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Abstract

Genes encoding a novel multidrug efflux pump, AadT, from the Drug:H antiporter 2 family, were discovered in multidrug resistance plasmids. Here, we profiled the antimicrobial resistance potential, and examined the distribution of these genes. homologs were found in many and other Gram-negative species and were typically adjacent to novel variants of ), which encodes a major tripartite efflux pump in . The AadT pump decreased bacterial susceptibility to at least eight diverse 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 resistance arsenal and may cooperate with variants of AdeAB(C).

Funding
This study was supported by the:
  • National Health and Medical Research Council (Award GNT1120298)
    • Principle Award Recipient: KarlA. Hassan
  • Australian Research Council (Award FT180100123)
    • Principle Award Recipient: KarlA. Hassan
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/micro/10.1099/mic.0.001341
2023-05-30
2024-11-02
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References

  1. Brzoska AJ, Hassan KA, de Leon EJ, Paulsen IT, Lewis PJ. Single-step selection of drug resistant Acinetobacter baylyi ADP1 mutants reveals a functional redundancy in the recruitment of multidrug efflux systems. PLoS One 2013; 8:e56090 [View Article] [PubMed]
    [Google Scholar]
  2. Hassan KA, Maher C, Elbourne LD, Henderson PJ, Paulsen IT. Increasing the PACE of characterising novel transporters by functional genomics. Curr Opin Microbiol 2021; 64:1–8 [View Article] [PubMed]
    [Google Scholar]
  3. Henderson PJF, Maher C, Elbourne LDH, Eijkelkamp BA, Paulsen IT et al. Physiological functions of bacterial “multidrug” efflux pumps. Chem Rev 2021; 121:5417–5478 [View Article] [PubMed]
    [Google Scholar]
  4. Bi D, Zheng J, Xie R, Zhu Y, Wei R et al. Comparative analysis of AbaR-type genomic islands reveals distinct patterns of genetic features in elements with different backbones. mSphere 2020; 5:e00349-20 [View Article] [PubMed]
    [Google Scholar]
  5. Guardabassi L, Dijkshoorn L, Collard JM, Olsen JE, Dalsgaard A. Distribution and in-vitro transfer of tetracycline resistance determinants in clinical and aquatic Acinetobacter strains. J Med Microbiol 2000; 49:929–936 [View Article] [PubMed]
    [Google Scholar]
  6. Levy SB, Mcmurry L. Plasmid-determined tetracycline resistance involves new transport systems for tetracycline. Nature 1978; 276:90–92 [View Article]
    [Google Scholar]
  7. Li L, Hassan KA, Brown MH, Paulsen IT. Rapid multiplexed phenotypic screening identifies drug resistance functions for three novel efflux pumps in Acinetobacter baumannii. J Antimicrob Chemother 2016; 71:1223–1232 [View Article] [PubMed]
    [Google Scholar]
  8. Naidu V, Bartczak A, Brzoska AJ, Lewis P, Eijkelkamp BA et al. Evolution of RND efflux pumps in the development of a successful pathogen. Drug Resist Updat 2023; 66:100911 [View Article] [PubMed]
    [Google Scholar]
  9. Hassan KA, Brzoska AJ, Wilson NL, Eijkelkamp BA, Brown MH et al. Roles of DHA2 family transporters in drug resistance and iron homeostasis in Acinetobacter spp. Microb Physiol 2011; 20:116–124 [View Article]
    [Google Scholar]
  10. Stark MJ. Multicopy expression vectors carrying the lac repressor gene for regulated high-level expression of genes in Escherichia coli. Gene 1987; 51:255–267 [View Article] [PubMed]
    [Google Scholar]
  11. Wiegand I, Hilpert K, Hancock REW. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 2008; 3:163–175 [View Article] [PubMed]
    [Google Scholar]
  12. Gilchrist CLM, Chooi YH. clinker & clustermap.js: automatic generation of gene cluster comparison figures. Bioinformatics 2021; 37:2473–2475 [View Article] [PubMed]
    [Google Scholar]
  13. Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004; 5:113 [View Article] [PubMed]
    [Google Scholar]
  14. Huelsenbeck JP, Ronquist F. MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 2001; 17:754–755 [View Article] [PubMed]
    [Google Scholar]
  15. Campanella JJ, Bitincka L, Smalley J. MatGAT: an application that generates similarity/identity matrices using protein or DNA sequences. BMC Bioinformatics 2003; 4:29 [View Article] [PubMed]
    [Google Scholar]
  16. Marchand I, Damier-Piolle L, Courvalin P, Lambert T. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 2004; 48:3298–3304 [View Article] [PubMed]
    [Google Scholar]
  17. Sugawara E, Nikaido H. Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob Agents Chemother 2014; 58:7250–7257 [View Article] [PubMed]
    [Google Scholar]
  18. Tal N, Schuldiner S. A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci 2009; 106:9051–9056 [View Article]
    [Google Scholar]
  19. Rajamohan G, Srinivasan VB, Gebreyes WA. Molecular and functional characterization of a novel efflux pump, AmvA, mediating antimicrobial and disinfectant resistance in Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:1919–1925 [View Article] [PubMed]
    [Google Scholar]
  20. Santiviago CA, Fuentes JA, Bueno SM, Trombert AN, Hildago AA et al. The Salmonella enterica sv. Typhimurium smvA, yddG and ompD (porin) genes are required for the efficient efflux of methyl viologen. Mol Microbiol 2002; 46:687–698 [View Article] [PubMed]
    [Google Scholar]
  21. Short FL, Liu Q, Shah B, Clift HE, Naidu V et al. The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump. Commun Biol 2021; 4:1114 [View Article] [PubMed]
    [Google Scholar]
  22. Lee A, Mao W, Warren MS, Mistry A, Hoshino K et al. Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol 2000; 182:3142–3150 [View Article] [PubMed]
    [Google Scholar]
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