The putative drug efflux systems of the Bacillus cereus group

PLoS One. 2017 May 4;12(5):e0176188. doi: 10.1371/journal.pone.0176188. eCollection 2017.

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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacillus cereus / drug effects
  • Bacillus cereus / genetics
  • Bacillus cereus / metabolism*
  • Biological Transport
  • Genes, Bacterial
  • Microbial Sensitivity Tests
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Anti-Bacterial Agents

Grants and funding

This research was funded by the Norwegian Research Council (FUGE II Program, Project ID 183421) to ABK and OAØ, an Australian National Health and Medical Research Council Project Grant (1060895) to ITP, KAH and PJFH, an Australian Academy of Science Grant (247634) and a Research Development Grant from Macquarie University to KAH and LDHE (9201401563). KAH thanks the EU for the award of a Marie Slowdoska Curie Research Fellowship and PJFH thanks the Leverhulme Trust for an Emeritus Research Fellowship. Consortium collaborations between laboratories (ABK, PJFH, ITP) are funded by the EU BacMT and ATENS initiatives.