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Breaking barriers :
Breaking barriers : pCF10 type 4 secretion system relies on a self-regulating muramidase to modulate the cell wall
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- Sun, Wei-Sheng (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Umeå Centre for Microbial Research (UCMR)
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- Torrens, Gabriel (författare)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- ter Beek, Josy (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå Centre for Microbial Research (UCMR),Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
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- Cava, Felipe (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)
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- Berntsson, Ronnie P.-A. (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Umeå Centre for Microbial Research (UCMR)
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(creator_code:org_t)
- American Society for Microbiology, 2024
- 2024
- Engelska.
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 15:8
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Conjugative type 4 secretion systems (T4SSs) are the main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. To deliver the DNA substrate to recipient cells, it must cross the cell envelopes of both donor and recipient bacteria. In the T4SS from the enterococcal conjugative plasmid pCF10, PrgK is known to be the active cell wall degrading enzyme. It has three predicted extracellular hydrolase domains: metallo-peptidase (LytM), soluble lytic transglycosylase (SLT), and cysteine, histidine-dependent amidohydrolases/peptidases (CHAP). Here, we report the structure of the LytM domain and show that its active site is degenerate and lacks the active site metal. Furthermore, we show that only the predicted SLT domain is functional in vitro and that it unexpectedly has a muramidase instead of a lytic transglycosylase activity. While we did not observe any peptidoglycan hydrolytic activity for the LytM or CHAP domain, we found that these domains downregulated the SLT muramidase activity. The CHAP domain was also found to be involved in PrgK dimer formation. Furthermore, we show that PrgK interacts with PrgL, which likely targets PrgK to the rest of the T4SS. The presented data provides important information for understanding the function of Gram-positive T4SSs.IMPORTANCE: Antibiotic resistance is a large threat to human health and is getting more prevalent. One of the major contributors to the spread of antibiotic resistance among different bacteria is type 4 secretion systems (T4SS). However, mainly T4SSs from Gram-negative bacteria have been studied in detail. T4SSs from Gram-positive bacteria, which stand for more than half of all hospital-acquired infections, are much less understood. The significance of our research is in identifying the function and regulation of a cell wall hydrolase, a key component of the pCF10 T4SS from Enterococcus faecalis. This system is one of the best-studied Gram-positive T4SSs, and this added knowledge aids in our understanding of horizontal gene transfer in E. faecalis as well as other medically relevant Gram-positive bacteria. Antibiotic resistance is a large threat to human health and is getting more prevalent. One of the major contributors to the spread of antibiotic resistance among different bacteria is type 4 secretion systems (T4SS). However, mainly T4SSs from Gram-negative bacteria have been studied in detail. T4SSs from Gram-positive bacteria, which stand for more than half of all hospital-acquired infections, are much less understood. The significance of our research is in identifying the function and regulation of a cell wall hydrolase, a key component of the pCF10 T4SS from Enterococcus faecalis. This system is one of the best-studied Gram-positive T4SSs, and this added knowledge aids in our understanding of horizontal gene transfer in E. faecalis as well as other medically relevant Gram-positive bacteria.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Type 4 Secretion System
- cell wall
- Gram-positive bacteria
- pCF10
- integrated structural biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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