Skip to content
1887

Microbial Genomics logo Microbial Genomics

Volume 11, Issue 4

Taxonomic distribution of SbmA/BacA and BacA-like antimicrobial peptide transporters suggests independent recruitment and convergent evolution in host–microbe interactions Open Access

Abstract

Antimicrobial peptides (AMPs) are often produced by eukaryotes to control bacterial populations in both pathogenic and mutualistic symbioses. Several pathogens and nitrogen-fixing legume symbionts depend on transporters called SbmA (or BacA) or BclA (BacA-like) to survive exposure to AMPs. However, how broadly these transporters are distributed amongst bacteria, and their evolutionary history, is poorly understood. We used computational approaches, including phylogenetic and sequence similarity analyses, to examine the distribution of SbmA/BacA and BclA proteins across 1,255 species spanning the domain , leading to the identification of 71 and 177 SbmA/BacA and BclA proteins, respectively. sensitivity assays using legume AMPs and several BclA proteins confirmed that AMP transport is a common feature of BclA homologues. Our analyses indicated that SbmA/BacA homologues are encoded only by species in the phylum and are primarily found in just two orders: and . BclA homologues are somewhat more broadly distributed and were found in clusters across four phyla. These included several orders of the phyla and , the order (phylum ) and the class (phylum ). Many of the clades enriched for species encoding SbmA/BacA or BclA homologues are rich in species that interact with eukaryotic hosts in mutualistic or pathogenic interactions. These observations suggest that SbmA/BacA and BclA proteins have been repeatedly co-opted to facilitate associations with eukaryotic hosts by allowing bacteria to cope with host-encoded AMPs.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): molecular evolution , peptide transport , antimicrobial peptides , host–microbe interaction , pathogenesis and rhizobium-legume symbioses
Funding
This study was supported by the:
  • Agence Nationale de la Recherche (Award ANR-11-IDEX-0003)
    • Principal Award Recipient: PeterMergaert
  • Agence nationale de la recherche (Award ANR-17-EUR-0007)
    • Principal Award Recipient: BenoîtAlunni
  • Mitacs
    • Principal Award Recipient: AmiraBoukherissa
  • CNRS 80|PRIME – 2021
    • Principal Award Recipient: PeterMergaert
  • Natural Sciences and Engineering Research Council of Canada
    • Principal Award Recipient: GraemeW Howe
  • Queen’s University
    • Principal Award Recipient: GraemeW Howe
  • Natural Sciences and Engineering Research Council of Canada
    • Principal Award Recipient: GeorgeC diCenzo
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.001380
2025-04-16
2026-03-17

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/mgen/11/4/mgen001380.html?itemId=/content/journal/mgen/10.1099/mgen.0.001380&mimeType=html&fmt=ahah

