Proteomic analysis of clinical isolate of Stenotrophomonas maltophilia with blaNDM-1, blaL1 and blaL2 β-lactamase genes under imipenem treatment.
The co-occurrence of L1 and AmpR-L2 with bla(NDM-1) gene with an upstream 250-bp promoter was detected in a clinical isolate of  Stenotrophomonas maltophilia  DCPS-01, which was resistant to all β-lactams and sensitive only to colistin and fluoroquinolones. To investigate expression of resistance genes and the molecular mechanisms of bacteria resistance to carbapenems, proteomic profiles of the isolate was passaged with and without the drug by using 2D-PAGE. The results showed that 33 genes exhibiting a ≥3-fold change were identified as candidates that may help S. maltophilia survive drug selection. Strikingly, L1 was expressed more highly in cells grown with imipenem, and the abundant NDM-1 further increased, while very little L2 was detected even following induction. Specific activities for β-lactamase revealed that L2 remained at constitutive low levels (10.6 U/mg), while L1 and NDM-1 showed clear activity (69.8 U/mg). Our data support that imipenem could specifically and reversibly induce L1 and NDM-1, which together played key roles in drug resistance in DCPS-01. Although NDM-1 mediated resistance to carbapenems has been found in very few cases, to our knowledge, this is the first proteomics research of S. maltophilia with NDM-1, giving very broad-spectrum antibiotic resistance profiles.
Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
Wei
W
Liu
Dayang
D
Zou
Xuesong
X
Wang
XueLian
X
Li
Li
L
Zhu
Zhitao
Z
Yin
Zhan
Z
Yang
Xiao
X
Wei
Li
L
Han
Yufei
Y
Wang
Changlin
C
Shao
Simiao
S
Wang
Xiang
X
He
Dawei
D
Liu
Feng
F
Liu
Jie
J
Wang
Liuyu
L
Huang
Jing
J
Yuan
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D010641:Phenotype; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D020543:Proteome; D015378:Imipenem; D001618:beta-Lactamases