RND pumps across the<i>Acinetobacter</i>genus; AdeIJK is the ancestral efflux system

Darby, Elizabeth M; Bavro, Vassiliy N.; Dunn, Steven; McNally, Alan; Blair, Jessica M A

doi:10.1101/2022.10.19.512856

Cited by 2 publications

(3 citation statements)

References 82 publications

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“…Across the Gram-negative bacteria it is generally assumed that efflux pump sequences are conserved across a species, with genes present in common laboratory strains often taken as representatives of a whole species. This is despite several studies demonstrating that clinical isolates of Acinetobacter baumannii can lack adeB, which encodes the RND component of the AdeABC system associated with reduced antimicrobial susceptibility [32][33][34]. Here we show that while it is assumed that all E. coli isolates possess AcrB, AcrD, AcrF, CusA, MdtBC and MdtF, this is not true for the ST11 lineage.…”

Section: Discussioncontrasting

confidence: 83%

E. coli ST11 (O157:H7) does not encode a functional AcrF efflux pump

et al. 2023

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Escherichia coli is a facultative anaerobe found in a wide range of environments. Commonly described as the laboratory workhorse, E. coli is one of the best characterized bacterial species to date, however much of our understanding comes from studies involving the laboratory strain E. coli K-12. Resistance-nodulation-division efflux pumps are found in Gram-negative bacteria and can export a diverse range of substrates, including antibiotics. E. coli K-12 has six RND pumps; AcrB, AcrD, AcrF, CusA, MdtBC and MdtF, and it is frequently reported that all E. coli strains possess these six pumps. However, this is not true of E. coli ST11, a lineage of E. coli , which is primarily composed of the highly virulent important human pathogen, E. coli O157:H7. Here we show that acrF is absent from the pangenome of ST11 and that this lineage of E. coli has a highly conserved insertion within the acrF gene, which when translated encodes 13 amino acids and two stop codons. This insertion was found to be present in 97.59 % of 1787 ST11 genome assemblies. Non-function of AcrF in ST11 was confirmed in the laboratory as complementation with acrF from ST11 was unable to restore AcrF function in E. coli K-12 substr. MG1655 ΔacrB ΔacrF. This shows that the complement of RND efflux pumps present in laboratory bacterial strains may not reflect the situation in virulent strains of bacterial pathogens.

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Section: Discussioncontrasting

confidence: 83%

E. coli ST11 (O157:H7) does not encode a functional AcrF efflux pump

et al. 2023

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“…The number of RND pumps present in different Gram-negative bacterial species varies and there is increasing evidence that prevalence of RND efflux pumps can also vary between isolates of the same species (Darby et al, 2023, Leus et al, 2020, Nowak et al, 2015, Nemec et al, 2007, Wieczorek et al, 2013). Yet it is still broadly assumed that all E. coli isolates possess six RND efflux pumps despite recent work…”

Section: Discussionmentioning

confidence: 99%

“…However, the number of RND pumps can also vary within a genus. For example, we have recently shown that species across the Acinetobacter genus possess between two and nine RND pumps, with species most-commonly associated with human infection tending to encode more RND efflux pumps (Darby et al, 2023). A study by Ma et al found loss of MtrC function correlated with increased drug susceptibility in N. gonorrhoeae isolated from the cervical environment (Ma et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The RND efflux pump EefABC is highly conserved within lineages ofE. colicommonly associated with infection

Pugh,

Darby,

Burgess

et al. 2024

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Tripartite resistance-nodulation-division (RND) efflux pumps confer multidrug resistance (MDR) in Gram-negative bacteria and are critical for many physiological functions including virulence and biofilm formation. The common laboratory strain ofE. coli,K-12 MG1655 has six recognised RND transporters participating in tripartite pump formation (AcrB, AcrD, AcrF, CusA, MdtBC, and MdtF). However, by studying >20,000E. coligenomes we show thatE. colibelonging to phylogroups B2, D, E, F and G, which are commonly associated with infection, possess an additional, seventh RND transporter, EefB. It is found in a five gene operon,eefRABCD,which also encodes a TetR family transcription factor, a periplasmic adapter protein, an outer membrane factor and major facilitator superfamily pump. In contrast,E. colifrom phylogroups A, B1 and C, generally containing environmental and commensal strains, do not encode the operon and instead encode an uncharacterised ORF,ycjD. In phylogroups where theeefRABCDoperon is present it was very highly conserved. In fact, conservation levels were comparable to that of the majorE. coliRND efflux system AcrAB-TolC, suggesting a critical biological function. Protein modelling shows that this pump is highly divergent from endogenousE. coliRND systems with unique structural features, while showing similarities to efflux systems found inPseudomonas aeruginosa. However, unlike other major RND efflux systems, EefABC does not appear to transport antimicrobials and instead may be important for infection or survival in the host environment.ImportanceEfflux pumps are molecular machines that export molecules out of bacterial cells. The efflux pumps belonging to the RND family are particularly important as they export antibiotics out of Gram-negative bacterial cells, contributing to antibiotic resistance. The important human pathogen,E. coli, has been previously reported to have six RND pumps. However, we show that phylogroups ofE. colicommonly associated with infection encode a seventh RND pump, EefABC which is highly conserved, suggesting an important biological function. While the function of EefABC inE. coliremains to be resolved, it does not seem to transport antimicrobial compounds. These findings are important because they reveal a new RND pump, potentially involved in virulence and survival in the host, that could represent a new therapeutic target. Additionally, it again shows that laboratory type strains of common bacterial pathogens are not representative of those that are infection causing.

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RND pumps across theAcinetobactergenus; AdeIJK is the ancestral efflux system

Cited by 2 publications

References 82 publications

E. coli ST11 (O157:H7) does not encode a functional AcrF efflux pump

E. coli ST11 (O157:H7) does not encode a functional AcrF efflux pump

The RND efflux pump EefABC is highly conserved within lineages ofE. colicommonly associated with infection

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