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

Josué Flores-Kim,Thomas G Bernhardt,David Z Rudner,Andrew Fenton,Genevieve S Dobihal

doi:10.7554/elife.44912

Josué Flores-Kim, Thomas G Bernhardt + Show 3 more

Open Access

https://doi.org/10.7554/elife.44912

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Abstract

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.

Highlights

Penicillin and related beta-lactams are some of our oldest and most effective antibiotics
Transposon libraries were prepared in a wild-type strain D39 without its capsule (WT) and a derivative deleted for lytA (DlytA) (Fenton et al, 2016; Land and Winkler, 2011)
When the insertion profiles were compared, we found that the gene tacL (SPD_1672) was virtually devoid of insertions in the WT library, but readily inactivated by insertions in the DlytA library (Figure 2A)

Summary

Introduction

Penicillin and related beta-lactams are some of our oldest and most effective antibiotics. They remodel the cell wall formed at the division site (septal PG) to shape the new poles and promote daughter cell separation (De Las Rivas et al, 2002; Fan, 1970; Heidrich et al, 2001; Hett et al, 2008; Lominski et al, 1958) Given their potential to induce cell lysis, it has long been appreciated that bacteria must possess robust mechanisms to control when and where PG hydrolases are activated to cut bonds in the PG network (Uehara and Bernhardt, 2011; Vollmer et al, 2008). We propose that changes in surface polymer assembly may underlie the mechanism of antibiotic-induced lysis for a number of other important Gram-positive pathogens

Results

Discussion

Materials and methods

Funding Funder National Institutes of Health