Occurrence and Potential Mechanism of Holin-mediated Non-lytic Protein Translocation in Bacteria

Overview

Journal Microb Cell

Specialty Microbiology

Date 2022 Oct 20

PMID 36262927

Authors

Thomas Bruser

Denise Mehner-Breitfeld

Affiliations

Soon will be listed here.

Abstract

Holins are generally believed to generate large membrane lesions that permit the passage of endolysins across the cytoplasmic membrane of prokaryotes, ultimately resulting in cell wall degradation and cell lysis. However, there are more and more examples known for non-lytic holin-dependent secretion of proteins by bacteria, indicating that holins somehow can transport proteins without causing large membrane lesions. Phage-derived holins can be used for a non-lytic endolysin translocation to permeabilize the cell wall for the passage of secreted proteins. In addition, clostridia, which do not possess the Tat pathway for transport of folded proteins, most likely employ non-lytic holin-mediated transport also for secretion of toxins and bacteriocins that are incompatible with the general Sec pathway. The mechanism for non-lytic holin-mediated transport is unknown, but the recent finding that the small holin TpeE mediates a non-lytic toxin secretion in opened new perspectives. TpeE contains only one short transmembrane helix that is followed by an amphipathic helix, which is reminiscent of TatA, the membrane-permeabilizing component of the Tat translocon for folded proteins. Here we review the known cases of non-lytic holin-mediated transport and then focus on the structural and functional comparison of TatA and TpeE, resulting in a mechanistic model for holin-mediated transport. This model is strongly supported by a so far not recognized naturally occurring holin-endolysin fusion protein.

Citing Articles

Characteristics of the smallest brucellaphage with strong lytic ability.

Liu H, Zhong Y, Zhang Z, Xu K, Mao C, Yang Q Front Vet Sci. 2025; 12:1530123.

PMID: 39974167 PMC: 11836647. DOI: 10.3389/fvets.2025.1530123.

APC 4099 has broad-spectrum antimicrobial activity against both bacteria and fungi and produces several antimicrobial peptides, including the novel circular bacteriocin safencin E.

Kamilari E, OConnor P, Farias F, Johnson C, Buttimer C, Deliephan A Appl Environ Microbiol. 2025; 91(1):e0194224.

PMID: 39745440 PMC: 7617318. DOI: 10.1128/aem.01942-24.

Discovery and characterization of complete genomes of 38 head-tailed proviruses in four predominant phyla of archaea.

Xu T, Ni Y, Li H, Wu S, Yan S, Chen L Microbiol Spectr. 2024; 13(1):e0049224.

PMID: 39545734 PMC: 11705971. DOI: 10.1128/spectrum.00492-24.

Role of hypothetical protein PA1-LRP in antibacterial activity of endolysin from a new phage PA1.

Tian Y, Xu X, Ijaz M, Shen Y, Shahid M, Ahmed T Front Microbiol. 2024; 15:1463192.

PMID: 39507333 PMC: 11538084. DOI: 10.3389/fmicb.2024.1463192.

A Clostridioides difficile endolysin modulates toxin secretion without cell lysis.

Awad M, Suraweera C, Vidor C, Ye-Lin A, Williams G, Mileto S Commun Biol. 2024; 7(1):1044.

PMID: 39179651 PMC: 11344133. DOI: 10.1038/s42003-024-06730-4.

References

Anthony T, Chellappa G, Rajesh T, Gunasekaran P . Functional analysis of a putative holin-like peptide-coding gene in the genome of Bacillus licheniformis AnBa9. Arch Microbiol. 2009; 192(1):51-6. DOI: 10.1007/s00203-009-0530-7. View

Fritsch M, Krehenbrink M, Tarry M, Berks B, Palmer T . Processing by rhomboid protease is required for Providencia stuartii TatA to interact with TatC and to form functional homo-oligomeric complexes. Mol Microbiol. 2012; 84(6):1108-23. PMC: 3712462. DOI: 10.1111/j.1365-2958.2012.08080.x. View

Hu Y, Zhao E, Li H, Xia B, Jin C . Solution NMR structure of the TatA component of the twin-arginine protein transport system from gram-positive bacterium Bacillus subtilis. J Am Chem Soc. 2010; 132(45):15942-4. DOI: 10.1021/ja1053785. View

Orrell K, Melnyk R . Large Clostridial Toxins: Mechanisms and Roles in Disease. Microbiol Mol Biol Rev. 2021; 85(3):e0006421. PMC: 8483668. DOI: 10.1128/MMBR.00064-21. View