References

  1. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol 2005; 3:238–250 [View Article] [PubMed]
     [Google Scholar]
  2. Le C-F, Fang C-M, Sekaran SD. Intracellular targeting mechanisms by antimicrobial peptides. Antimicrob Agents Chemother 2017; 61:02340–16 [View Article]
     [Google Scholar]
  3. Gebhard S. ABC transporters of antimicrobial peptides in firmicutes bacteria – phylogeny, function and regulation. Mol Microb 2012; 86:1295–1317 [View Article]
     [Google Scholar]
  4. Gruenheid S, Le Moual H. Resistance to antimicrobial peptides in gram-negative bacteria. FEMS Microbiol Lett 2012; 330:81–89 [View Article] [PubMed]
     [Google Scholar]
  5. Laviña M, Pugsley AP, Moreno F. Identification, mapping, cloning and characterization of a gene (sbmA) required for microcin B17 action on Escherichia coli K12. J Gen Microbiol 1986; 132:1685–1693 [View Article] [PubMed]
     [Google Scholar]
  6. Salomón RA, Farías RN. The peptide antibiotic microcin 25 is imported through the TonB pathway and the SbmA protein. J Bacteriol 1995; 177:3323–3325 [View Article] [PubMed]
     [Google Scholar]
  7. Guefrachi I, Pierre O, Timchenko T, Alunni B, Barrière Q et al. Bradyrhizobium BclA Is a Peptide Transporter Required for Bacterial Differentiation in Symbiosis with Aeschynomene Legumes. MPMI 2015; 28:1155–1166 [View Article]
     [Google Scholar]
  8. Domenech P, Kobayashi H, LeVier K, Walker GC, Barry CE 3rd. BacA, an ABC transporter involved in maintenance of chronic murine infections with mycobacterium tuberculosis. J Bacteriol 2009; 191:477–485 [View Article] [PubMed]
     [Google Scholar]
  9. Glazebrook J, Ichige A, Walker GC. A Rhizobium meliloti homolog of the Escherichia coli peptide-antibiotic transport protein SbmA is essential for bacteroid development. Genes Dev 1993; 7:1485–1497 [View Article] [PubMed]
     [Google Scholar]
  10. LeVier K, Phillips RW, Grippe VK, Roop RM, Walker GC. Similar requirements of a plant symbiont and a mammalian pathogen for prolonged intracellular survival. Science 2000; 287:2492–2493 [View Article] [PubMed]
     [Google Scholar]
  11. Li G, Laturnus C, Ewers C, Wieler LH. Identification of genes required for Avian Escherichia coli septicemia by signature-tagged mutagenesis. Infect Immun 2005; 73:2818–2827 [View Article]
     [Google Scholar]
  12. Ghilarov D, Inaba-Inoue S, Stepien P, Qu F, Michalczyk E et al. Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides. Sci Adv 2021; 7:eabj5363 [View Article] [PubMed]
     [Google Scholar]
  13. Runti G, Lopez Ruiz M del C, Stoilova T, Hussain R, Jennions M et al. Functional characterization of SbmA, a bacterial inner membrane transporter required for importing the antimicrobial peptide Bac7(1-35). J Bacteriol 2013; 195:5343–5351 [View Article] [PubMed]
     [Google Scholar]
  14. Haag AF, Baloban M, Sani M, Kerscher B, Pierre O et al. Protection of Sinorhizobium against host cysteine-rich antimicrobial peptides is critical for symbiosis. PLoS Biol 2011; 9:e1001169 [View Article] [PubMed]
     [Google Scholar]
  15. Mattiuzzo M, Bandiera A, Gennaro R, Benincasa M, Pacor S et al. Role of the Escherichia coli SbmA in the antimicrobial activity of proline-rich peptides. Mol Microbiol 2007; 66:151–163 [View Article] [PubMed]
     [Google Scholar]
  16. Metelev M, Osterman IA, Ghilarov D, Khabibullina NF, Yakimov A et al. Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel. Nat Chem Biol 2017; 13:1129–1136 [View Article] [PubMed]
     [Google Scholar]
  17. Nijland M, Lefebvre SN, Thangaratnarajah C, Slotboom DJ. Bidirectional ATP-driven transport of cobalamin by the mycobacterial ABC transporter BacA. Nat Commun 2024; 15:2626 [View Article] [PubMed]
     [Google Scholar]
  18. Travin DY, Jouan R, Vigouroux A, Inaba-Inoue S, Lachat J et al. Dual-uptake mode of the antibiotic phazolicin prevents resistance acquisition by gram-negative bacteria. mBio 2023; 14:e0021723 [View Article] [PubMed]
     [Google Scholar]
  19. Ferguson GP, Jansen A, Marlow VL, Walker GC. BacA-mediated bleomycin sensitivity in Sinorhizobium meliloti is independent of the unusual lipid a modification. J Bacteriol 2006; 188:3143–3148 [View Article] [PubMed]
     [Google Scholar]
  20. LeVier K, Walker GC. Genetic analysis of the Sinorhizobium meliloti BacA protein: differential effects of mutations on phenotypes. J Bacteriol 2001; 183:6444–6453 [View Article] [PubMed]
     [Google Scholar]
  21. Marlow VL, Haag AF, Kobayashi H, Fletcher V, Scocchi M et al. Essential role for the BacA protein in the uptake of a truncated eukaryotic peptide in Sinorhizobium meliloti. J Bacteriol 2009; 191:1519–1527 [View Article] [PubMed]
     [Google Scholar]
  22. Eswarappa SM, Panguluri KK, Hensel M, Chakravortty D. The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiol 2008; 154:666–678 [View Article] [PubMed]
     [Google Scholar]
  23. Nicoud Q, Barrière Q, Busset N, Dendene S, Travin D et al. Sinorhizobium meliloti functions required for resistance to antimicrobial NCR peptides and bacteroid differentiation. mBio 2021; 12: [View Article] [PubMed]
     [Google Scholar]
  24. Novikova M, Metlitskaya A, Datsenko K, Kazakov T, Kazakov A et al. The Escherichia coli Yej transporter is required for the uptake of translation inhibitor microcin C. J Bacteriol 2007; 189:8361–8365 [View Article] [PubMed]
     [Google Scholar]
  25. Wang Z, Bie P, Cheng J, Lu L, Cui B et al. The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis. Sci Rep 2016; 6:31876 [View Article]
     [Google Scholar]
  26. Czernic P, Gully D, Cartieaux F, Moulin L, Guefrachi I et al. Convergent evolution of endosymbiont differentiation in dalbergioid and inverted repeat-lacking clade legumes mediated by nodule-specific cysteine-rich peptides. Plant Physiol 2015; 169:1254–1265 [View Article] [PubMed]
     [Google Scholar]
  27. Huang R, Snedden WA, diCenzo GC. Reference nodule transcriptomes for melilotus officinalis and medicago sativa cv. Algonquin. Algonquin Plant Direct 2022; 6:e408 [View Article]
     [Google Scholar]
  28. Kereszt A, Mergaert P, Montiel J, Endre G, Kondorosi É. Impact of plant peptides on symbiotic nodule development and functioning. Front Plant Sci 2018; 9:1026 [View Article] [PubMed]
     [Google Scholar]
  29. Montiel J, Downie JA, Farkas A, Bihari P, Herczeg R et al. Morphotype of bacteroids in different legumes correlates with the number and type of symbiotic NCR peptides. Proc Natl Acad Sci USA 2017; 114:5041–5046 [View Article] [PubMed]
     [Google Scholar]
  30. Van de Velde W, Zehirov G, Szatmari A, Debreczeny M, Ishihara H et al. Plant peptides govern terminal differentiation of bacteria in symbiosis. Science 2010; 327:1122–1126 [View Article] [PubMed]
     [Google Scholar]
  31. Farkas A, Maróti G, Durgő H, Györgypál Z, Lima RM et al. Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms. Proc Natl Acad Sci USA 2014; 111:5183–5188 [View Article] [PubMed]
     [Google Scholar]
  32. diCenzo GC, Zamani M, Ludwig HN, Finan TM. Heterologous complementation reveals a specialized activity for BacA in the Medicago – Sinorhizobium meliloti symbiosis. MPMI 2017; 30:312–324 [View Article]
     [Google Scholar]
  33. Travin DY, Watson ZL, Metelev M, Ward FR, Osterman IA et al. Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition. Nat Commun 2019; 10:4563 [View Article] [PubMed]
     [Google Scholar]
  34. Santos-Júnior CD, Torres MDT, Duan Y, Rodríguez Del Río Á, Schmidt TSB et al. Discovery of antimicrobial peptides in the global microbiome with machine learning. Cell 2024; 187:3761–3778 [View Article] [PubMed]
     [Google Scholar]
  35. Arnold MFF, Haag AF, Capewell S, Boshoff HI, James EK et al. Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein. J Bacteriol 2013; 195:389–398 [View Article] [PubMed]
     [Google Scholar]
  36. Wells DH, Long SR. The Sinorhizobium meliloti stringent response affects multiple aspects of symbiosis. Mol Microbiol 2002; 43:1115–1127 [View Article] [PubMed]
     [Google Scholar]
  37. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9:357–359 [View Article] [PubMed]
     [Google Scholar]
  38. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES et al. Integrative genomics viewer. Nat Biotechnol 2011; 29:24–26 [View Article]
     [Google Scholar]
  39. Barrière Q, Guefrachi I, Gully D, Lamouche F, Pierre O et al. Integrated roles of BclA and DD-carboxypeptidase 1 in bradyrhizobium differentiation within NCR-producing and NCR-lacking root nodules. Sci Rep 2017; 7:9063 [View Article] [PubMed]
     [Google Scholar]
  40. Finan TM, Kunkel B, De Vos GF, Signer ER. Second symbiotic megaplasmid in Rhizobium meliloti carrying exopolysaccharide and thiamine synthesis genes. J Bacteriol 1986; 167:66–72 [View Article] [PubMed]
     [Google Scholar]
  41. Jensen HL. Nitrogen fixation in leguminous plants. I. general characters of root-nodule bacteria isolated from species of medicago and trifolium in australia. Proc Lin Soc New South Wales 1942; 67:98–108
     [Google Scholar]
  42. diCenzo GC, Mengoni A, Perrin E. Chromids aid genome expansion and functional diversification in the family Burkholderiaceae. Mol Biol and Evol 2019; 36:562–574 [View Article]
     [Google Scholar]
  43. Johnson LS, Eddy SR, Portugaly E. Hidden markov model speed heuristic and iterative HMM search procedure. BMC Bioinform 2010; 11:431 [View Article]
     [Google Scholar]
  44. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K et al. Fast, scalable generation of high-quality protein multiple sequence alignments using clustal omega. Mol Syst Biol 2011; 7:539 [View Article] [PubMed]
     [Google Scholar]
  45. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013; 30:772–780 [View Article] [PubMed]
     [Google Scholar]
  46. Notredame C, Higgins DG, Heringa J. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol 2000; 302:205–217 [View Article] [PubMed]
     [Google Scholar]
  47. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinform 2009; 25:1972–1973 [View Article] [PubMed]
     [Google Scholar]
  48. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era. Mol Biol and Evol 2020; 37:1530–1534 [View Article]
     [Google Scholar]
  49. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
     [Google Scholar]
  50. Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 2010; 59:307–321 [View Article] [PubMed]
     [Google Scholar]
  51. Letunic I, Bork P. Interactive tree of life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool. Nucleic Acids Res 2024; 52:W78–W82 [View Article] [PubMed]
     [Google Scholar]
  52. Oberg N, Zallot R, Gerlt JA. EFI-EST, EFI-GNT, and EFI-CGFP: enzyme function initiative (EFI) web resource for genomic enzymology tools. J Mol Biol 2023; 435:168018 [View Article] [PubMed]
     [Google Scholar]
  53. Zallot R, Oberg N, Gerlt JA. The EFI web resource for genomic enzymology tools: leveraging protein, genome, and metagenome databases to discover novel enzymes and metabolic pathways. Biochemistry 2019; 58:4169–4182 [View Article] [PubMed]
     [Google Scholar]
  54. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13:2498–2504 [View Article] [PubMed]
     [Google Scholar]
  55. Wu M, Scott AJ. Phylogenomic analysis of bacterial and archaeal sequences with AMPHORA2. Bioinform 2012; 28:1033–1034 [View Article] [PubMed]
     [Google Scholar]
  56. Sankari S, Babu VMP, Bian K, Alhhazmi A, Andorfer MC et al. A haem-sequestering plant peptide promotes iron uptake in symbiotic bacteria. Nat Microbiol 2022; 7:1453–1465 [View Article] [PubMed]
     [Google Scholar]
  57. Maruya J, Saeki K. The bacA gene homolog, mlr7400, in mesorhizobium loti MAFF303099 is dispensable for symbiosis with Lotus japonicus but partially capable of supporting the symbiotic function of bacA in Sinorhizobium meliloti. Plant Cell Physiol 2010; 51:1443–1452 [View Article] [PubMed]
     [Google Scholar]
  58. diCenzo GC, Yang Y, Young JPW, Kuzmanović N. Refining the taxonomy of the order Hyphomicrobiales (Rhizobiales) based on whole genome comparisons of over 130 type strains. Int J Syst Evol Microbiol 2024; 74:006328 [View Article] [PubMed]
     [Google Scholar]
  59. de la Maza LM, Pezzlo MT, Bittencourt CE, Peterson EM. Introduction to Enterobacterales. In Color Atlas of Medical Bacteriology John Wiley & Sons, Ltd; 2020 pp 91–102 [View Article]
     [Google Scholar]
  60. Garrity GM, Bell JA, Lilburn T. Pasteurellales ord. nov. In Brenner DJ, Krieg NR, Staley JT, Garrity GM, Boone DR et al. eds Bergey’s Manual® of Systematic Bacteriology US: Springer; 2005 pp 850–912 [View Article]
