A proteomic analysis of penicillin resistance in Streptococcus pneumoniae reveals a novel role for PstS, a subunit of the phosphate ABC transporter.
Resistance to penicillin is widespread in the Gram-positive bacterium Streptococcus pneumoniae, and while several mutations are known to be implicated in resistance other mechanisms are likely to occur. We used a proteomic screen of two independent mutants in which resistance was selected in vitro. We found a number of differentially expressed proteins including PstS, a subunit of the phosphate ABC transporter of S. pneumoniae. This protein was increased in both mutants, a phenotype correlated to increased RNA expression of the entire phosphate ABC transporter operon. Inactivation of the pstS gene led to increased susceptibility to penicillin in the wild-type strain. To further link the expression of the ABC phosphate transporter with penicillin resistance, we looked at pstS mRNA levels in 12 independent clinical isolates sensitive and resistant to penicillin and found an excellent correlation between resistance and increased expression of pstS. Inactivation of pstS in one of the clinical isolates significantly reduced penicillin resistance. Global approaches are ideally suited for the discovery of novel factors in the biology of resistance.
Soualhine
Hafid
H
Centre de Recherche en Infectiologie et Division de Microbiologie, Faculté de Médecine, Université Laval, Quebec City, Canada.
Brochu
Vicky
V
Ménard
François
F
Papadopoulou
Barbara
B
Weiss
Karl
K
Bergeron
Michel G
MG
Légaré
Danielle
D
Drummelsmith
Jolyne
J
Ouellette
Marc
M
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000494:pharmacology; D028061:Phosphate Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020543:Proteome; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010406:Penicillins; D028061:Phosphate Transport Proteins; D020543:Proteome