WhyD tailors surface polymers to prevent bacteriolysis and direct cell elongation in Streptococcus pneumoniae

2022 ◽  
Author(s):  
Josué Flores-Kim ◽  
Genevieve S Dobihal ◽  
Thomas G Bernhardt ◽  
David Z Rudner
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Cell Elongation ◽  
Clinical Importance ◽  
Cell Wall Synthesis ◽  
Teichoic Acids ◽  
Direct Cell ◽  
Penicillin Treatment ◽  
Dramatic Shift ◽  
Lipoteichoic Acids

Penicillin and related antibiotics disrupt cell wall synthesis in bacteria and induce lysis by misactivating cell wall hydrolases called autolysins. Despite the clinical importance of this phenomenon, little is known about the factors that control autolysins and how penicillins subvert this regulation to kill cells. In the pathogen Streptococcus pneumoniae (Sp), LytA is the major autolysin responsible for penicillin-induced bacteriolysis. We recently discovered that penicillin treatment of Sp causes a dramatic shift in surface polymer biogenesis in which cell wall-anchored teichoic acids (WTAs) increase in abundance at the expense of lipid-linked lipoteichoic acids. Because LytA binds to these polymers, this change recruits the enzyme to its substrate where it cleaves the cell wall and elicits lysis. In this report, we identify WhyD (SPD_0880) as a new factor that controls the level of WTAs in Sp cells to prevent LytA misactivation and lysis. We show that WhyD is a WTA hydrolase that restricts the WTA content of the wall to areas adjacent to active PG synthesis. Our results support a model in which the WTA tailoring activity of WhyD directs PG remodeling activity required for proper cell elongation in addition to preventing autolysis by LytA.

scholarly journals A switch in surface polymer biogenesis triggers growth-phase-dependent and antibiotic-induced bacteriolysis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Josué Flores-Kim ◽  
Genevieve S Dobihal ◽  
Andrew Fenton ◽  
David Z Rudner ◽  
Thomas G Bernhardt
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Growth Phase ◽  
Exponential Growth ◽  
Cell Wall Synthesis ◽  
Phase Growth ◽  
Gram Positive ◽  
Osmotic Lysis ◽  
Penicillin Treatment ◽  
Lipoteichoic Acids

Penicillin and related antibiotics disrupt cell wall synthesis to induce bacteriolysis. Lysis in response to these drugs requires the activity of cell wall hydrolases called autolysins, but how penicillins misactivate these deadly enzymes has long remained unclear. Here, we show that alterations in surface polymers called teichoic acids (TAs) play a key role in penicillin-induced lysis of the Gram-positive pathogen Streptococcus pneumoniae (Sp). We find that during exponential growth, Sp cells primarily produce lipid-anchored TAs called lipoteichoic acids (LTAs) that bind and sequester the major autolysin LytA. However, penicillin-treatment or prolonged stationary phase growth triggers the degradation of a key LTA synthase, causing a switch to the production of wall-anchored TAs (WTAs). This change allows LytA to associate with and degrade its cell wall substrate, thus promoting osmotic lysis. Similar changes in surface polymer assembly may underlie the mechanism of antibiotic- and/or growth phase-induced lysis for other important Gram-positive pathogens.

scholarly journals Relation between Effects of Auxin on Cell Wall Synthesis and Cell Elongation

1965 ◽  
Vol 40 (2) ◽  
pp. 360-368 ◽  
Author(s):  
David B. Baker ◽  
Peter M. Ray
Keyword(s):  
Cell Wall ◽  
Cell Elongation ◽  
Cell Wall Synthesis

scholarly journals DivIVA Is Required for Polar Growth in the MreB-Lacking Rod-Shaped Actinomycete Corynebacterium glutamicum

2008 ◽  
Vol 190 (9) ◽  
pp. 3283-3292 ◽  
Author(s):  
Michal Letek ◽  
Efrén Ordóñez ◽  
José Vaquera ◽  
William Margolin ◽  
Klas Flärdh ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Corynebacterium Glutamicum ◽  
Chromosome Segregation ◽  
Polar Growth ◽  
Cell Wall Synthesis ◽  
Peptidoglycan Synthesis ◽  
Polarized Cell Growth

