pumps in the Acinetobacter genus, including human and animal pathogens and species from non-clinical environments. Methods: Comparative genome analyses were performed using the reference sequences for 70 Acinetobacter species to identify putative orthologs of AdeABC, AdeFGH and AdeIJK and their regulators. Sequence similarities and the genomic locations of coding sequences were correlated with phylogeny to infer modes of evolution. Intraspecies variation was assessed in species of interest using up to 236 complete genome sequences. Mutants overproducing adeIJK in A. baylyi were examined to identify regulators of this system in a non A. baumannii species. Results: The results indicate that adeIJK has been a stable part of Acinetobacter genomes since the genesis of this genus, whereas adeABC and adeFGH were carried by less than half of the species, but showed some lineage specificity. The organisation and local genetic contexts of adeABC loci were particularly variable to the sub-species level, suggesting frequent recombination. Cognate regulatory systems were almost always found in the genomes of species encoding pumps. Mutations in adeN, which encodes a repressor of adeIJK, were selected by antibiotic exposure in A. baylyi, similar to previous findings in pathogenic lineages. Conclusions: The multidrug efflux capacity of clinical Acinetobacter strains stems from accessory and core genetic features. AdeIJK is likely to have ancient core function(s) that have promoted its maintenance, whereas recent antibiotic use may be driving the evolution of the AdeABC pump.
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2021 |
Naidu V, Shah B, Kamath KS, Chien A, Nagy S, Pokhrel A, et al., 'Identification of a novel ciprofloxacin tolerance gene, aciT, which contributes to filamentation in acinetobacter baumannii', Antimicrobial Agents and Chemotherapy, 65 (2021) [C1] Fluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important o... [more] Fluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms, including Acinetobacter baumannii. We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to subinhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analyses found that the most highly expressed genes and proteins were components of the intact prophage phiOXA. The next most highly expressed gene (and its protein product) under ciprofloxacin stress was a hypothetical gene, ABUW_0098, named here the Acinetobacter ciprofloxacin tolerance (aciT) gene. Disruption of this gene resulted in higher susceptibility to ciprofloxacin, and complementation of the mutant with a cloned aciT gene restored ciprofloxacin tolerance to parental strain levels. Microscopy studies revealed that aciT is essential for filamentation during ciprofloxacin stress in A. baumannii. Sequence analysis of aciT indicates the encoded protein is likely to be localized to the cell membrane. Orthologs of aciT are found widely in the genomes of species from the Moraxellaceae family and are well conserved in Acinetobacter species, suggesting an important role. With these findings taken together, this study has identified a new gene conferring tolerance to ciprofloxacin, likely by enabling filamentation in response to the antibiotic.
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2021 |
Zang M, Macdermott-Opeskin H, Adams FG, Naidu V, Waters JK, Carey AB, et al., 'The membrane composition defines the spatial organization and function of a major acinetobacter baumannii drug efflux system', mBio, 12 (2021) [C1] Acinetobacter baumannii is one of the world¿s most problematic nosoco-mial pathogens. The combination of its intrinsic resistance and ability to acquire resistance markers allow t... [more] Acinetobacter baumannii is one of the world¿s most problematic nosoco-mial pathogens. The combination of its intrinsic resistance and ability to acquire resistance markers allow this organism to adjust to antibiotic treatment. Despite being the primary barrier against antibiotic stress, our understanding of the A. baumannii membrane composition and its impact on resistance remains limited. In this study, we explored how the incorporation of host-derived polyunsaturated fatty acids (PUFAs) is associated with increased antibiotic susceptibility. Functional analyses of primary A. baumannii efflux systems indicated that AdeB-mediated antibiotic resistance was impacted by PUFA treatment. Molecular dynamics simulations of AdeB identified a specific morphological disruption of AdeB when positioned in the PUFA-enriched membrane. Collectively, we have shown that PUFAs can impact antibiotic efficacy via a vital relationship with antibiotic efflux pumps. Furthermore, this work has revealed that A. baumannii¿s unconditional desire for fatty acids may present a possible weakness in its multidrug resistance capacity. IMPORTANCE Antimicrobial resistance is an emerging global health crisis. Consequently, we have a critical need to prolong our current arsenal of antibiotics, in addition to the development of novel treatment options. Due to their relatively high abundance at the host-pathogen interface, PUFAs and other fatty acid species not commonly synthesized by A. baumannii maybeactivelyacquiredbyA. bau-mannii during infection and change the biophysical properties of the membrane beyond that studied in standard laboratory culturing media. Our work illustrates how the membrane phospholipid composition impacts membrane protein function, which includes an important multidrug efflux system in extensively-drug-resistant A. baumannii. This work emphasizes the need to consider including host-derived fatty acids in in vitro analyses of A. baumannii. Onabroaderscope, this study presents new findings on the potential health benefits of PUFA in indi-viduals at risk of contracting A. baumannii infections or those undergoing antibiotic treatment.
