The putative drug efflux systems of the Bacillus cereus group

Abstract

The Bacillus cereus group of bacteria includes seven closely related species, three of which, B. anthracis, B. cereus and B. thuringiensis, are pathogens of humans, animals and/or insects. Preliminary investigations into the transport capabilities of different bacterial lineages suggested that genes encoding putative efflux systems were unusually abundant in the B. cereus group compared to other bacteria. To explore the drug efflux potential of the B. cereus group all putative efflux systems were identified in the genomes of prototypical strains of B. cereus, B. anthracis and B. thuringiensis using our Transporter Automated Annotation Pipeline. More than 90 putative drug efflux systems were found within each of these strains, accounting for up to 2.7% of their protein coding potential. Comparative analyses demonstrated that the efflux systems are highly conserved between these species; 70–80% of the putative efflux pumps were shared between all three strains studied. Furthermore, 82% of the putative efflux system proteins encoded by the prototypical B. cereus strain ATCC 14579 (type strain) were found to be conserved in at least 80% of 169 B. cereus group strains that have high quality genome sequences available. However, only a handful of these efflux pumps have been functionally characterized. Deletion of individual efflux pump genes from B. cereus typically had little impact to drug resistance phenotypes or the general fitness of the strains, possibly because of the large numbers of alternative efflux systems that may have overlapping substrate specificities. Therefore, to gain insight into the possible transport functions of efflux systems in B. cereus, we undertook large-scale qRT-PCR analyses of efflux pump gene expression following drug shocks and other stress treatments. Clustering of gene expression changes identified several groups of similarly regulated systems that may have overlapping drug resistance functions. In this article we review current knowledge of the small molecule efflux pumps encoded by the B. cereus group and suggest the likely functions of numerous uncharacterised pumps.

Peeling the Layers Away: The Genomic Characterization of Bacillus pumilus 64-1, an Isolate With Antimicrobial Activity From the Marine Sponge Plakina cyanorosea (Porifera, Homoscleromorpha)

“…Genes for transcriptional regulators involved with antibiotic resistance, such as TetR and MarR, and for the response regulator OmpR, were also identified in the B. pumilus 64-1 genome ( Supplementary Table 4 ), showing that the B. pumilus 64-1 strain may be able to control the expression of these genes under the conditions imposed by these antagonist compounds. Moreover, the functional annotation of multidrug resistance proteins ( ykkC , ykkD , ebrA , ebrB , mdtI , and sugE ) and multidrug efflux pumps ( yhbJ and norM ), including those from the multidrug and toxic compound extrusion (MATE) family ( yisQ and yoeA ) and the RND (resistance-nodulation-cell division) drug exporters ( ydgH , mdtC , and swrC ), suggest a wider intrinsic resistance, as verified for the B. cereus group, either for their chloramphenicol and tetracycline genetic repertoire ( Glenwright et al, 2017 ) or by the conservation of these small molecules efflux pumps ( Hassan et al, 2017 ). This apparent intrinsic resistance genotype of the strain 64-1 may not only form part of defense strategies against the ever-changing environmental conditions but also for physiological processes, considering that some of the substrates for these multidrug transporters are cations, such as Na + and H + ( Du et al, 2018 ).…”

Control of metabolite efflux in microbial cell factories: current advances and future prospects

“…However, this is not particularly reliable as most transporters have undergone divergent evolution [187] such that moderately similar sequences or motifs can have considerably different substrates. (Note that efflux systems do seem to be more strongly conserved than are influx systems [188], and are often highly promiscuous [68,134]. )…”

Towards the minimal proteome of life: Proteome profiles ofBacillus subtilisvegetative cells and spores

“…EcsA,a regulator of protein secretion27 , is essential in sporulation24 and might play a role in germination due to its inherent protein transporting capacity. The uncharacterized proteins YvrC, YkpA, YdbJ, YfmR, YknZ, YhaQ, YfmM and YhfQ from ABC transporter family are also shared by spores and cells of which YhfQ is has been linked to siderophore uptake28 .The B. cereus orthologs of YfmM and YdbJ (BC5433 and BC1359 respectively), as well as of YknZ (BC5253) are reported to be functional drug efflux pumps, more specifically for the latter is a macrolide exporter29 . Also the orthologs of YhaQ, BerA in B. thuringiensis and BcrA in B. licheniformis are concerned with β -exotoxin30 and bacitracin 31 resistance respectively.…”