ORCID Profile
0000-0002-7668-9583
Current Organisations
The University of Newcastle - Newcastle City Campus
,
Macquarie University
,
University of Oxford
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Publisher: Proceedings of the National Academy of Sciences
Date: 15-08-2019
Abstract: Multidrug efflux pumps are highly promiscuous determinants of antimicrobial resistance in bacterial pathogens. Since efflux pumps evolved long before the widespread use of antimicrobials, drug transport is likely to be a side reaction in many pumps, fortuitously beneficial to bacteria in hospitals. The AceI efflux protein from Acinetobacter baumannii is the prototype for the proteobacterial antimicrobial compound efflux (PACE) family. AceI was only known to transport the synthetic biocide chlorhexidine, which was incongruous with its ancient origin. Here we demonstrate that short-chain diamines are the physiological substrates of AceI and other PACE members, and that transport is energized by an electrochemical gradient of protons. These observations are important, because diamines play vital roles in bacterial physiology and virulence and have significant commercial uses.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2021
DOI: 10.1038/S42003-021-02629-6
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 03-01-2023
DOI: 10.1101/2023.01.03.522653
Abstract: A novel multidrug efflux pump, AadT from the Drug:H + antiporter 2 family, was discovered in Acinetobacter multidrug resistance plasmids. Here, we profiled the antimicrobial resistance potential and examined the distribution of this gene. Putative homologs of this efflux pump were encoded in many Acinetobacter species and other Gram-negative species, and were genetically associated with novel variants of adeAB(C) , which encodes a major tripartite efflux pump in Acinetobacter . The AadT pump conferred decreased susceptibility to at least eight erse antimicrobials, including antibiotics erythromycin, tetracycline biocides chlorhexidine and dyes ethidium bromide and DAPI. These results show that AadT is a new determinant in the Acinetobacter resistance arsenal and may cooperate with variants of AdeAB(C).
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2023
DOI: 10.1101/2023.07.26.550637
Abstract: Benzalkonium chloride (BAC) is widely used in many disinfectant solutions in clinical settings to eradicate potential bacterial pathogens, such as Acinetobacter baumannii . We sought to investigate the transcriptomic response of a drug resistant A. baumannii isolate, AB5075-UW, on exposure to a sub-inhibitory concentration of BAC. Our transcriptomic analysis found that BAC caused an increase in the expression of genes associated with protein synthesis, such as translation initiation factors, ribosomal proteins and tRNA synthetases. It also induced the expression of genes associated with energy production and central carbon metabolism. We also observed increased expression of peptidoglycan and rod shape determining genes, which may provide increased mechanical strength to withstand osmotic challenges posed by compounds such as BAC. The most highly expressed genes under BAC stress include those that encode the RND efflux pump AdeABC and the A. baumannii porin Omp33. Mutants of adeABC and its regulator genes adeRS had a higher susceptibility to BAC. Disruption of the gene encoding Omp33 also resulted in higher susceptibility to BAC, and complementation of the mutant with omp33 together with a 450bp upstream region restored tolerance to BAC to parental strain levels (AB5075-UW). Site directed mutagenesis of amino acids associated with Omp33 periplasmic turn (T1), which folds into the lumen of the porin and blocks the channel, suggests that Omp33 may act to prevent entry of BAC into the cell. In previous studies, Omp33 has been described as an important virulence factor in A. baumannii. The results presented in this study describe a novel role for Omp33 in BAC tolerance and reveal that A. baumannii tolerates BAC stress through a combination of mechanisms.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-08-2022
Abstract: The use of spoken and written language is a fundamental human capacity. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in s les of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.
Publisher: American Society for Microbiology
Date: 18-05-2021
DOI: 10.1128/AAC.01400-20
Abstract: 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 .
Publisher: Springer Science and Business Media LLC
Date: 09-10-2023
Publisher: American Society for Microbiology
Date: 29-06-2021
Abstract: 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.
Publisher: Elsevier BV
Date: 09-2018
Publisher: American Chemical Society (ACS)
Date: 28-10-2019
Publisher: Frontiers Media SA
Date: 27-10-2020
Publisher: Microbiology Society
Date: 30-05-2023
DOI: 10.1099/MIC.0.001341
Abstract: Genes encoding a novel multidrug efflux pump, AadT, from the Drug:H + antiporter 2 family, were discovered in Acinetobacter multidrug resistance plasmids. Here, we profiled the antimicrobial resistance potential, and examined the distribution of these genes. aadT homologs were found in many Acinetobacter and other Gram-negative species and were typically adjacent to novel variants of adeAB(C ), which encodes a major tripartite efflux pump in Acinetobacter . The AadT pump decreased bacterial susceptibility to at least eight erse antimicrobials, including antibiotics (erythromycin and tetracycline), biocides (chlorhexidine), and dyes (ethidium bromide and DAPI) and was able to mediate ethidium transport. These results show that AadT is a multidrug efflux pump in the Acinetobacter resistance arsenal and may cooperate with variants of AdeAB(C).
Publisher: American Society for Microbiology
Date: 20-10-2022
DOI: 10.1128/MRA.00317-22
Abstract: Here, we report the 7.7-Mbp genome sequence of Rhodococcus sp. strain 9, which was isolated from Australian groundwater contaminated with phenols and trichloroethylene. This strain has previously been shown to efficiently degrade p -nitrophenol and high-molecular-weight polycyclic aromatic hydrocarbons (PAHs).
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2021
DOI: 10.1101/2021.11.04.466897
Abstract: The use of spoken and written language is a capacity that is unique to humans. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total s le sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10 −8 ) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.
Publisher: American Society for Microbiology
Date: 26-02-2019
Abstract: A shift in the Western diet since the industrial revolution has resulted in a dramatic increase in the consumption of omega-6 fatty acids, with a concurrent decrease in the consumption of omega-3 fatty acids. This decrease in omega-3 fatty acid consumption has been associated with significant disease burden, including increased susceptibility to infectious diseases. Here we provide evidence that DHA, an omega-3 fatty acid, has superior antimicrobial effects upon the highly drug-resistant pathogen Acinetobacter baumannii , thereby providing insights into one of the potential health benefits of omega-3 fatty acids. The identification and characterization of two novel bacterial membrane protective mechanisms against host fatty acids provide important insights into A. baumannii adaptation during disease. Furthermore, we describe a novel role for the major multidrug efflux system AdeIJK in A. baumannii membrane maintenance and lipid transport. This core function, beyond drug efflux, increases the appeal of AdeIJK as a therapeutic target.
Publisher: Elsevier BV
Date: 2023
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Varsha Naidu, PhD.