ABSTRACT The actinomycete Corynebacterium glutamicum grows as rod-shaped cells by zonal peptidoglycan synthesis at the cell poles. In this bacterium, experimental depletion of the polar DivIVA protein (DivIVACg) resulted in the inhibition of polar growth; consequently, these cells exhibited a coccoid morphology. This result demonstrated that DivIVA is required for cell elongation and the acquisition of a rod shape. DivIVA from Streptomyces or Mycobacterium localized to the cell poles of DivIVACg-depleted C. glutamicum and restored polar peptidoglycan synthesis, in contrast to DivIVA proteins from Bacillus subtilis or Streptococcus pneumoniae, which localized at the septum of C. glutamicum. This confirmed that DivIVAs from actinomycetes are involved in polarized cell growth. DivIVACg localized at the septum after cell wall synthesis had started and the nucleoids had already segregated, suggesting that in C. glutamicum DivIVA is not involved in cell division or chromosome segregation.

scholarly journals Decrease in Penicillin Susceptibility Due to Heat Shock Protein ClpL in Streptococcus pneumoniae

2011 ◽  
Vol 55 (6) ◽  
pp. 2714-2728 ◽  
Author(s):  
Thao Dang-Hien Tran ◽  
Hyog-Young Kwon ◽  
Eun-Hye Kim ◽  
Ki-Woo Kim ◽  
David E. Briles ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Synthesis Process ◽  
Resistant Bacteria ◽  
Mrna Levels ◽  
Cell Wall Synthesis ◽  
Content Type ◽  
Pulldown Assay

ABSTRACTAntibiotic resistance and tolerance are increasing threats to global health as antibiotic-resistant bacteria can cause severe morbidity and mortality and can increase treatment cost 10-fold. Although several genes contributing to antibiotic tolerance among pneumococci have been identified, we report here that ClpL, a major heat shock protein, could modulate cell wall biosynthetic enzymes and lead to decreased penicillin susceptibility. On capsular type 1, 2, and 19 genetic backgrounds, mutants lacking ClpL were more susceptible to penicillin and had thinner cell walls than the parental strains, whereas a ClpL-overexpressing strain showed a higher resistance to penicillin and a thicker cell wall. Although exposure ofStreptococcus pneumoniaeD39 to penicillin inhibited expression of the major cell wall synthesis genepbp2x, heat shock induced a ClpL-dependent increase in the mRNA levels and protein synthesized bypbp2x. Inducible ClpL expression correlated with PBP2x expression and penicillin susceptibility. Fractionation and electron micrograph data revealed that ClpL induced by heat shock is localized at the cell wall, and the ΔclpLshowed significantly reduced net translocation of PBP2x into the cell wall. Moreover, coimmunoprecipitation with either ClpL or PBP2x antibody followed by reprobing with ClpL or PBP2x antibody showed an interaction between ClpL and PBP2x after heat stress. This interaction was confirmed by His tag pulldown assay with either ClpLHis6or PBP2xHis6. Thus, ClpL stabilizedpbp2xexpression, interacted with PBP2x, and facilitated translocation of PBP2x, a key protein of cell wall synthesis process, contributing to the decrease of antibiotic susceptibility inS. pneumoniae.

scholarly journals The Pneumococcal Divisome: Dynamic Control of Streptococcus pneumoniae Cell Division

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicholas S. Briggs ◽  
Kevin E. Bruce ◽  
Souvik Naskar ◽  
Malcolm E. Winkler ◽  
David I. Roper
Keyword(s):  
Cell Wall ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Virulence Factors ◽  
Protein Complexes ◽  
Dynamic Control ◽  
Capsular Polysaccharides ◽  
Control Mechanisms ◽  
Cell Wall Synthesis ◽  
Molecular Events

Cell division in Streptococcus pneumoniae (pneumococcus) is performed and regulated by a protein complex consisting of at least 14 different protein elements; known as the divisome. Recent findings have advanced our understanding of the molecular events surrounding this process and have provided new understanding of the mechanisms that occur during the division of pneumococcus. This review will provide an overview of the key protein complexes and how they are involved in cell division. We will discuss the interaction of proteins in the divisome complex that underpin the control mechanisms for cell division and cell wall synthesis and remodelling that are required in S. pneumoniae, including the involvement of virulence factors and capsular polysaccharides.

Specific and spatial labeling of choline-containing teichoic acids in Streptococcus pneumoniae by click chemistry

2017 ◽  
Vol 53 (76) ◽  
pp. 10572-10575 ◽  
Author(s):  
A. M. Di Guilmi ◽  
J. Bonnet ◽  
S. Peiβert ◽  
C. Durmort ◽  
B. Gallet ◽  
...  
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Click Chemistry ◽  
Metabolic Pathway ◽  
Teichoic Acid ◽  
Teichoic Acids ◽  
First Time

A choline metabolic pathway was exploited to label for the first time teichoic acid (TA) in the Streptococcus pneumoniae cell wall.

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