Garnier T, Cole S . Complete nucleotide sequence and genetic organization of the bacteriocinogenic plasmid, pIP404, from Clostridium perfringens. Plasmid. 1988; 19(2):134-50. DOI: 10.1016/0147-619x(88)90052-2. View

Erdmann J, Junemann J, Schroder A, Just I, Gerhard R, Pich A . Glucosyltransferase-dependent and -independent effects of TcdB on the proteome of HEp-2 cells. Proteomics. 2017; 17(15-16). DOI: 10.1002/pmic.201600435. View

Nonin-Lecomte S, Fermon L, Felden B, Pinel-Marie M . Bacterial Type I Toxins: Folding and Membrane Interactions. Toxins (Basel). 2021; 13(7). PMC: 8309996. DOI: 10.3390/toxins13070490. View

Hou B, Bruser T . The Tat-dependent protein translocation pathway. Biomol Concepts. 2015; 2(6):507-23. DOI: 10.1515/BMC.2011.040. View

Carvalho V, Prabudiansyah I, Kovacik L, Chami M, Kieffer R, van der Valk R . The cytoplasmic domain of the AAA+ protease FtsH is tilted with respect to the membrane to facilitate substrate entry. J Biol Chem. 2020; 296:100029. PMC: 7949044. DOI: 10.1074/jbc.RA120.014739. View

10.

Gautier R, Douguet D, Antonny B, Drin G . HELIQUEST: a web server to screen sequences with specific alpha-helical properties. Bioinformatics. 2008; 24(18):2101-2. DOI: 10.1093/bioinformatics/btn392. View

11.

Natale P, Bruser T, Driessen A . Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane--distinct translocases and mechanisms. Biochim Biophys Acta. 2007; 1778(9):1735-56. DOI: 10.1016/j.bbamem.2007.07.015. View

12.

Hodak H, Galan J . A Salmonella Typhi homologue of bacteriophage muramidases controls typhoid toxin secretion. EMBO Rep. 2012; 14(1):95-102. PMC: 3537140. DOI: 10.1038/embor.2012.186. View

13.

Wohlan K, Goy S, Olling A, Srivaratharajan S, Tatge H, Genth H . Pyknotic cell death induced by Clostridium difficile TcdB: chromatin condensation and nuclear blister are induced independently of the glucosyltransferase activity. Cell Microbiol. 2014; 16(11):1678-92. DOI: 10.1111/cmi.12317. View

14.

Kongari R, Rajaure M, Cahill J, Rasche E, Mijalis E, Berry J . Phage spanins: diversity, topological dynamics and gene convergence. BMC Bioinformatics. 2018; 19(1):326. PMC: 6139136. DOI: 10.1186/s12859-018-2342-8. View

15.

Bageshwar U, Musser S . Two electrical potential-dependent steps are required for transport by the Escherichia coli Tat machinery. J Cell Biol. 2007; 179(1):87-99. PMC: 2064739. DOI: 10.1083/jcb.200702082. View

16.

Walther T, Gottselig C, Grage S, Wolf M, Vargiu A, Klein M . Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism. Cell. 2013; 152(1-2):316-26. DOI: 10.1016/j.cell.2012.12.017. View

17.

Zhang Y, Hu Y, Li H, Jin C . Structural basis for TatA oligomerization: an NMR study of Escherichia coli TatA dimeric structure. PLoS One. 2014; 9(8):e103157. PMC: 4121141. DOI: 10.1371/journal.pone.0103157. View

18.

Burger S, Tatge H, Hofmann F, Genth H, Just I, Gerhard R . Expression of recombinant Clostridium difficile toxin A using the Bacillus megaterium system. Biochem Biophys Res Commun. 2003; 307(3):584-8. DOI: 10.1016/s0006-291x(03)01234-8. View

19.

Mitchell W . Carbohydrate assimilation by saccharolytic clostridia. Res Microbiol. 1992; 143(3):245-50. DOI: 10.1016/0923-2508(92)90016-h. View

20.

Tjalsma H, Antelmann H, Jongbloed J, Braun P, Darmon E, Dorenbos R . Proteomics of protein secretion by Bacillus subtilis: separating the "secrets" of the secretome. Microbiol Mol Biol Rev. 2004; 68(2):207-33. PMC: 419921. DOI: 10.1128/MMBR.68.2.207-233.2004. View