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2021 |
Short FL, Liu Q, Shah B, Clift HE, Naidu V, Li L, et al., 'The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump', Communications Biology, 4 (2021) [C1] Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control. Multidrug efflux pump... [more] Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control. Multidrug efflux pumps often transport metabolites, signals and host-derived molecules in addition to antibiotics or biocides. Understanding their ancestral physiological roles could inform the development of strategies to subvert their activity. In this study, we investigated the response of Acinetobacter baumannii to polyamines, a widespread, abundant class of amino acid-derived metabolites, which led us to identify long-chain polyamines as natural substrates of the disinfectant efflux pump AmvA. Loss of amvA dramatically reduced tolerance to long-chain polyamines, and these molecules induce expression of amvA through binding to its cognate regulator AmvR. A second clinically-important efflux pump, AdeABC, also contributed to polyamine tolerance. Our results suggest that the disinfectant resistance capability that allows A. baumannii to survive in hospitals may have evolutionary origins in the transport of polyamine metabolites.
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2020 |
Li L, Hassan KA, Tetu SG, Naidu V, Pokhrel A, Cain AK, Paulsen IT, 'The Transcriptomic Signature of Tigecycline in Acinetobacter baumannii', Frontiers in Microbiology, 11 (2020) [C1] Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistance human pathogen Acinetobacter baumannii.... [more] Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistance human pathogen Acinetobacter baumannii. However, strains resistant to tigecycline were reported not long after its clinical introduction. Translation inhibitor antibiotics perturb ribosome function and induce the reduction of (p)ppGpp, an alarmone involved in the stringent response that negatively modulates ribosome production. Through RNA sequencing, this study revealed a significant reduction in the transcription of genes in citric acid cycle and cell respiration, suggesting tigecycline inhibits or slows down bacterial growth. Our results indicated that the drug-induced reduction of (p)ppGpp level promoted the production but diminished the degradation of ribosomes, which mitigates the translational inhibition effect by tigecycline. The reduction of (p)ppGpp also led to a decrease of transcription coupled nucleotide excision repair which likely increases the chances of development of tigecycline resistant mutants. Increased expression of genes linked to horizontal gene transfer were also observed. The most upregulated gene, rtcB, involving in RNA repair, is either a direct tigecycline stress response or is in response to the transcription de-repression of a toxin-antitoxin system. The most down-regulated genes encode two ß-lactamases, which is a possible by-product of tigecycline-induced reduction in transcription of genes associated with peptidoglycan biogenesis. This transcriptomics study provides a global genetic view of why A. baumannii is able to rapidly develop tigecycline resistance.
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2020 |
Alquethamy SF, Adams FG, Naidu V, Khorvash M, Pederick VG, Zang M, et al., 'The Role of Zinc Efflux during Acinetobacter baumannii Infection', ACS Infectious Diseases, 6 150-158 (2020) [C1]
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2019 |
Jiang JH, Hassan KA, Begg SL, Rupasinghe TWT, Naidu V, Pederick VG, et al., 'Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies', mBio, 10 (2019) [C1]
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2019 |
Hassan KA, Naidu V, Edgerton JR, Mettrick KA, Liu Q, Fahmy L, et al., 'Short-chain diamines are the physiological substrates of PACE family efflux pumps', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 18015-18020 (2019) [C1]
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2018 |
Hassan KA, Liu Q, Elbourne LDH, Ahmad I, Sharples D, Naidu V, et al., 'Pacing across the membrane: the novel PACE family of efflux pumps is widespread in Gram-negative pathogens', Research in Microbiology, 169 450-454 (2018) [C1]
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Show 9 more journal articles |
Preprint (1 outputs)
Year | Citation | Altmetrics | Link | |||||
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2023 |
Naidu V, Shah B, Maher C, Paulsen IT, Hassan KA, 'AedG, a new weapon in
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Grants and Funding
Summary
Number of grants | 9 |
---|---|
Total funding | $226,776 |
Click on a grant title below to expand the full details for that specific grant.
