NDLI: Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology

Content Provider	PubMed Central
Author	Raz, Assaf Tanasescu, Ana-maria Zhao, Anna M. Serrano, Anna Alston, Tricia Sol, Asaf Bachrach, Gilad Fischetti, Vincent A.
Editor	Roop, Roy Martin
Copyright Year	2015
Abstract	Cell wall anchored virulence factors are critical for infection and colonization of the host by Gram-positive bacteria. Such proteins have an N-terminal leader sequence and a C-terminal sorting signal, composed of an LPXTG motif, a hydrophobic stretch, and a few positively charged amino acids. The sorting signal halts translocation across the membrane, allowing sortase to cleave the LPXTG motif, leading to surface anchoring. Deletion of sortase prevents the anchoring of virulence factors to the wall; the effects on bacterial physiology however, have not been thoroughly characterized. Here we show that deletion of Streptococcus pyogenes sortase A leads to accumulation of sorting intermediates, particularly at the septum, altering cellular morphology and physiology, and compromising membrane integrity. Such cells are highly sensitive to cathelicidin, and are rapidly killed in blood and plasma. These phenomena are not a loss-of-function effect caused by the absence of anchored surface proteins, but specifically result from the accumulation of sorting intermediates. Reduction in the level of sorting intermediates leads to a return of the sortase mutant to normal morphology, while expression of M protein with an altered LPXTG motif in wild type cells leads to toxicity in the host environment, similar to that observed in the sortase mutant. These unanticipated effects suggest that inhibition of sortase by small-molecule inhibitors could similarly lead to the rapid elimination of pathogens from an infected host, making such inhibitors much better anti-bacterial agents than previously believed.
Related Links	http://dx.doi.org/10.1371/journal.pone.0140784
Starting Page	140784
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-10-20
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane

Crystal Structure of Spy0129, a Streptococcus pyogenes Class B Sortase Involved in Pilus Assembly

Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation

Necrotising fasciitis due to streptococcus pyogenes.

Differential Recognition of Surface Proteins in Streptococcus pyogenes by Two Sortase Gene Homologs

Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null Mutants

Crystal Structure of Spy0129, a Streptococcus pyogenes Class B Sortase Involved in Pilus Assembly

Mycobacterium tuberculosis Strains Lacking Surface Lipid Phthiocerol Dimycocerosate Are Susceptible to Killing by an Early Innate Host Response

Is Streptococcus pyogenes Resistant or Susceptible to Trimethoprim-Sulfamethoxazole?

Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology

Similar Documents

Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane

Crystal Structure of Spy0129, a Streptococcus pyogenes Class B Sortase Involved in Pilus Assembly

Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation

Necrotising fasciitis due to streptococcus pyogenes.

Differential Recognition of Surface Proteins in Streptococcus pyogenes by Two Sortase Gene Homologs

Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null Mutants

Crystal Structure of Spy0129, a Streptococcus pyogenes Class B Sortase Involved in Pilus Assembly

Mycobacterium tuberculosis Strains Lacking Surface Lipid Phthiocerol Dimycocerosate Are Susceptible to Killing by an Early Innate Host Response

Is Streptococcus pyogenes Resistant or Susceptible to Trimethoprim-Sulfamethoxazole?

Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology