Bactericidal effect of sulbactam against Acinetobacter baumannii ATCC 19606 studied by 2D-DIGE and mass spectrometry.
Acinetobacter baumannii has been associated with several severe hospital-acquired infections such as ventilator-associated pneumonia and meningitis. Sulbactam, a β-lactamase inhibitor, is usually combined with β-lactam antibiotics to treat infections. It has been found that sulbactam alone may be used to treat infections caused by A. baumannii, although the mechanism of the bactericidal effect remains unknown. In this study, proteomics was used to analyse protein intensity changes and to identify the proteins of A. baumannii following sulbactam treatment. In total, 54 proteins were found to exhibit significant changes in intensity. Proteins with reduced intensity included ATP-binding cassette (ABC) transporters as well as 30S and 50S ribosomal subunit proteins. These proteins are essential for nutrient import and protein synthesis and are vital for bacterial survival. The amplified proteins included glutamine synthetase, malic enzyme, RNA polymerase subunit α, and the molecular chaperones DnaK and GroEL, which function in metabolism, DNA and protein synthesis, and repair machinery. These amplified proteins were increased to rescue bacteria, however they could not overcome the effects of the reduced proteins and the bacteria were killed. This is the first report that the reduction of ABC transporters and 30S and 50S ribosomal subunit proteins plays an important role in the bactericidal effect of sulbactam against A. baumannii.
Department of Molecular Medicine and Institute of Life Science, National Tsing Hua University, Hsin-chu 30014, Taiwan.
Cheng-hao
CH
Lin
Department of Internal Medicine, Mackay Memorial Hospital, Hsin-chu, Taiwan. Electronic address: a4068@ms7.mmh.org.tw.
Shey-chiang
SC
Su
Department of Molecular Medicine and Institute of Life Science, National Tsing Hua University, Hsin-chu 30014, Taiwan.
Kun-hsuan
KH
Ho
Department of Internal Medicine, Mackay Memorial Hospital, Hsin-chu, Taiwan.
Yen-wei
YW
Hsu
Department of Molecular Medicine and Institute of Life Science, National Tsing Hua University, Hsin-chu 30014, Taiwan. Electronic address: krlee@mx.nthu.edu.tw.
Kuan-rong
KR
Lee
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D058977:Molecular Sequence Annotation; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D054681:Ribosome Subunits, Large, Bacterial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D054680:Ribosome Subunits, Small, Bacterial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013407:Sulbactam / Q000494:pharmacology*; D057825:Two-Dimensional Difference Gel Electrophoresis
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome; D012269:Ribosomal Proteins; D013407:Sulbactam
2D-DIGE; Acinetobacter baumannii; Antimicrobial; Mass spectrometry; Sulbactam