20235 grants / $119,776
Dial-on-demand: Engineering efflux pumps for microbial cell factories$25,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Dr. Bhumika Shah, Dr. Varsha Naidu, Dr. Jonathan Weinstein, Associate Professor Karl Hassan, Associate Professor Sarel Fleishman, Professor Ian Paulsen |
Scheme | ARC Centres of Excellence |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2024 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
Transport protein discovery and engineering for industrial biotechnology$25,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Dr. Varsha Naidu, Dr. Verlaine Timms, Dr. Liping Li, Dr. Lucie Semenec, Professor Ian Paulsen, Associate Professor Karl Hassan |
Scheme | ARC Centres of Excellence |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2024 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
A versatile and straightforward new method for evaluating protein-protein interactions and conformational changes$25,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Dr. Estefania Giannini, Dr. Varsha Naidu, Dr. Axayacatl Garcia, Dr. Bhumika Shah, Dr. Victoria Barja, Sasha Gohar, Prof. Ian Paulsen, Dr. Briardo Llorente |
Scheme | ARC Centres of Excellence |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2024 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
Illuminating the first steps of endosymbiosis: transcriptomics and metabolomics analyses of synthetic symbionts$25,000
Funding body: Bioplatforms Australia
Funding body | Bioplatforms Australia |
---|---|
Project Team | Dr Victoria Barja, Dr Esteban Marcelin, Dr Varsha Naidu, Sam Clay, Dr Dayane Costa, Dr Estefania Giannini, Professor Ian Paulsen, Dr Briardo Liorente |
Scheme | BPA OMICS RESEARCH PROJECT FUNDING SCHEME |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
Transport protein discovery and engineering for industrial biotechnology$19,776
Funding body: ARC Centre of Excellence in Synthetic Biology (CoESB)
Funding body | ARC Centre of Excellence in Synthetic Biology (CoESB) |
---|---|
Project Team | Doctor Varsha Naidu, Associate Professor Karl Hassan, Doctor Liping Li, Professor Ian Paulsen, Doctor Lucie Semenec, Doctor Verlaine Timms |
Scheme | EMCR Seed Funding Scheme |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2300392 |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | Y |
20221 grants / $25,000
Biosensor design & construction, Strain Construction Transposon library construction, TraDISense’n’Sort, Microbial Community design$25,000
Funding body: Bioplatforms Australia
Funding body | Bioplatforms Australia |
---|---|
Project Team | Karl Hassan, Evan Gibbs, Varsha Naidu, Amy Cain, Ian Paulsen, Brett Neilan |
Scheme | BPA OMICS RESEARCH PROJECT FUNDING SCHEME |
Role | Investigator |
Funding Start | 2022 |
Funding Finish | 2022 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
20182 grants / $7,000
Macquarie University Postgraduate Research Fund (PGRF) Travel Award$5,000
Funding body: Travel grant
Funding body | Travel grant |
---|---|
Scheme | Macquarie University |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
European Molecular Biology Laboratory (EMBL) Travel Award$2,000
Funding body: European Molecular Biology Laboratory (EMBL)
Funding body | European Molecular Biology Laboratory (EMBL) |
---|---|
Scheme | European Molecular Biology Laboratory (EMBL) Travel Award |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | |
Type Of Funding | International - Competitive |
Category | 3IFA |
UON | N |
20161 grants / $75,000
Australian Government Research Training Program (RTP) Award$75,000
Funding body: Australian Government
Funding body | Australian Government |
---|---|
Project Team | Varsha Naidu |
Scheme | Australian Government |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2019 |
GNo | |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | N |
Research Collaborations
The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.
Country | Count of Publications | |
---|---|---|
Australia | 12 | |
United Kingdom | 3 | |
Finland | 1 | |
United States | 1 |
Dr Varsha Naidu
Position
Post Doctoral Researcher
School of Environmental and Life Sciences
College of Engineering, Science and Environment
Contact Details
varsha.naidu@newcastle.edu.au | |
Link | Personal Blogs |