Biology:SaPI

From HandWiki
Short description: Mobile genetic element in the genome of S. aureus

SaPIs (Staphylococcus aureus  pathogenicity islands) are a family of ~15 kb mobile genetic elements resident in the genomes of the vast majority of S. aureus strains.[1][2] Much like bacteriophages, SaPIs can be transferred to uninfected cells and integrate into the host chromosome. Unlike the bacterial viruses, however, integrated SaPIs are mobilized by host infection with "helper" bacteriophages (specific SaPIs may require specific helper bacteriophages for mobilization, though Staphylococcus phage 80alpha appears to mobilize all known SaPIs). SaPIs are used by the host bacteria to co-opt the phage reproduction cycle for their own genetic transduction and also inhibit phage reproduction in the process.[2]

SaPIs can infect many strains that are resistant to phages and can readily be transferred to Listeria monocytogenes even though staphylococcal phages cannot grow in Listeria cells.[3] SaPIs occur infrequently in other staphylococcal species, but SaPI-like elements are common and widespread in other Gram-positive cocci.[4]

Mechanism

SaPI DNA is maintained in a prophage-like state under the control of a master repressor and is induced to excise and replicate by helper phages encoding proteins that counter the SaPI repressor.[5] One set of SaPIs is induced  by other co-resident SaPIs which must first be induced by helper phages, setting up a 3-way cascade[6] For most SaPIs, following replication, concatemeric SaPI DNA is packaged by the headful mechanism, utilizing a small terminase subunit (TerS) encoded by the SaPI[7] in phage-like particles that are released in numbers approaching 109/ml by phage-induced lysis.[8] A subset of SaPIs have acquired a cos site and use the phage’s TerS for packaging by the cos  mechanism.[9]' The released SaPI particles infect other staphylococcal cells, injecting their DNA which integrates into a specific chromosomal attachment site[10] of which there are 5 in S. aureus.[10] SaPIs are ancestrally related to Siphoviridae and possess phage-related genes enabling their integration/excision, replication, and packaging.[2] They lack structural phage proteins and lysis proteins and utilize those of the helper phage , which they modify to form small capsids commensurate with their genomes.

Function

Their evolutionary divergence from an ancestral prophage has involved not only the loss of structural and lytic proteins, but also the development (or acquisition) of several different means of partially blocking reproduction of their helper phages.[11][12] These phage interference functions are advantageous both to the host cell, as they (partially) block predation by exogenous phages, and to the SaPI, as they enable it to keep pace with helper phage reproduction. Unlike the CRISPRs, which simply destroy infecting phages and thus totally block phage-mediated horizontal gene transfer (HGT), the SaPIs  are major agents of phage–dependent HGT, as they only partially block phage reproduction and also package chromosomal fragments as well as their own genomes.[13]

Role in pathogenicity

SaPIs were discovered on the basis of their carriage of the gene for toxic shock syndrome toxin-1 and they are uniquely responsible for staphylococcal toxic shock. They also carry other superantigen toxins as well as other virulence factors among which is a set of genes enabling their host strains to coagulate farm animal blood plasma. These genes encode different alleles of a coagulase, the von Willebrand factor-binding protein, which has a role in determining the animal host specificity of S. aureus.[14] The toxin and other accessory genes are expressed by the integrated and repressed SaPI genomes, as are the toxin genes of converting prophages.

Conversion to antibacterial agents

One of the original SaPIs, SaPI2, has been converted to a non-antibiotic therapeutic agent for the treatment of staphylococcal and listerial infections.[15] This conversion involved the removal of all toxin and other virulence genes, and of the capsid morphogenesis genes, and the addition, by cloning, of antibacterial genes including those encoding CRISPR/cas9 with spacers targeting conserved chromosomal genes. These cause a lethal double-stranded DNA cleavage in the target protospacer. Alternative cargos include CRISPR/dcas9 with spacers targeting and inhibiting genes that regulate bacterial virulence, or the gene for lysostaphin, a powerful staphylolytic enzyme.[16] The production of these transformed SaPI2s, known as antibacterial drones (ABDs), is greatly enhanced by deleting the helper prophage’s terS gene so that only ABD DNA is packaged.[7] The ABDs cure experimental staph infections in mice and are being further developed for clinical use. To preclude the development of resistance, ABDs for potential clinical use will always contain at least two different antibacterial modules that act by different mechanisms.

References

  1. ↑ "The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus". Molecular Microbiology 29 (2): 527–43. July 1998. doi:10.1046/j.1365-2958.1998.00947.x. PMID 9720870. 
  2. ↑ 2.0 2.1 2.2 "The phage-related chromosomal islands of Gram-positive bacteria". Nature Reviews. Microbiology 8 (8): 541–51. August 2010. doi:10.1038/nrmicro2393. PMID 20634809. 
  3. ↑ "Phage-mediated intergeneric transfer of toxin genes". Science 323 (5910): 139–41. January 2009. doi:10.1126/science.1164783. PMID 19119236. Bibcode: 2009Sci...323..139C. 
  4. ↑ "Phage-inducible islands in the Gram-positive cocci". The ISME Journal 11 (4): 1029–1042. April 2017. doi:10.1038/ismej.2016.163. PMID 27959343. 
  5. ↑ "Phage dUTPases control transfer of virulence genes by a proto-oncogenic G protein-like mechanism". Molecular Cell 49 (5): 947–58. March 2013. doi:10.1016/j.molcel.2012.12.013. PMID 23333307. 
  6. ↑ "A regulatory cascade in SaPI activation". Nature Microbiology in press. 2020. 
  7. ↑ 7.0 7.1 "Specificity of staphylococcal phage and SaPI DNA packaging as revealed by integrase and terminase mutations". Molecular Microbiology 72 (1): 98–108. April 2009. doi:10.1111/j.1365-2958.2009.06634.x. PMID 19347993. 
  8. ↑ "Molecular genetics of SaPI1--a mobile pathogenicity island in Staphylococcus aureus". Molecular Microbiology 41 (2): 365–77. July 2001. doi:10.1046/j.1365-2958.2001.02488.x. PMID 11489124. 
  9. ↑ "Staphylococcal pathogenicity island DNA packaging system involving cos-site packaging and phage-encoded HNH endonucleases". Proceedings of the National Academy of Sciences of the United States of America 111 (16): 6016–21. April 2014. doi:10.1073/pnas.1320538111. PMID 24711396. Bibcode: 2014PNAS..111.6016Q. 
  10. ↑ 10.0 10.1 "The SaPIs: mobile pathogenicity islands of Staphylococcus". Chemical Immunology and Allergy (Basel) 93: 42–57. 2007. doi:10.1159/000100857. ISBN 978-3-8055-8266-7. PMID 17369699. 
  11. ↑ "Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism". Proceedings of the National Academy of Sciences of the United States of America 109 (40): 16300–5. October 2012. doi:10.1073/pnas.1204615109. PMID 22991467. Bibcode: 2012PNAS..10916300R. 
  12. ↑ "Precisely modulated pathogenicity island interference with late phage gene transcription". Proceedings of the National Academy of Sciences of the United States of America 111 (40): 14536–41. October 2014. doi:10.1073/pnas.1406749111. PMID 25246539. Bibcode: 2014PNAS..11114536R. 
  13. ↑ "Pathogenicity island-directed transfer of unlinked chromosomal virulence genes". Molecular Cell 57 (1): 138–49. January 2015. doi:10.1016/j.molcel.2014.11.011. PMID 25498143. 
  14. ↑ "Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI-carried variants of von Willebrand factor-binding protein". Molecular Microbiology 77 (6): 1583–94. September 2010. doi:10.1111/j.1365-2958.2010.07312.x. PMID 20860091. 
  15. ↑ "Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice". Nature Biotechnology 36 (10): 971–976. November 2018. doi:10.1038/nbt.4203. PMID 30247487. 
  16. ↑ "Cloning, sequence, and expression of the lysostaphin gene from Staphylococcus simulans". Proceedings of the National Academy of Sciences of the United States of America 84 (5): 1127–31. March 1987. doi:10.1073/pnas.84.5.1127. PMID 3547405. Bibcode: 1987PNAS...84.1127R. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:SaPI&oldid=3593370"