Heat-Shock Protein ClpL/HSP100 Increases Penicillin Tolerance in Streptococcus pneumoniae

Author(s):  
Thao Dang-Hien Tran ◽  
Hyog-Young Kwon ◽  
Eun-Hye Kim ◽  
Ki-Woo Kim ◽  
David E. Briles ◽  
...  
2017 ◽  
Vol 7 (1) ◽  
Author(s):  
José Lourenço ◽  
Eleanor R. Watkins ◽  
Uri Obolski ◽  
Samuel J. Peacock ◽  
Callum Morris ◽  
...  

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 ◽  
...  

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.


2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A152-A152
Author(s):  
H SUZUKI ◽  
S NAGAHASHI ◽  
M MIYAZAWA ◽  
M MORI ◽  
H NAGATA ◽  
...  

2004 ◽  
Vol 171 (4S) ◽  
pp. 203-203
Author(s):  
Cecilia Sarto ◽  
Paolo Favini ◽  
Cristina Valsecchi ◽  
Stefano Casellato ◽  
Fulvio Magni ◽  
...  

2003 ◽  
Vol 2 (1) ◽  
pp. 13
Author(s):  
L JANOSKUTI ◽  
A ZSARY ◽  
Z FORHECZ ◽  
K KELTAI ◽  
T FENYVESI ◽  
...  

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