     [Google Scholar]
  61. Dobritsa AP, Samadpour M. Transfer of eleven species of the genus Burkholderia to the genus Paraburkholderia and proposal of Caballeronia gen. nov. to accommodate twelve species of the genera Burkholderia and Paraburkholderia. Int J Syst Evol Microbiol 2016; 66:2836–2846 [View Article] [PubMed]
     [Google Scholar]
  62. Voronina OL, Kunda MS, Ryzhova NN, Aksenova EI, Semenov AN et al. The variability of the order Burkholderiales representatives in the healthcare units. Biomed Res Int 2015; 2015:680210 [View Article] [PubMed]
     [Google Scholar]
  63. Chen S, Rudra B, Gupta RS. Phylogenomics and molecular signatures support division of the order Neisseriales into emended families Neisseriaceae and Chromobacteriaceae and three new families Aquaspirillaceae fam. nov., Chitinibacteraceae fam. nov., and Leeiaceae fam. nov. Syst Appl Microbiol 2021; 44:126251 [View Article] [PubMed]
     [Google Scholar]
  64. Bergman B, Johansson C, Söderbäck E. The Nostoc-Gunnera symbiosis. New Phytol 1992; 122:379–400 [View Article] [PubMed]
     [Google Scholar]
  65. Mutalipassi M, Riccio G, Mazzella V, Galasso C, Somma E et al. Symbioses of cyanobacteria in marine environments: ecological insights and biotechnological perspectives. Mar Drugs 2021; 19:227 [View Article] [PubMed]
     [Google Scholar]
  66. Val-Calvo J, Vázquez-Boland JA. Mycobacteriales taxonomy using network analysis-aided, context-uniform phylogenomic approach for non-subjective genus demarcation. mBio 2023; 14:e0220723 [View Article] [PubMed]
     [Google Scholar]
  67. Morgado S, Ramos N de V, Pereira BB do N, Freitas F, da Fonseca ÉL et al. Multidrug-resistant Mycolicibacterium fortuitum infection in a companion cat (Felis silvestris catus) in Brazil. Access Microbiol 2022; 4:000317 [View Article] [PubMed]
     [Google Scholar]
  68. Antunes LC, Poppleton D, Klingl A, Criscuolo A, Dupuy B et al. Phylogenomic analysis supports the ancestral presence of LPS-outer membranes in the firmicutes. Elife 2016; 5:e14589 [View Article] [PubMed]
     [Google Scholar]
  69. Brown RF. Investigating the Evolutionary Origin and Cell Biology of Negativicutes. Warwick: University of Warwick; 2016
  70. Rahimlou S, Bahram M, Tedersoo L. Phylogenomics reveals the evolution of root nodulating alpha- and beta-proteobacteria (rhizobia). Microbiol Res 2021; 250:126788 [View Article] [PubMed]
     [Google Scholar]
  71. Lavin M, Herendeen PS, Wojciechowski MF. Evolutionary rates analysis of leguminosae implicates a rapid diversification of lineages during the tertiary. Syst Biol 2005; 54:575–594 [View Article] [PubMed]
     [Google Scholar]
  72. Oulas A, Zachariou M, Chasapis CT, Tomazou M, Ijaz UZ et al. Putative antimicrobial peptides within bacterial proteomes affect bacterial predominance: a network analysis perspective. Front Microbiol 2021; 12:752674 [View Article] [PubMed]
     [Google Scholar]
  73. Parker JK, Davies BW. Microcins reveal natural mechanisms of bacterial manipulation to inform therapeutic development. Microbiol 2022; 168:001175 [View Article] [PubMed]
     [Google Scholar]
  74. Ichige A, Walker GC. Genetic analysis of the Rhizobium meliloti bacA gene: functional interchangeability with the Escherichia coli sbmA gene and phenotypes of mutants. J Bacteriol 1997; 179:209–216 [View Article] [PubMed]
     [Google Scholar]
  75. Schober I, Koblitz J, Sardà Carbasse J, Ebeling C, Schmidt ML et al. BacDive in 2025: the core database for prokaryotic strain data. Nucleic Acids Res 2025; 53:D748–D756 [View Article] [PubMed]
     [Google Scholar]
/content/journal/mgen/10.1099/mgen.0.001380
Loading
Taxonomic distribution of SbmA/BacA and BacA-like antimicrobial peptide transporters suggests independent recruitment and convergent evolution in host–microbe interactions
M Gen 11, 001380 (2025); https://doi.org/10.1099/mgen.0.001380
/content/journal/mgen/10.1099/mgen.0.001380
/content/journal/mgen/10.1099/mgen.0.001380
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Supplementary material 3

EXCEL

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An error occurred
Approval was partially successful, following selected items could not be processed due to error