Thursday, May 14, 2015

Genetic analyses of PBP determinants in multidrug-resistant Streptococcus pneumoniae serogroup 19 CC320/271 clone with high level resistance to third generation cephalosporins.

Antimicrob Agents Chemother. 2015 Apr 27. pii: AAC.00094-15. [Epub ahead of print]
Genetic analyses of PBP determinants in multidrug-resistant Streptococcus pneumoniae serogroup 19 CC320/271 clone with high level resistance to third generation cephalosporins.
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Abstract
We describe the dissemination of a multidrug resistant serogroup 19 pneumococcal clone with representative MLST type ST271 with high level resistance to cefotaxime in Hong Kong, the penicillin binding protein genes (pbp) and their relationships to the Taiwan19F-14 (PMEN14) and the prevalent multidrug resistant clone, MDR19A-ST320. A total of 472 non-duplicate isolates in 2006 and 2011 were analyzed. Significant increases in the non-susceptibility rates of PEN (MIC ≥4.0 μg/ml, 9.9 vs 23.3%, p=0.0005), CTX (MIC ≥2.0 μg/ml, 12.2 vs 30.3%, p<0.0001, and meningitis MIC ≥1.0 μg/ml, 30.2 vs 48.7%, p=0.0001) and ERY (69.2 vs 84.0%, p=0.0003) were noted. The CTX resistant isolates with MIC 8 μg/ml in 2011 were of serotype 19F, belonging to ST271. Analyses of the PBP2x a.a. sequences in relation to the corresponding sequences of R6 strain revealed substitutions at M339F, E378A, M400T, and Y595F found within ST271 clone but not present in Taiwan19F-14 or MDR19A. In addition, the PBP2b of ST271 strains and that of Taiwan19F-14 clone were characterized by a unique a.a. substitution at E369D, while ST320 possessed unique a.a. substitution K366N as that of MDR19A in the United States. We hypothesize that ST271 originated from Taiwan19F-14 lineage which had disseminated in Hong Kong in early 2000s, and conferred higher β-lactam and cefotaxime resistance through acquisitions of 19 additional a.a. substitutions in PBP2b (a.a. positions 538 to 641) and altered PBP2x via recombination events. The serogroup 19 MDR CC320/271 clone warrants close monitoring to evaluate its effect after the switch to the expanded conjugate vaccines.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PMID: 25918136 [PubMed - as supplied by publisher] 

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